WO2017019833A1 - Compositions containing repair cells and cationic dyes - Google Patents

Compositions containing repair cells and cationic dyes Download PDF

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WO2017019833A1
WO2017019833A1 PCT/US2016/044395 US2016044395W WO2017019833A1 WO 2017019833 A1 WO2017019833 A1 WO 2017019833A1 US 2016044395 W US2016044395 W US 2016044395W WO 2017019833 A1 WO2017019833 A1 WO 2017019833A1
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PCT/US2016/044395
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French (fr)
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Emma MCCULLAGH
Sebastian Bernales
David Hung
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Medivation Technologies, Inc.
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Publication of WO2017019833A1 publication Critical patent/WO2017019833A1/en

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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/0006Modification of the membrane of cells, e.g. cell decoration
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/69Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6901Conjugates being cells, cell fragments, viruses, ghosts, red blood cells or viral vectors

Definitions

  • FIG. 1 Photomicrographs demonstrating formation of Raj i cell pellets after incubation with 10 uM Compound 20 for 1, 5, 15, or 30 minutes.
  • FIGS. 2A-B Stability of Raj i cell pellets after incubation with 1 ⁇ or 10 ⁇ , ⁇
  • FIG. 2A 30 minute incubation.
  • FIG. 2B 5 minute incubation.
  • FIGS. 3A-B Photomicrographs demonstrating chondrogenic differentiation of rat bone marrow-derived mesenchymal stem cells (MSCs) after 21 days in chondrogenic medium.
  • FIG. 3A without Compound 20.
  • FIG. 3B in the presence of 10 ⁇ Compound 20.
  • FIGS. 4A-D Photomicrographs demonstrating chondrogenic differentiation of rabbit MSCs in pellet cultures.
  • FIG. 4A rabbit MSCs incubated in chondrogenic medium without Compound 20.
  • FIG. 4B rabbit MSCs incubated in chondrogenic medium with Compound 20.
  • FIG. 4C rabbit MSCs incubated in basal medium without Compound 20.
  • FIG. 4D rabbit MSCs incubated in basal medium with Compound 20.
  • FIGS. 5A-B Photomicrographs demonstrating chondrogenic differentiation in pellet cultures of 100,000 rabbit MSCs after 21 days.
  • FIG. 5A rabbit MSCs incubated in chondrogenic medium without Compound 20.
  • FIG. SB rabbit MSCs incubated in chondrogenic medium with Compound 20.
  • FIG. 6. Graph demonstrating qualitative analysis of targeting of Raji cells stained with Compound 20 on different tissues.
  • FIG. 7 Photomicrographs demonstrating targeting of rabbit mesenchymal stem ceils (rbMSCs) incubated with Compound 20 to different organs from Balb/c mice,
  • FIG. 8A Photomicrographs demonstrating that Compound 4 promotes adherence of Raji cells to meniscus expiants.
  • FIG. 8B Photomicrographs demonstrating that Compound 4 and Compound 20 (FIG. 3B) promote cell adherence of Raji cells to meniscus expiants.
  • FIG. 9 Photomicrographs demonstrating the presence of Compound 4 in the knees of rats up to 24 hours after intra-articular injection.
  • FIGS. 10A-B Photomicrographs demonstrating that Compound 4 stains the small intestine (FIG. 10A) but not Peyer's patches (FIG. 10B) after oral administration.
  • FIGS. 11A-11B Photomicrographs demonstrating the location of safranin-0 and
  • FIG. 11 A thymus, liver, heart, lung.
  • FIG. 11B spleen, small intestine.
  • FIGS. 1.2A-12B Photomicrographs demonstrating the location of Compound 4 staining in in various tissues 24 hours after intravenous administration.
  • FIG. 12A spleen, heart, kidney, brain.
  • FIG. 12B liver, lung, bladder, blood.
  • Aryl refers to an unsaturated aromatic carbocyclic group having a single ring (e.g., phenyl) or multiple condensed rings (e.g., naphthyl or anthryl) which condensed rings may or may not be aromatic.
  • the aryl group contains from 6 to 14 annular carbon atoms (e.g., 6-14, 6-13, 6-12, 6-1 1, 6- 0, 6-9, 6-8, 6-7, 7-14, 7-13, 7- 2, 7-1 1, 7-10, 7-9, 7-8, 8-14, 8- 13, 8-12, 8- 1 1, 8- 10, 8-9, 9-14, 9-13, 9-12, 9-1 1, 9-10, 10-14, 10-13, 10- 12, 10-1 1, 1 14, 1 1-13, 1 1 -12, 12-14, 12-13, 13-14, 6, 7, 8, 9, 10, 1 1 , 12, 13, or 14).
  • An aryl group having more than one ring where at least one ring is non-aromatic may be connected to the parent structure at either an aromatic ring position or at a non-aromatic ring position .
  • an aryl group having more than one ring where at least one ring is non-aromatic is connected to the parent structure at an aromatic ring position.
  • Heteroaryl refers to an unsaturated aromatic carbocyclic group having from 2 to 10 annular carbon atoms (e.g., 2-10, 2-9, 2-8, 2-7, 2-6, 2-5, 2-4, 2-3, 3-10, 3-9, 3-8, 3-7, 3-6, 3-5, 3- 4, 4-10, 4-9, 4-8, 4-7, 4-6, 4-5, 5-10, 5-9, 5-8, 5-7, 5-6, 6- 10, 6-9, 6-8, 6-7, 7- 10, 7-9, 7-8, 8-10, 8-9, 9-10, 2, 3, 4, 5, 6, 7, 8, 9, or 10) and at least one annular heteroatom, including but not limited to heteroatoms such as nitrogen, oxygen and sulfur.
  • annular carbon atoms e.g., 2-10, 2-9, 2-8, 2-7, 2-6, 2-5, 2-4, 2-3, 3-10, 3-9, 3-8, 3-7, 3-6, 3-5, 3- 4, 4-10, 4-9, 4-8, 4-7, 4-6, 4-5, 5-10,
  • a heteroaryl group may have a single ring (e.g., pyridyl, furyl) or multiple condensed rings (e.g., indolizinyl, benzothienyl) which condensed rings may or may not be aromatic.
  • a heteroaryl group having more than one ring where at least one ring is non-aromatic may be connected to the parent structure at either an aromatic ring position or at a non-aromatic ring position.
  • a heteroaryl group having more than one ring where at least one ring is non-aromatic is connected to the parent structure at an aromatic ring position.
  • Cycloalkyl is a saturated cyclic hydrocarbon structure and can consist of one ring, such as cyclohexyl, or multiple rings, such as adamantyl.
  • a cycloalkyl comprising more than one ring may be fused, spiro or bridged, or combinations thereof.
  • a cycloalkyl can be a saturated cyclic hydrocarbon having from 3 to 13 annular carbon atoms (e.g., 3-13, 3-12, 3-1 1 , 3-10, 3-9, 3-8, 3- 7, 3-6, 3-5, 3-4, 4-13, 4- 12, 4-1 1, 4-10, 4-9, 4-8, 4-7, 4-6, 4-5, 5- 13, 5-12, 5-1 1, 5-10, 5-9, 5-8, 5- 7, 5-6, 6-13, 6-12, 6-1 1, 6-10, 6-9, 6-8, 6-7, 7-13, 7-12, 7-1 1 , 7-10, 7-9, 7-8, 8- 13, 8-12, 8-1 1 , 8-
  • cycloal kyl groups include adamantyl,
  • decahydronaphthalenyl cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.
  • Heterocyclyl refers to a saturated or an unsaturated non-aromatic group having a single ring or multiple condensed rings, and having from I to 10 annular carbon atoms (e.g., 1- 10, 1-9, 1-8, 1-7, 1 -6, 1-5, 1 -4, 1-3, 1 -2, 2-10, 2-9, 2-8, 2-7, 2-6, 2-5, 2-4, 2-3, 3-10, 3-9, 3-8, 3-7, 3-6, 3- 5, 3-4, 4-10, 4-9, 4-8, 4-7, 4-6, 4-5, 5-10, 5-9, 5-8, 5-7, 5-6, 6- 10, 6-9, 6-8, 6-7, 7-10, 7-9, 7-8, 8- 10, 8-9, 9-10, 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10) and from 1 to 4 annular heteroatoms (e.g., 1-4, 1 -3, 1- 2, 2-4, 2-3, 3-4, 1, 2, 3, o4 5), such as nitrogen, sulfur or oxygen
  • a heterocycle comprising more than one ring may be fused, spiro or bridged, or any combination thereof.
  • one or more of the rings can be aryl or heteroaryl.
  • a heterocycle having more than one ring where at least one ring is aromatic may be connected to the parent structure at either a non- aromatic ring position or at an aromatic ring position.
  • a heterocycle having more than one ring where at least one ring is aromatic is connected to the parent structure at a non-aromatic ring position.
  • R a and 3 ⁇ 4 (or R aj and 3 ⁇ 4i; or R a2 and Rt> 2 ; or
  • R a and Rj means “R a and Rj, (or R aJ and Rt>i; or R a2 and Rj, 2 ; or ⁇ and ; or Rc 2 and Ry),
  • R a and 3 ⁇ 4 or R a i and 3 ⁇ 4j; or R a2 and Rj >2 ; or ⁇ and Rx; or p
  • R ⁇ and Rv are ' 3 ⁇ 4 ⁇ -" " means "R a and j, (or R ai and ⁇ ; or R a2 and R3 ⁇ 4 2 ; or R ⁇ and Rx; or R ⁇
  • a "repair cell” as used herein includes cells which, when exposed to appropriate conditions, differentiate into an appropriate cell type for repair of a particular target tissue, as well as cells which are at least partially differentiated into the appropriate cell type for the tissue to be repaired.
  • a repair cell differentiates into a ceil which produces and secretes components needed to repair an injury to a joint (e.g., hyaline cartilage, tendon, meniscus).
  • a repair cell is a chondrocyte.
  • a repair cell is a mesenchymal stem cell (MSC).
  • MSCs Methods of obtaining, culturing, and expanding populations of MSCs are well known in the art. See, e.g., US 2004/0009157; US 2012/0148548; U.S. Patent 5,486,359; and U.S. Patent 5,226,914.
  • autologous MSCs are used.
  • allogenic MSCs are used (e.g., MSCs obtained from banks of umbilical cord MSCs, MHC-matched MSCs, or MSCs engineered to not have comprise immunogenic MHCs).
  • a population of repair cells e.g., M SCs
  • a compound which is a cationic dye multimer described below
  • the population is subjected to centrifugation to form a pellet composition.
  • a "pellet composition” as used herein, unless otherwise specified, does not imply that the pelleted have been cultured in vitro (as in the optional culture step disclosed below).
  • a cationic dye multimer such as compound 4 or compound 20
  • these conditions include incubation with the compound at room temperature for 1, 5, 15, or 30 minutes.
  • Conditions for other compounds disclosed herein can readily be determined using the working examples as a starting point.
  • the repair cells e.g., MSCs
  • repair cells e.g., MSCs
  • a cationic dye multimer e.g., compound 4 or compound 20
  • about 10 5 repair cells e.g., MSCs
  • a cationic dye multimer e.g., compound 4 or compound
  • Pellet cultures of MSCs are known in the art (e.g., US 2003/0026786; US 2005/0019865; Bosnakovski et al., Experimental Hematology 32, 502-09, 2004; Chen et al., PLoS One 9, e9156I, 1-11, 2014; Miyanashi et al., Tissue Engineering 12, 1419-28, 2006; Ong et al.,
  • the pellet is not cultured before applying the pellet to the site of the injury. In some variations, the pellet is cultured for varying periods of time before applying the pellet to the site of the injury, as described in the paragraphs below,
  • the pellet is cultured for 1-21 days, 1 -20 days, 1-19 days, 1 -18 days, 1-17 days, 1-16 days, 1-15 days, 1-14 days, 1-13 days, 1-12 days, 1-11 days, 1-10 days, 1-9 days, 1-8 days, 1-7 days, 1-6 days, 1 -5 days, 1-4 days, 1 -3 days, or 1-2 days. In some variations, the pellet is cultured for less than 1-21 days, 1-20 days, 1-19 days, 1-18 days, 1-17 days, 1-16 days, 1-15 days, 1-14 days, 1-13 days, 1-12 days, 1-1 1 days, 1 -10 days, 1-9 days, 1-8 days, 1-7 days,
  • the pellet is cultured for 2-21 days, 2-20 days, 2-19 days, 2-18 days,
  • the pellet is cultured for less than 2-21 days, 2-20 days, 2-19 days, 2-18 days, 2-17 days, 2-16 days, 2-15 days, 2-14 days, 2-13 days, 2-12 days, 2-11 days, 2-10 days, 2-9 days, 2-8 days, 2-7 days, 2-6 days, 2-5 days, 2-4 days, or 2-3 days.
  • the pellet is cultured for less than 2-21 days, 2-20 days, 2-19 days, 2-18 days, 2-17 days, 2-16 days, 2-15 days, 2-14 days, 2-13 days, 2-12 days, 2-11 days, 2-10 days, 2-9 days, 2-8 days, 2-7 days, 2-6 days, 2-5 days, 2-4 days, or 2-3 days.
  • the pellet is cultured for 3-21 days, 3-20 days, 3-19 days, 3-18 days, 3-17 days, 3-16 days, 3-15 days, 3-14 days, 3-13 days, 3-12 days, 3-11 days, 3-10 days, 3-9 days,
  • the pellet is cultured for less than for 3-21 days, 3-20 days, 3-19 days, 3-18 days, 3-17 days, 3-16 days, 3-15 days, 3-14 days, 3-13 days, 3-12 days, 3-11 days, 3-10 days, 3-9 days, 3-8 days, 3-7 days, 3-6 days, 3-5 days, or 3-4 days.
  • the pellet is cultured for 4-21 days, 4-20 days, 4-19 days, 4-18 days,
  • the pellet is cultured for less than 4- 21 days, 4-20 days, 4-19 days, 4-18 days, 4-17 days, 4-16 days, 4-15 days, 4-14 days, 4-13 days,
  • the pellet is cultured for 5-21 days, 5-20 days, 5-19 days, 5-18 days,
  • the pellet is cultured for less than 5-21 days, 5-16 days, 5-15 days, 5-14 days, 5-13 days, 5-12 days, 5-1 1 days, 5-10 days, 5-9 days, 5-8 days, 5-7 days, or 5-6 days.
  • the pellet is cultured for less than 5-21 days,
  • the pellet is cultured for 6-21 days, 6-20 days, 6-19 days, 6-18 days,
  • the pellet is cultured for less than 6-21 days, 6-20 days,
  • the pellet is cultured for 7-21 days, 7-20 days, 7-19 days, 7-18 days,
  • the pellet is cultured for less than for 7-21 days, 7-20 days, 7-19 days, 7-18 days, 7-17 days, 7-16 days, 7-15 days, 7-14 days, 7-13 days, 7-12 days, 7-1 1 days, 7- 10 days, 7-9 days, or 7-8 days.
  • the pellet is cultured for 8-21 days, 8-20 days, 8-19 days, 8-18 days,
  • the pellet is cultured for less than 8-21 days, 8-20 days, 8-19 days, 8-18 days, 8-17 days, 8-16 days, 8-15 days, 8-14 days, 8-13 days, 8-12 days, 8-11 days, 8-10 days, or 8-9 days [17] In some variations, the pellet is cultured for 9-21 days, 9-20 days, 9-19 days, 9-18 days, 9-17 days, 9-16 days, 9-15 days, 9-14 days, 9-13 days, 9-12 days, 9-1 1 days, or 9-10 days. In some variations, the pellet is cultured for less than for 9-21 days, 9-20 days, 9-19 days, 9-18 days, 9-17 days, 9-16 days, 9-15 days, 9-14 days, 9-13 days, 9-12 days, 9-1 1 days, or 9-10 days. In some variations, the pellet is cultured for less than for 9-21 days, 9-20 days, 9-19 days, 9-18 days, 9-17 days, 9-16 days, 9-15 days, 9-14 days, 9-13 days, 9-12 days, 9-11 days, or 9-10 days.
  • the pellet is cultured for 10-21 days, 10-20 days, 10-19 days, 10-18 days, 10-17 days, 10-16 days, 10-15 days, 10-14 days, 10-13 days, 10-12 days, or 10-11 days. In some variations, the pellet is cultured for less than 10-21 days, 10-20 days, 10-19 days, 10-18 days, 10-17 days, 10-16 days, 10-15 days, 10-14 days, 10-13 days, 10-12 days, or 10-1 1 days.
  • the pellet is cultured for 11-21 days, 1 1-20 days, 11-19 days, 11-18 days, 1 1-17 days, 1 1 -16 days, 11-15 days, 11-14 days, 1 1 -13 days, or 11-12 days. In some variations, the pellet is cultured for less than 11-21 days, 11-20 days, 1 1-19 days, 11-18 days, 11- 17 days, 11-16 days, 11-15 days, 1 1 -14 days, 11-13 days, or 1 1 -12 days,
  • the pellet is cultured for 12-21 days, 12-20 days, 12-19 days, 12-18 days, 12-17 days, 12-16 days, 12-15 days, 12-14 days, or 12-13 days. In some variations, the pellet is cultured for less than 2-21 days, 12-20 days, 12-19 days, 12-18 days, 12-17 days, 12-16 days, 12-15 days, 12-14 days, or 12-13 days.
  • the pellet is cultured for 13-21 days, 13-20 days, 13-19 days, 13- 8 days, 13-17 days, 13-16 days, 13-15 days, or 13-14 days. In some variations, the pellet is cultured for less than 13-21 days, 13-20 days, 13-19 days, 13-18 days, 13-17 days, 13-16 days, 13-15 days, or 13-14 days.
  • the pellet is cultured for 14-21 days, 14-20 days, 14-19 days, 14-18 days, 14-17 days, 14-16 days, or 14-15 days. In some variations, the pellet is cultured for less than 14-21 days, 14-20 days, 14-19 days, 14-18 days, 14-17 days, 14-16 days, or 14-15 days,
  • the pellet is cultured for 15-21 days, 15-20 days, 15-19 days, 15-18 days, 15-17 days, or 15-16 days. In some variations, the pellet is cultured for less than 15-21 days, 15-20 days, 15-19 days, 1 5-18 days, 15-17 days, or 15-16 days.
  • the pellet is cultured for 16-21 days, 16-20 days, 16-19 days, 16-18 days, or 16-17 days. In some variations, the pellet is cultured for less than 16-21 days, 16-20 days, 16-19 days, 16-18 days, or 16-17 days. [25] In some variations, the pellet is cultured for 17-21 days, 17-20 days, 17-19 days, or 17-18 days. In some variations, the pellet is cultured for less than 17-21 days, 17-20 days, 17-19 days, or 17-18 days,
  • the pellet is cultured for 18-21 days, 18-20 days, or 18-19 days. In some variations, the pellet is cultured for less than 18-21 days, 18-20 days, or 18-19 days.
  • the pellet is cultured for 19-21 days or 19-20 days. In some variations, the pellet is cultured for less than 19-21 days or 19-20 days.
  • the pellet is cultured for 20-21 days. In some variations, the pellet is cultured for less than 20-21 days.
  • the peilet is cultured for 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 21, or 21 days. In some variations, the pellet is cultured for less than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 21 , or 21 days.
  • the culture medium does not comprise TGF .
  • the culture medium compri ses TGFp.
  • the culture medium is a basal culture medium.
  • the culture medium is a chondrocyte differentiation medium.
  • this disclosure also provides methods of differentiating MSCs in pellet cultures which do not require the use of chondrogenic medium or ⁇ . See example B5, below.
  • Pellet compositions comprising repair ceils can be used to treat injured or diseased tissues, including, but not limited to, pancreas, kidney, intestine (e.g., small intestine, cecum), heart, cartilage (e.g., trachea, femoral cartilage), thymus, liver, brain, bladder, blood. Administration of a Pellet Composition to the Site of a Cartilage Injury
  • Administration of one or more pellet compositions of MSCs can be carried out during an arthroscopic or open joint procedure and can be used to treat cartilage injuries at joints such as the acromioclavicular, carpometacarpal (finger or thumb), coracoclavicular, humeroulnar, humeroradial, radioulnar (distal, intermedial, proximal), intermetacarpal, interphalangeal, metacarpophalangeal, midcarpal, radiocarpal, shoulder, sternoclavicular, wrist,
  • cartilage injuries at joints such as the acromioclavicular, carpometacarpal (finger or thumb), coracoclavicular, humeroulnar, humeroradial, radioulnar (distal, intermedial, proximal), intermetacarpal, interphalangeal, metacarpophalangeal, midcarpal, radiocarpal, shoulder, sternoclavicular, wrist,
  • Types of cartilage injuries which can be treated include damage to cartilage at a synovial joint occurring as a result of mechanical destruction due to trauma or progressive degeneration (osteoarthrosis; wear and tear) or associated with a disease or disorder, such as osteoarthritis, rheumatoid arthritis, gout, reactive arthritis, psoriatic arthritis, or juvenile arthritis.
  • Other injuries include damage to tendons, ligaments, and the meniscus.
  • tissue engineering, including stem cell therapy, to treat such injuries has been reviewed. See, e.g. Nesic, ei ai. "Cartilage Tissue Engineering for Degenerative Joint Disease," Advanced Drug Delivery Reviews (2006), 58(2): 300-322; Johnstone, et al.
  • Pellet compositions can be provided in a pharmaceutical composition comprising a pharmaceutically acceptable carrier.
  • a "pharmaceutically acceptable carrier” carrier is a material that is not biologically or otherwise undesirable, e.g., the material may be incorporated into a pharmaceutical composition administered to an individual without causing significant undesirable biological effects or interacting in a deleterious manner with any of the other components of the composition in which it is contained.
  • Pharmaceutically acceptable carriers meet the required standards of toxicological and manufacturing testing and/or are included on the Inactive Ingredient Guide prepared by the U.S. Food and Drug administration.
  • the compounds depicted herein by virtue of their cationic nature, are typically present as salts even if salts are not depicted and thus are accompanied by a pharmaceutically acceptable counterion, forming a pharmaceutically acceptable salt.
  • a "pharmaceutically acceptable counterion” is an ionic portion of a salt that is not toxic when released from the salt upon administration to a recipient.
  • Pharmaceutically acceptable salts may be formed with many acids, including but not limited to hydrochloric, sulfuric, acetic, lactic, malic, succinic, hydrogen bisulfide, salicylic, tartaric, bitartaric, ascorbic, maleic, besylic, fumaric, gluconic, glucuronic, formic, glutamic, methanesulfonic, ethanesulfonic, benzenesuifonic, lactic, oxalic, para- bromophenylsulfonic, carbonic, succinic, citric, benzoic and acetic acid, and related inorganic and organic acids.
  • Such pharmaceutically acceptable counterions thus include sulfate, pyrosulfate, bi sulfate, sulfite, bisulfate, phosphate, monohydrogenphosphate,
  • tautomeric forms may be present for any of the compounds described herein, each and every tautomeric form is intended even though only one or some of the tautomeric forms may be explicitly depicted.
  • the tautomeric forms specifically depicted may or may not be the predominant forms in solution or when used according to the methods described herein.
  • Cationic dye multimers can be linear, branched, or cyclic.
  • a catiomc dye multimer is a dimer, in which two cationic dye moieties are linked with a linker as described below.
  • a cationic dye multimer is a trimer or higher order multimer containing, e.g., 3, 4, or 5 cationic dye moieties joined in various configurations by linkers such that the multimer is linear, branched, or cyclic.
  • the cationic dye moieties in a multimer, as well as the linkers can be the same or different, in various combinations, as set forth in the description below.
  • the binding capacity of a cationic dye multimer can be tuned based on the polarity /electron density of the charged multimer system such that, for example, the cationic dye multimer exhibits differential binding affinities to, e.g., cartilage and MSCs.
  • linker moieties comprise a multivalent, rigid or non-rigid, alky] chain containing appropriate functionality at the termini to bond with the cationic dye moieties, as also set forth in the description below.
  • linkers could, for example, comprise a bivalent chain thus having a cationic dye at each end resulting in a dimer.
  • Other combinations and configurations are similarly described herein,
  • cationic dyes which can be used to make catiomc dye multimers as described herein have a planar tri-aromatic core with the potential to have a positive charge at physiological pH. Representative examples of such cationic dyes are shown below, with the "wiggle line" indicating one possible point of attachment to a linker to a dimer or higher oligomer:
  • cationic dyes such as safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue are unreactive. These amino groups can however be functionalized through reactions that provide "handles" which comprise a carboxyhc acid or an amine; cationic dyes comprising such handles are referred to herein as "cationic dye moieties,"
  • 3J-diamino-2,6-dimethyl-5-phenylphenazin-5-ium 3J-diamino-2,8-dimethyl-5-phenylphenazin-5-ium wherein as presented here a methyl group can be at the 6- or 8-position.
  • Commercially available sources of such reagents can comprise a mixture of such regioisomers. All compounds presented herein encompass any and all derivatives from such regioisomeric dyes.
  • Cationic dye moieties can be functionalized with the appropriately substituted linkers described below using reactions known to those skilled in the art; this is illustrated for safranin-0 in the schematic below:
  • cationic dye multimers in which at least one of the cationic dye multimers is safranin-O, the pendant phenyl ring of the safranin-0 is unsubstituted.
  • the pendant phenyl ring of the safranin-O is substituted with 1-3 (e.g., 1-3, 1-2, I, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. Examples of electron-donating groups include— H 2 ,— HR,— R 2 ,— OH,— O " ,
  • R is C 1 -C6 linear or branched aikyi (e.g., C 1-C6, C 1-C5, C1-C4, C1-C3, C 1-C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched aikyi).
  • electron-withdrawing groups include— -NO 2 ,— NR 3 + , halo (e.g.
  • R is C1-C6 linear or branched alkyl (e.g. , C 1-C6, C 1-C5, C 1-C4, C 1-C3, CI-C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4- C5, C4, C5-C6, C5, or C6 linear or branched alkyl).
  • R is C1-C6 linear or branched alkyl (e.g. , C 1-C6, C 1-C5, C 1-C4, C 1-C3, CI-C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4- C5, C4, C5-C6, C5, or C6 linear or branched alkyl).
  • linkers comprise a positive charge, which can be provided by a positive charged substituent such as an amino al ky] , amino heterocyclyl, or N-containing heteroaromatic group.
  • positively charged linkers comprise amino acids such as Lys, Arg, or His, If a rigid linker is desired, one or more aromatic rings, cycloalkyl rings, heteroaromatic rings, or heterocyclyl rings, can be used to provide rigidity.
  • Linkers which can be used in cationic dye multimers include linkers (a), (a. l), (a.2), (b), (b. l), (c), (c. l), (c.2), (d), (e), (e. l), (f), (f. l), (f.2), (g), (g. l), (g.2), (h), (h.
  • n 1-6, nj is 1-4, and each * is an attachment site for a cationic dye moiety ; ⁇ 3 ⁇ ⁇ , in which ⁇ is 1-6, « / is 1 -4, and * is an attachment site for a cationic dye moiety:
  • n is 1-6, n ⁇ is 1-4, and * is an attachment site for cationic dy ⁇ moiety; , in which n is 0-6, tij is 1-4, and each * is an attachment site for a cationic dye moiety; , in which n is 0-6, n ⁇ is 1-4, and * is an attachment site for cationic dye moiety, , in which n is 0-6; rt is 1 -4; for each independent instance of R a and
  • R and Rj independently are H or CH 3 , or (2) R a and 3 ⁇ 4 are or O
  • n is 0-6; n ⁇ is 1-4; for each independent instance of R a and
  • R a and R 3 ⁇ 4 independently are H or CH or (2) R a and R 3 ⁇ 4 are ' 3 ⁇ 4 or and * is an attachment site for a cationic dye moiety,
  • R a and R3 ⁇ 4 are - ⁇ or '3 ⁇ 4 f- , or (3) two of CRaRb are ; and each * is an attachment site for a cationic dye moiety;
  • n is 0-6, 3 ⁇ 4/ is 1-4, and each * is an attachment site for a cationic dye moiety;
  • n ⁇ 0-5, n 2 is 1-5 and * is an attachment site for a cationic dye moiety
  • n 2 is 1-5 and each * is an attachment site for a cationic dye moiety
  • nj is 0-5, n 2 is 1-5, and each * is an attachment site for a cationic dye moietv;
  • nj is 0-5, n? is 1-5, and * is an attachment site for a cationic dye moiety
  • n t and n 2 independently are 1 -5 and * is an attachment site for a cationic dye moiety
  • n 2 is 1-5 and each * is an attachment site for a cationic dye moiety
  • n 2 is 1-5 and * is an attachment site for a
  • n 2 is 1-5 and * is an attachment site for a cationic dye moiety:
  • R ai and 3 ⁇ 4i independently are H or CH 3 , or (2) R a! and w independently are or (3) two of CR a iR 3 ⁇ 4 i for each independent instance of a 2 and Rj>2, a z and j,? (1) independently are H or CH 3 or (2) R a2 and R b2 independently are or or (3) two of are
  • each * is an attachment site for a cationic dye moiety
  • ring A is aryl, heteroaryl, cycloalkyl, or heterocycfyl; for each independent instance of a i and R M , R a ⁇ and j,i (1) independently are H or CH 3 ,
  • >i independently are " L or ' 3 ⁇ 4 , or (3) two of CRaiR b i are ' ⁇ t ⁇ f or eac h Independent instance of R a2 and Rj,?, a2 and Rt> 2 ( I )
  • R a2 and j, 2 independently are " 3 ⁇ 4 3 ⁇ 4s " or ' fc ⁇ or (3) two of CR a 2Rj,2 are ⁇ 3 ⁇ 4 , for each independent instance of R c i and 3 ⁇ 4 ⁇ , R c i and ⁇ n (1) independently are H or CH 3 , or (2) ⁇ and R ⁇ ii independently are
  • ring A i iss aarryyl, . heteroaryl, cycloalkyl, or heterocyclyl; for each independent instance of R ai and RM, R nd R b i 1) independently ar or CH 3 , or (2) R ai and j,i independently ar :ee or (3) two of CR at R *ji are
  • Ra2 and Rj>2 1 (1) independently are H or
  • R ⁇ and Rai independently are ' 3 ⁇ 4 or " ⁇ - or (3) two of C cj f j ! are 3 ⁇ 4 ; for each independent instance of and 3 ⁇ 4?, R nd d 2 (1) independently are H or CH 3 , or (2) R ⁇ and R i!2 independently are
  • R a i and 3 ⁇ 4 ⁇ (1) independently are H or CH 3 or (2)
  • R al and R bi independently are or (3) two of CR a iR w are
  • a2 and R&2 (1) independently are H or C3 ⁇ 4, or (2) R a2 and R&2 independently are " 3 ⁇ 4 ⁇ -* or
  • R C 2 and (1) independently are H or CH 3 ,
  • n 0-6, n ⁇ is 1-4, and each * is an
  • n 0-6, n ⁇ is 1-4, and * is an attachment site for a cationic dye moiety:
  • n 2 is 1-5 and each * is an attachment site for a cationic dye moiety:
  • n 2 is 1-5 and * is an attachment site for a cationic dye moiety
  • ni 0-5
  • n 2 is 1-5
  • «j is 0-5
  • * is the attachment site for a cationic dye moiety.
  • This disclosure also provides cationic dye moieties which comprise one or more linkers, which are suitable for preparing the conjugates and the cationic dimers disclosed herein.
  • Cationic dyes useful for these embodiments include, but are not limited to, safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue. In some
  • the cationic dye moiety is present as a monomer. In other embodiments, the cationic dye moiety is present as a multimer. In either of these embodiments, the cationic dye moiety comprises one or more linkers, which may be the same or different. Suitable linkers include, but are not limited to, linkers (a), (a. l), (a.2), (b), (b. I), (c), (c. l), (c.2), (d), (e), (e. l), (f), (f. l), (f.2), (g), (g. l), (g.2), (h), (h. l), (h,2), (i), (i. l), (i.2), (j), (j . l), (j 2), (k), (1), (1, 1), (1.2), (m), (m. l), (n), (n. l ), (n.2), (o), (p), (q), (r), and (s), described above.
  • each of Dl and D2 is a cationic dye moiety, n is 1-6, and « / is 1.-4.
  • Dl and D2 are different cationic dye moieties.
  • Dl and D2 are the same cationic dye moiety.
  • Dl and D2 independently are selected from the group consisting of safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue.
  • n is 1-6, 1-5, 1-4, 1- 3, 1-2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, 5-6, I, 2, 3, 4, 5, or 6.
  • n ⁇ is 1 -4, 1-3, 1 -2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
  • Dl is safranin-O.
  • D2 is safranin-O.
  • Dl and D2 are safranin-O.
  • the pendant phenyl ring of Dl is unsubstituted.
  • the pendant phenyl ring of Dl is substituted with 1-3 (e.g., 1-3, 1-2, 1, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring.
  • the substituents are selected independently from— -NH 2 ,— NHR,— NR 2 ,— OH,— O " ,
  • R is C 1-C6 linear or branched alkyl (e.g., C1-C6, C 1-C5, C1-C4, C 1-C3, C1-C2, C I , C2-C6, C2-C5, C2-
  • the substituents are selected independently from— -NO 2 ,— - R 3 + , halo (e.g., F, Br, CI, I), trihaiide
  • R is C1-C6 linear or branched al kyl (e.g., C 1 -C6, C1-C5, C 1 -C4, C 1 -C3, C l-
  • the pendant phenyl ring of 1)2 is unsubstituted.
  • the pendant phenyl ring of D2 is substituted with 1-3 (e.g., 1-3, 1 -2, 1, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring.
  • the substituents are selected independently from— NH 2 ,— NHR,— NR 2 ,— OH,— O " ,
  • R is C1-C6 linear or branched aikyi (e.g., C1-C6, C 1-C5, C1-C4, C 1-C3, C 1-C2, C I, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched aikyi).
  • C1-C6 linear or branched aikyi e.g., C1-C6, C 1-C5, C1-C4, C 1-C3, C 1-C2, C I, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched aikyi).
  • the substituents are selected independently from— -N0 2 ,— -NR 3 + , halo (e.g., F, Br, CI, I), trihaiide (e.g., --CF 3 , --CCI3, --CBr 3 ,—CI3),— CN, --SO3H,—COOH,—COOR, --CHO, and —COR, wherein R is C1-C6 linear or branched alkyl (e.g., C 1 -C6, C1-C5, C 1 -C4, C 1-C3, Cl- C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
  • halo e.g., F, Br, CI, I
  • trihaiide e.g., --CF 3 , --CCI
  • n is 0-6, and n ⁇ is 1-4.
  • Dl and D2 are different cationic dye moieties. In other variations of formula (2), Dl and D2 are the same cationic dye moiety. In some variations of formula (2), Dl and 1)2 are independently selected from the group consisting of safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue.
  • n is 0-6, 0-5, 0-4, 0- 3, 0-2, 0-1 , 1-6, 1-5, 1-4, 1-3, 1 -2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, 5-6, 0, I, 2, 3, 4, 5, or 6.
  • n ⁇ is 1-4, 1 -3, 1-2, 2-4, 2-3, 3-4, 1 , 2, 3, or 4,
  • Dl is safranin-O.
  • D2 is safranin-O.
  • Dl and D2 are safranin-O.
  • the pendant phenyl ring of Dl is unsubstituted.
  • the pendant phenyl ring of Dl is substituted with 1-3 ⁇ e.g., 1-3, 1-2, 1, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring.
  • the pendant phenyl ring of Dl is substituted, the
  • substituents are selected independently from— NH 2 ,— NHR,— NR 2 ,— OH,— O " ,
  • R is C1-C6 linear or branched aikyi ⁇ e.g., C1-C6, C 1-C5, C1-C4, C1-C3, C1-C2, CI, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched aikyi).
  • the substituents are selected independently from— -N0 2 ,— -N 3 + , halo ⁇ e.g., F, Br, CI, I), trihalide ⁇ e.g.,— CF 3 , CCk— CBr 3 , Ch i.— CN, --SO3H,—COOH,— COOR,—CHO, and — COR, wherein R is C1-C6 linear or branched aikyi ⁇ e.g., C 1-C6, C1-C5, C1-C4, C 1-C3, Cl- C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
  • the pendant phenyl ring of D2 is unsubstituted.
  • the pendant phenyl ring of D2 is substituted with 1-3 ⁇ e.g., 1-3, 1 -2, 1, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring.
  • the pendant phenyl ring of D2 is substituted, the
  • substituents are selected independently from— NH 2 ,— NHR,— NR 2 ,— OH,— O " ,
  • R is C1-C6 linear or branched alkyl (e.g., C1 -C6, C 1 -C5, C1 -C4, C 1 -C3, C1 -C2, C I, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl).
  • C1-C6 linear or branched alkyl e.g., C1 -C6, C 1 -C5, C1 -C4, C 1 -C3, C1 -C2, C I, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl.
  • the substituents are selected independently from— 0 2 ,— ⁇ , halo (e.g., F, Br, CI, I), trihaiide (e.g.,— CF 3 ,— CC1 3 ,— CBr 3 ,— CI 3 ),— CN, SO 1 I,— COOH,— COOR,— CHO, and —COR, wherein R is C1-C6 linear or branched alkyl (e.g., C 1-C6, C1-C5, C 1-C4, C 1-C3, C I - C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
  • halo e.g., F, Br, CI, I
  • trihaiide e.g.,— CF 3 ,— CC
  • each of Dl and D2 is a cationic dye moiety
  • n is 0-6, and ti is 1-4
  • R a and R 3 ⁇ 4 independently are
  • R a and R b are " 3 ⁇ 4 or ' 3 ⁇ 4 * ⁇ t or (3) two of CR a R b are " 3 ⁇ 4 - .
  • Dl and D2 are different cationic dye moieties.
  • Dl and 1)2 are the same cationic dye moiety.
  • Dl and D2 are independently selected from the group consisting of safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue.
  • n is 0-6, 0-5, 0-4, 0- 3, 0-2, 0-1 , 1-6, 1-5, 1-4, 1-3, 1 -2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, 5-6, 0, I, 2, 3, 4, 5, or 6.
  • n ⁇ is 1-4, 1 -3, 1-2, 2-4, 2-3, 3-4, 1 , 2, 3, or 4,
  • each of R a i and R i is H and R a2 and 3 ⁇ 42 are ' 3 ⁇ 4 ⁇ ⁇ " ⁇
  • each of R a i and b i is CH 3 and R a2 and b2 are " 3 ⁇ 4 ⁇ .
  • each of R a i and R b i is CH 3 and R a2 and R 1(2 are ⁇ 2 - .
  • R b i is CH 3
  • R a2 and b2 are ' 3 ⁇ 4 .
  • R a iii is 2
  • R a i and 3 ⁇ 4i are 3 ⁇ 4 ' 3 ⁇ 4A ⁇
  • R a 2 and 3 ⁇ 4 2 are 1 ⁇ 4 ⁇ £
  • each of R a i,R i, R a2 , R b2 , R a s, and b is CH 3 .
  • n ⁇ is 3, each of Rai,Rbi, R a 2, and b j, is H and each of R a3 and b3 is CH 3 .
  • each of R a i,Rbi, a 2, and R b2 is II and ⁇ and R 3 are ⁇ .
  • each of R a i,Rt>i, R ⁇ , and R b2 is CH 3 and R a3 and Rb3 are ' ⁇ - .
  • R a i is H and each of R a2 , R b i, and R b2 is CH 3 , and A 3 and Rb3 are " ⁇ - .
  • each of R a i and R a2 is H and each of Rw and R b2 is CH 3 , and R a3 and Rb3 are .
  • each of R a j,R b i, R a 2, and R b2 is H and ⁇ and Rb3 are ' 3 ⁇ 4 ⁇ ⁇ .
  • ni 3
  • R a i is H and each of R ⁇ , R b i, and Rb2 is CH 3 , and a 3 and Rb3 are ⁇ .
  • n ⁇ 3
  • Rj,i and R 2 is CH 3
  • R a s and R3 ⁇ 43 are ' 3 ⁇ 4 ⁇ .
  • R a i and R3 ⁇ 4i are ' 3 ⁇ 4 R a2 and and each of R 3 ⁇ 4 3 and Rj, 3 is H.
  • R al and M are " L
  • R a2 and Rb2 are and each of a 3 and j,3 is CH 3 .
  • R 3 ⁇ 42 and 3 ⁇ 42 are " ⁇ - , a 3 is H
  • R b i are ' 3 ⁇ 4 a 2 and . b2 are ' * ⁇ and each of ⁇ and ⁇ is H.
  • R ai and R b i are " 3 ⁇ 4 , . a2 and
  • Riii and M are " v 3 ⁇ 4 v R a2 and 2 are 1 ⁇ 4 '3 ⁇ 4 ⁇ £ and each of as and 3 is H.
  • R a! and R 3 ⁇ 4 j are " 3 ⁇ 4 ⁇ * , A 2
  • R b2 are , and each of R a s and sis CH 3 .
  • R a i and i are and each of and 3 is H. In some variations of
  • R b2 are * 3 ⁇ 4 X ⁇ " ⁇ , and each of and sis CH 3 .
  • n ⁇ is 3
  • R AJ and i are '3 ⁇ 4 aa and 2 are U '3 ⁇ 4 -U * ⁇
  • R A 3 is H
  • bsis CH 3 is 3
  • each of Rai,Rbi, Ra2, Rb2, a3, 3 ⁇ 43, a4, and 3 ⁇ 44 is CH 3 .
  • each of Rai, ex, a2 , R3 ⁇ 42, a , and R ⁇ is H and each of A 4 and R ⁇ is CH 3 .
  • each of Rai, Rbi, R a 2, and 2 is H and each of Ra3, R*3 , A4 , and 4 is CH 3 .
  • each of Rai, Rbi, Ra2, 3 ⁇ 4 2 , R a s, and ⁇ i s CH 3 and each of A4 and 3 ⁇ 44 is H.
  • each of R a i,Ra2, and A 3 is H and each of Rbi, ⁇ , and j, 3 is CH 3 .
  • R a i is H
  • RM is CH 3
  • each of Ra2, R 2, Ra3. and Rj>3 is CH 3 .
  • R a i is H
  • i is CH 3
  • each of R a2 , Rb 2 , Ra3, and 3 ⁇ 43 is H.
  • each of R ai and R a2 is H
  • each of Rw and Rb 2 is CH 3
  • each of R a s and Rb3 is H.
  • rij is 4
  • each of R ai and R a2 is H
  • each of w and Rt> 2 is CH 3
  • each of R a3 and R 3 ⁇ 43 is CH 3 .
  • Ra2 and R3 ⁇ 42 are H, R a3 and R 3 ⁇ 43 are CH 3 , and R A4 and RM are .
  • n,- 4, a i and M are H, R a2 and j>2 are CH 3 , aj and Rt>3 are CH 3 , and R a4 and 3 ⁇ 44 are " ⁇ - .
  • R a i and R ⁇ are CH 3 , 3 2 and 3 ⁇ 42 are CH 3
  • R a3 and 3 ⁇ 4 3 are CH 3 , and R A4 and R M are "
  • R a2 and R b2 are CH 3 , R a3 and Rj, 3 are and R a4 and M are " ⁇ - .
  • R ai and jji are CH 3 , and R b2
  • R aj is H
  • RJ,J is CH 3
  • R a2 and Rj, 2 are CH 3
  • l b3 are " 3 ⁇ 4 and Rj, 4 and 3 ⁇ 44 are ' 3 ⁇ 4 ⁇
  • R AS is H
  • M is CH 3
  • R A2 is H
  • R b2 is CH 3
  • R A and R 1(3 R a4 and Rj, 4 are ' 3 ⁇ 4 .
  • R A2 and 3 ⁇ 4 2 are "* ⁇ R A and R 1(3 are " ⁇ - and A 4 and R3 ⁇ 44 are ,
  • R AI and M are are Ra3 and I3 ⁇ 4 3 are , and
  • a 4 and i> 4 are [85]
  • R b i are H
  • R a2 and Rj> 2 are H
  • R a3 and I3 ⁇ 43 are H
  • R 3 ⁇ 4 and I M are 1 ⁇ 4 " *A ⁇ .
  • R a2 and j, 2 are H, R a3 and Rt> 3 are CH 3 , and R a4 and R i i are " ⁇ - .
  • R ai and Rj,i are H, R a2 and j, 2
  • R A 3 and 3 ⁇ 43 are CH 3
  • a 4 and R3 ⁇ 44 are
  • R b i are H
  • R a2 and Ri, 2 are H
  • R a3 and 3 ⁇ 4>3 are ' 3 ⁇ 4 ⁇ ⁇
  • R a 4 and Rb4 are v.
  • Ra2 and (, 2 are CH 3 , R a3 and Rj,3 are '3 ⁇ 4 and R A 4 and &4 are "3 ⁇ 4 ⁇
  • R ai and ⁇ i are CH 3 , ⁇ and R b2
  • R a3 and j, 3 are and R a4 and j> 4 are ⁇
  • R a ⁇ is H
  • R a2 and 3 ⁇ 4> 2 are ⁇
  • R a3 and K B3 are ⁇
  • R a4 and R b4 are 3 ⁇ 4 .
  • R a i is H
  • R i is
  • Rb2 are f ⁇
  • R A3 and B 3 are ' 3 ⁇ 4A ⁇ ⁇
  • R A4 and M are "l A f ⁇
  • Rj,2 are H
  • R a3 and B 3 are CH 3
  • R A 4 and R b4 are ' 1 ⁇
  • R b i are ⁇ R a2 and R b2 are ⁇ ⁇
  • R a3 and R b3 are f"
  • R a4 and R M are '3 ⁇ 4 ⁇ 4 .
  • R ⁇ and ⁇ ⁇ are II, R ⁇ and ⁇ are CH 3 , and R a a and R 3 and A and j,4 together are " ⁇ ⁇ V in some variations of formula (3) described in the paragraphs above in which ⁇ , ⁇ is 4, R a ⁇ and a 2 are H,
  • Rex and j,2 are ( ⁇ f and a s and j,3 and A 4 and R3 ⁇ 44 together are x .
  • R b i are H
  • Ra2 and j,2 are ' 3 ⁇ 4 ⁇ and a j and 3 ⁇ 43 and A 4 and ⁇ together are .
  • rij is 4, R A! and & j O
  • R A2 and s, 2 are CH 3
  • a 3 and Rj,3 and R A 4 and Rj,4 together are ' ⁇ ⁇ .
  • R a i is H
  • R 3 ⁇ 4 i is
  • R a2 and Rj, 2 are '3 ⁇ 4 A '
  • R A3 and R B3 and R A4 and B 4 together are x V
  • R a3 b i and R a 2 and R b 2 together are - and Raj and RM and A 4 and R B 4 together are
  • Dl is safranin-O.
  • 1)2 is safranin-O.
  • Dl and D2 are safranin-O.
  • the pendant phenyl ring of Dl is unsubstituted.
  • the pendant phenyl ring of Dl is substituted with 1-3 (e.g., 1-3, 1 -2, 1, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring.
  • the substituents are selected independently from— NH 2 ,— -NHR,— NR 2 ,— OH,— O " ,
  • R is C 1-C6 linear or branched alkyl (e.g., C 1 -C6, C 1 -C5, C 1 -C4, C 1 -C3, C1 -C2, C I, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl).
  • C 1 -C6, C 1 -C5, C 1 -C4, C 1 -C3, C1 -C2, C I, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl e.g., C 1 -C6, C 1 -C5, C 1 -C4, C 1 -C3, C1 -C
  • the substituents are selected independently from— N0 2 ,— R 3 + , halo (e.g. , F, Br, CI, I), trihalide (e.g. ,— CF 3 ,— CCI3,— CBr 3 , ( ' !
  • R is C1-C6 linear or branched alkyl (e.g., C 1-C6, C1-C5, C 1-C4, C 1-C3, Cl - C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
  • C1-C6 linear or branched alkyl e.g., C 1-C6, C1-C5, C 1-C4, C 1-C3, Cl - C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl.
  • the pendant phenyl ring of D2 is unsubstituted.
  • the pendant phenyl ring of 1)2 is substituted with 1-3 (e.g., 1-3, 1 -2, 1, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring.
  • the pendant phenyl ring of D2 is substituted, the
  • substituents are selected independently from— NH 2 ,— -NHR,— -NR 2 ,— OH,— O " ,
  • R is C1-C6 linear or branched alkyl (e.g., C1 -C6, C1-C5, C1-C4, C1 -C3, C1-C2, CI, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl).
  • C1-C6 linear or branched alkyl e.g., C1 -C6, C1-C5, C1-C4, C1 -C3, C1-C2, CI, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl.
  • the substituents are selected independently from— N0 2 ,— R 3 + , halo (e.g., F, Br, CI, I), trihaiide (e.g., CF 3 , --CCI3, --CBr 3 , --CI3),— CN, -- SO3H, --COOH,—COOR,—CHO, and — COR, wherein R is C1-C6 linear or branched alkyl (e.g., C 1-C6, C1-C5, C1-C4, C 1-C3, CI- C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
  • halo e.g., F, Br, CI, I
  • trihaiide e.g., CF 3 , --CCI3, --CBr 3
  • R a and R b independently are H or
  • R a and R b are " 3 ⁇ 4 or ' 3 ⁇ 4 ? or (3) two of CR a R b are " ,
  • Dl and D2 are different cationic dye moieties.
  • Dl and 1)2 are the same cationic dye moiety.
  • Dl and D2 are independently selected from the group consisting of safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue.
  • k is 2-10, 2-9, 2-8, 2-7, 2-6, 2-5, 2-4, 2-3, 3-10, 3-9, 3-8, 3-7, 3-6, 3-5, 3-4, 4-10, 4-9, 4-8, 4-7, 4-6, 4-5, 5-10, 5-9, 5- 8, 5-7, 5-6, 6-10, 6-9, 6-8, 6-7, 7-10, 7-9, 7-8, 8-10, 8-9, 9-10, 2, 3, 4, 5, 6, 7, 8, 9, or 10.
  • each R a is H and each R b is H. In some variations of formula (4) described in the paragraphs above, each R a is H and each Rj, is CH 3 . In some variations of formula (4) described in the paragraphs above, each R a and R & is . In some variations of formula (4) described in the paragraphs above, each O
  • each of R a and R 3 ⁇ 4 is H, and the remaining occurrences of R a and R 3 ⁇ 4 are as defined above for formula (4).
  • each of R a and R b in a first occurrence of R a and R b , each of R a and is CH 3 , and the remaining occurrences of R a and i, are as defined above for formula (4).
  • a first R a is H
  • the remaining occurrences of Ra and R b are as defined above for formula (4).
  • R a and 3 ⁇ 4 are examples of formula (4) described in the paragraphs above.
  • R a and 3 ⁇ 4 are ⁇ and the remaining occurrences of R a and R b are as defined above for formula (4).
  • each of R a and Rj> is H, and the remaining occurrences of R a and 3 ⁇ 4 are as defined above for formula (4).
  • each of R a and R 3 ⁇ 4 is CH 3 , and the remaining occurrences of R a and Ri, are as defined above for formula (4).
  • R b , R a and 3 ⁇ 4 are and the remaining occurrences of R a and 3 ⁇ 4 are as defined above for formula (4).
  • each of R a and Rj in three occurrences of R a and R b , is H, and the remaining occurrences of R a and 3 ⁇ 4 are as defined above for formula (4).
  • each of R a and Ri in three occurrences of R a and , each of R a and is CH 3 , and the remaining occurrences of R a and Ri» are as defined above for formula (4).
  • each of R a and b is H, and the remaining occurrences of R a and 3 ⁇ 4 are as defined above for formula (4).
  • each of R a and R b is CH 3 , and the remaining occurrences of R a and b are as defined above for formula (4).
  • R b , R a and b and the remaining occurrences of R a and b are as defined above for formula (4).
  • each of R a and R b is H, and the remaining occurrences of R a and R are as defined above for formula (4).
  • each of R a and R is CH 3 , and the remaining occurrences of R a and b are as defined above for formula (4).
  • R b , R a and j, are and the remaining occurrences of R a and R b are as defined above for formula (4).
  • each of R a and Rj is H, and the remaining occurrences of R a and Rj, are as defined above for formula (4)
  • each of R a and R b is C3 ⁇ 4, and the remaining occurrences of R a and Rj, are as defined above for formula (4).
  • R b , Ra and R b are and the remaining occurrences of R a and Rj, are as defined above for formula (4).
  • each of R a and R b is H, and the remaining occurrences of R a and 3 ⁇ 4 are as defined above for formul a (4),
  • each of R a and is ( I f and the remaining occurrences of R a and R b are as defined above for formula (4).
  • Ra and R ar and the remaining occurrences of R a and b are as defined above for formula (4).
  • R* and R b are and the remaining occurrences of R a and R b are as defined above for formula (4).
  • each of R a and R is H, and the remaining occurrences of R a and 13 ⁇ 4 are as defined above for formula (4)
  • each of R a and R b is CH 3 , and the remaining occurrences of R a and Rj, are as defined above for formula (4).
  • R b , R a and R b are and the remaining occurrences of R a and R b are as defined above for formula (4).
  • each of R a and R b is H, and the remaining occurrences of R a and R b are as defined above for formula (4).
  • each of R a and R b is CH 3 , and the remaining occurrences of R a and R b are as defined above for formula (4).
  • R , R a and R b are and the remaining occurrences of R a and R b are as defined above for formula (4).
  • each of R a and R b is H, and the remaining occurrences of R a and R are as defined above for formula (4),
  • each of R a and R b is CH 3 , and the remaining occurrences of R a and Rj, are as defined above for formula (4).
  • R b , R a and are and the remaining occurrences of R a and R b are as defined above for formula (4).
  • R a and I3 ⁇ 4 are z , and the remaining occurrences of R a and b are as defined above for formula (4).
  • four occurrences of R a and R b are , and the remaining occurrences of R a and R b are as defined above for formula (4).
  • six occurrences of R a and 3 ⁇ 4 are and the remaining occurrences of R a and R b are as defined above for formula (4).
  • eight occurrences of R a and are 3 ⁇ 4 and the remaining occurrences of R a and R 1( are as defined above for formula (4).
  • ten occurrences of R a and R b are 1 .
  • Dl is safranin-O.
  • D2 is safranin-O.
  • Dl and D2 are safranin-O.
  • the pendant phenyl ring of Dl is unsubstituted.
  • the pendant phenyl ring of Dl is substituted with 1-3 (e.g., 1-3, 1 -2, 1, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring.
  • the substituents are selected independently from— H 2 ,— -NHR,— -NR 2 ,— OH,— O " ,— NHCOCH3,— -NHCOR, --OCH3, OR, --C2H5,—R, and ---C 6 H 5 , wherein i s C1 -C6 linear or branched alkyl (e.g., C 1-C6, C1-C5, C 1-C4, C1-C3, C1-C2, C I, C2-C6, C2-C5, C2-C4, C2- C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl).
  • the substituents are selected independently from— N0 2 ,— NR 3 + , halo (e.g., F, Br, CI, I), trihalide (e.g.,— CF 3 , --CCI3,— CBr 3 , --CI3),— CN,— S0 3 H, --CQOH,— COOR,—CHO, and —COR, wherein R is C1-C6 linear or branched alkyl (e.g., C 1-C6, C1-C5, C1-C4, C 1-C3, Cl- C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
  • halo e.g., F, Br, CI, I
  • trihalide e.g.,— CF 3 , --CCI3,— CB
  • the pendant phenyl ring of D2 is unsubstituted.
  • the pendant phenyl ring of 1)2 is substituted with 1-3 (e.g., 1-3, 1 -2, 1, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring.
  • the substituents are selected independently from— NH 2 ,— -NHR,— -NR 2 ,— OH,— O " ,
  • R is C1-C6 linear or branched alkyl (e.g., C1 -C6, C 1 -C5, C1 -C4, C 1 -C3, C1 -C2, C I, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl).
  • C1-C6 linear or branched alkyl e.g., C1 -C6, C 1 -C5, C1 -C4, C 1 -C3, C1 -C2, C I, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl.
  • the substituents are selected independently from— N0 2 ,— NR 3 + , halo (e.g., F, Br, CI, I), trihalide (e.g.,— CF 3 , --CCI 3 , --CBr 3 , --CI 3 ),— CN, SO I i, --COOH, COOR.
  • halo e.g., F, Br, CI, I
  • trihalide e.g.,— CF 3 , --CCI 3 , --CBr 3 , --CI 3
  • CN SO I i, --COOH, COOR.
  • R is C1-C6 linear or branched alkyl (e.g., C 1-C6, C1-C5, C 1-C4, C 1-C3, Cl - C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
  • R is C1-C6 linear or branched alkyl (e.g., C 1-C6, C1-C5, C 1-C4, C 1-C3, Cl - C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
  • Dl and D2 are safranin-0 moieties, as shown in formula (4a):
  • Ri, R 2 , R3, Ri, R3 ⁇ 4, and Rg independently are absent or independently are selected from— -NH 2 ,— NHR,— NR 2 ,— OH,— O " ,— ' NHCOCH 3 ,
  • NHCOR NHCOR,— OCH 3 ,—OR, CM k— R,— C 6 H 5 ,— N0 2 ,— R 3 + , halo (e.g., F, Br, CI, I), triha!ide (e.g. , ⁇ — CC ,— CBr 3 , C h i— CN,— S0 3 H,— COOH,— COOR, ( HO. and—COR), and R is C1 -C6 linear or branched alkyl (e.g.
  • k is 2- 10, each R a and R b is II, and R ⁇ to ⁇ are as described above for formula (4).
  • k is 6 or 8
  • each R a and ⁇ 3 ⁇ 4> is H, and each of j to R ⁇ , independently is absent or is a halo.
  • k is 6 or 8
  • each R a and 3 ⁇ 4 is H, and Ri to Re are all absent.
  • k is 2-10, R a and R b are either H or , and i to c, are as described above for formula (4). In some of these variations, k is 6 or 8, R a and
  • R b are either H or " ⁇ - and each of Ri to R3 ⁇ 4 independently is absent or is a halo.
  • k is 6 or 8
  • R a and Rj are either H or and j to 3 ⁇ 4 are all absent.
  • k is 2- 10, R a and j, are either H or " 3 ⁇ 4 , and i to 3 ⁇ 4 are as described above for formula (4).
  • A is 6 or 8
  • R a and j are either H or " 3 ⁇ 4 , and i to 3 ⁇ 4 are as described above for formula (4).
  • A is 6 or 8
  • R a and j are either H or " 3 ⁇ 4 , and i to 3 ⁇ 4 are as described above for formula (4).
  • A is 6 or 8
  • Rj are either H or ' 3 ⁇ 4 and each of Ri to f , independently is absent or is a halo.
  • k is 6 or 8
  • R a and Rj are either H or ' 3 ⁇ 4 and R s to R 6 are all absent.
  • k is 2- 10, each R a and R 3 ⁇ 4 is H or two of CR a R b are ⁇ and i to e are as described above for formula (4). In some of these variations, k is
  • each R a and R b is H or two of CR a 3 ⁇ 4 are ' L , and each of Ri to 3 ⁇ 4 independently is absent or is a halo.
  • k is 6 or 8
  • each R a and Rj is H or two of CR a R b are
  • n 0-6, and nj is 1-4.
  • Dl and D2 are different cationic dye moieties. In other variations of formula (5), Dl and D2 are the same cationic dye moiety. In some variations of formula (5), Dl and D2 are independently selected from the group consisting of safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue.
  • n is 0-6, 0-5, 0-4, 0- 3, 0-2, 0-1, 1-6, 1-5, 1-4, 1-3, 1-2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, 5-6, 0, I, 2, 3, 4, 5, or 6.
  • n ⁇ is 1-4, 1-3, 1-2, 2-4, 2-3, 3-4, 1 , 2, 3, or 4,
  • Dl is safranin-O.
  • D2 is safranin-O.
  • Dl and D2 are safranin-O.
  • the pendant phenyl ring of Dl is unsubstituted.
  • the pendant phenyl ring of Dl is substituted with 1-3 (e.g., 1-3, 1-2, 1, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring.
  • the pendant phenyl ring of Dl is substituted, the
  • substituents are selected independently from— -NH 2 ,— NHR,— NR 2 ,— OH,— O " ,
  • R is C1-C6 linear or branched alky! (e.g., C1-C6, C 1-C5, C1-C4, C 1-C3, C1-C2, C I , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl).
  • C1-C6 linear or branched alky! e.g., C1-C6, C 1-C5, C1-C4, C 1-C3, C1-C2, C I , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl.
  • the substituents are selected independently from— 0 2 ,— NR 3 ⁇ , halo (e.g., F, Br, CI, I), trihaiide (e.g.,— CF 3 ,— CC1 3 ,— CBr 3 , ( ' !
  • R is C1-C6 linear or branched alkyl (e.g., C 1 -C6, C 1-C5, C1 -C4, C 1-C3, C l- C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched aikyi ).
  • C1-C6 linear or branched alkyl e.g., C 1 -C6, C 1-C5, C1 -C4, C 1-C3, C l- C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched aikyi ).
  • the pendant phenyl ring of 1)2 is unsubstituted.
  • the pendant phenyl ring of D2 is substituted with 1-3 (e.g., 1-3, 1-2, 1, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position 011 the pendant phenyl ring.
  • the substituents are selected independently from— -NH 2 ,— NHR,— NR 2 ,— OH,— O " ,
  • R is C1-C6 linear or branched alkyl (e.g., C1-C6, C 1-C5, C1-C4, C 1-C3, C1-C2, C I , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl).
  • C1-C6 linear or branched alkyl e.g., C1-C6, C 1-C5, C1-C4, C 1-C3, C1-C2, C I , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl.
  • the substituents are selected independently from— -N0 2 ,— -NR 3 + , halo (e.g., F, Br, CI, I), trihaiide (e.g.,— CF 3 ,— CCI 3 ,— CBr 3 ,— CI 3 ),— CN,— SO 3 H, -—COOH, -—COOR,— CHO, and — COR, wherein R is C1.-C6 linear or branched al kyl (e.g., C 1 -C6, C1-C5, C 1 -C4, C 1 -C3, C l- C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
  • halo e.g., F, Br, CI, I
  • each of Dl and D2 is a cationic dye moiety
  • fir is 0-5, and n 2 is 1-5.
  • Dl and D2 are different cationic dye moieties. In other variations of formula (6), Dl and D2 are the same cationic dye moiety. In some variations of formula (6), Dl and D2 are independently selected from the group consisting of safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue. [137] In some variations of formula (6) described in the paragraphs above, n ⁇ is 0-5, 0-4, 0-3,
  • n 2 is 1 -5, 1-4, 1-3,
  • Dl is safranin-O.
  • D2 is safranin-O.
  • Dl and D2 are safranin-O.
  • the pendant phenyl ring of Dl is unsubstituted.
  • the pendant phenyl ring of Dl is substituted with 1-3 (e.g., 1 -3, 1-2, 1 , 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring.
  • the substituents are selected independently from— -NH 2 ,— NHR,— NR 2 ,— OH,— O " ,
  • ICOCH3, XI li OR. (X I k—OR,— C2H5,— R, and G,! k wherein R is C1-C6 linear or branched alkyl (e.g., C1-C6, C1-C5, C1-C4, C 1-C3, C1-C2, CI , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl).
  • R is C1-C6 linear or branched alkyl (e.g., C1-C6, C1-C5, C1-C4, C 1-C3, C1-C2, CI , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6,
  • the substituents are selected independently from— O?,— NR 3 ⁇ , halo (e.g., F, Br, CI, I), trihaiide (e.g.,— CF 3 , --CCI3, ---CBr 3 , --CI3),— CN, SO;!
  • halo e.g., F, Br, CI, I
  • trihaiide e.g.,— CF 3 , --CCI3, ---CBr 3 , --CI3
  • R is C1-C6 linear or branched alkyl (e.g., C 1-C6, C1-C5, C1-C4, C 1-C3, Cl- C2, CI , C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
  • C1-C6 linear or branched alkyl e.g., C 1-C6, C1-C5, C1-C4, C 1-C3, Cl- C2, CI , C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl.
  • the pendant phenyl ring of D2 is unsubstituted.
  • the pendant phenyl ring of D2 is substituted with 1-3 (e.g., 1-3, 1-2, 1, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring.
  • the substituents are selected independently from— -NH 2 ,— NHR,— NR 2 ,— OH,— O " ,
  • R is C1-C6 linear or branched alkyl (e.g., C1-C6, C1-C5, C1-C4, C1-C3, C1-C2, CI , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl ).
  • C1-C6 linear or branched alkyl e.g., C1-C6, C1-C5, C1-C4, C1-C3, C1-C2, CI , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl ).
  • the substituents are selected independently from— -N0 2 ,— -N 3 + , halo (e.g., F, Br, CI, I), trihalide (e.g.,— CF 3 ,— CC1 3 ,— CBr 3 ,— CI 3 ),— CN,— SO 3 H, ⁇ — COOH,— COOR,— CHO, and — COR, wherein R is C1-C6 linear or branched alkyl (e.g., C1-C6, C1-C5, C1-C4, C1-C3, Cl- C2, CI, ( ' 2 ⁇ ( ⁇ (>, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-
  • halo e.g., F, Br, CI, I
  • trihalide e.g.,— CF 3 ,— CC
  • Dl and D2 are different cationic dye moieties. In other variations of formula (7), Dl and D2 are the same cationic dye moiety. In some variations of formula (7), Dl and D2 are independently selected from the group consisting of safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue.
  • tj is 0-5, 0-4, 0-3,
  • n 2 is 1-5, 1-4, 1-3,
  • Dl is safranin-O.
  • D2 is safranin-O.
  • Dl and D2 are safranin-O.
  • the pendant phenyl ring of Dl is un substituted. In some variations of formula (7) described in the paragraph above, the pendant phenyl ring of Dl is substituted with 1-3 (e.g., 1-3, 1-2, I, 2, or 3) electron-donating or electro -with drawing groups, which may be at any available position on the pendant phenyl ring.
  • 1-3 e.g., 1-3, 1-2, I, 2, or 3
  • the substituents are selected independently from— NH 2 ,— -NHR,— NR 2 ,— OH,— O " , --NHCOCH 3 ,— -NHCOR, --OCH 3 ,—OR, --C2H5, R, and— C 6 H 5 , wherein R is C1-C6 linear or branched alkyl (e.g., C1-C6, C 1-C5, C1-C4, C1-C3, C1-C2, CI, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl).
  • R is C1-C6 linear or branched alkyl (e.g., C1-C6, C 1-C5, C1-C4, C1-C3, C1-C2, CI, C2-C6, C2-C5, C2- C4, C2-C
  • the substituents are selected independently from— N0 2 ,— NR 3 + , halo (e.g., F, Br, CI, I), trihalide (e.g.,— CF 3 , CCk— CBr 3 ,—CI3),— CN,— S0 3 H, COOH,— COOR,—CHO, and — COR, wherein R is C1-C6 linear or branched alkyl (e.g., C1-C6, C1-C5, C1-C4, C 1-C3, Cl- C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
  • halo e.g., F, Br, CI, I
  • trihalide e.g.,— CF 3 , CCk— CBr 3
  • the pendant phenyl ring of D2 is unsubstituted.
  • the pendant phenyl ring of 1)2 is substituted with 1-3 (e.g., 1-3, 1 -2, 1, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring.
  • the substituents are selected independently from— NH 2 ,— -NHR,— -NR 2 ,— OH,— O " ,
  • R is C1-C6 linear or branched alkyl (e.g., C1 -C6, C 1 -C5, C1 -C4, C1 -C3, C1-C2, CI, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl).
  • C1-C6 linear or branched alkyl e.g., C1 -C6, C 1 -C5, C1 -C4, C1 -C3, C1-C2, CI, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl.
  • the substituents are selected independently from— N0 2 ,— NR 3 + , halo (e.g., F, Br, CI, I), trihalide (e.g.,— CF 3 , --CCI 3 , --CBr 3 , --CI 3 ),— CN, SO I i, COOH, COOR.
  • halo e.g., F, Br, CI, I
  • trihalide e.g.,— CF 3 , --CCI 3 , --CBr 3 , --CI 3
  • SO I i e.g., COOH, COOR.
  • R is C1-C6 linear or branched alkyl (e.g., C1-C6, C1-C5, C1-C4, C1-C3, Cl - C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
  • R is C1-C6 linear or branched alkyl (e.g., C1-C6, C1-C5, C1-C4, C1-C3, Cl - C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
  • each of Dl and D2 is a cationic dye moiety, n ⁇ is 0-5, and n 2 is 1-5.
  • Dl and D2 are different cationic dye moieties.
  • Dl and D2 are the same cationic dye moiety.
  • Dl and D2 are independently selected from the group consisting of safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue.
  • n ⁇ is 0-5, 0-4, 0-3,
  • n 2 is 1 -5, 1-4, 1-3,
  • Dl is safranin-O.
  • D2 is safranin-O.
  • Dl and D2 are safranin-O.
  • the pendant phenyl ring of Dl is unsubstituted.
  • the pendant phenyl ring of Dl is substituted with 1-3 ⁇ e.g., 1-3, 1-2, 1, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring.
  • the substituents are selected independently from— M k— NHR,— NR 2 ,— OH,— O " ,
  • R is C1-C6 linear or branched alky! ⁇ e.g., C1-C6, C1-C5, C1-C4, C1-C3, C1-C2, CI , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl).
  • the substituents are selected independently from— -NO 2 ,— - R 3 + , halo ⁇ e.g., F, Br, CI, I), trihalide ⁇ e.g.,— CF 3 ,— CCI3,— CBr 3 , ( O..— CN, SO: I f .— COOH,— COOR,— CIIO, and — COR, wherein R is C1-C6 linear or branched alkyl ⁇ e.g., C1-C6, C1-C5, C1-C4, C 1-C3, Cl- C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
  • the pendant phenyl ring of 1)2 is unsubstituted.
  • the pendant phenyl ring of D2 is substituted with 1-3 ⁇ e.g., 1-3, 1-2, I, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring.
  • the substituents are selected independently from— -NH 2 ,— NHR,— NR 2 ,— OH,— O " , — NHCOCH 3 ,— -NHCOR, --OCH3,—OR, --C2H5, R, and --C 6 H 5 , wherein R is C1-C6 linear or branched aikyi (e.g., C1-C6, C 1-C5, C1-C4, C 1-C3, C 1-C2, C I, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched aikyi).
  • R is C1-C6 linear or branched aikyi (e.g., C1-C6, C 1-C5, C1-C4, C 1-C3, C 1-C2, C I, C2-C6, C2-C5, C2- C4, C2-
  • the substituents are selected independently from— N0 2 ,— R 3 + , halo (e.g., F, Br, CI, I), trihalide (e.g., ---CF 3 , CCk --CBr 3 ,—CI3),— CN, - -SO3H,—COOH,— COOR,—CHO, and — COR, wherein R is C1-C6 linear or branched aikyi (e.g., C 1-C6, C1-C5, C1-C4, C 1-C3, Cl- C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched aikyi).
  • halo e.g., F, Br, CI, I
  • trihalide e.g., ---CF 3 , CCk --
  • Dl and D2 are different cationic dye moieties. In other variations of formula (9), Dl and D2 are the same cationic dye moiety. In some variations of formula (9), Dl and D2 are independently selected from the group consi sting of safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue.
  • rij is 1-5, 1 -4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, I , 2, 3, 4, or 5.
  • « 2 is 1-5, 1 -4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, I , 2, 3, 4, or 5.
  • Dl is safranin-O.
  • D2 is safranin-O.
  • Dl and D2 are safranin-O.
  • the pendant phenyl ring of Dl is unsubstituted.
  • the pendant phenyl ring of Dl is substituted with 1-3 (e.g., 1-3, 1 -2, 1, 2, or 3) electron-donating or electro -with drawing groups, which may be at any available position on the pendant phenyl ring.
  • the substituents are selected independently from— NH 2 ,— NHR,— NR 2 ,— OH,— O " ,
  • R is C1-C6 linear or branched alkyl (e.g., C 1 -C6, C 1 -C5, C 1-C4, C 1 -C3, C 1-C2, CI, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl).
  • C1-C6 linear or branched alkyl e.g., C 1 -C6, C 1 -C5, C 1-C4, C 1 -C3, C 1-C2, CI, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl.
  • the substituents are selected independently from— N0 2 ,— ' NR 3 T , halo (e.g., F, Br, CI, I), trihalide (e.g.
  • R is C1 -C6 linear or branched alkyl (e.g., C 1-C6, C1 -C5, C1-C4, C 1-C3, Cl - C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
  • C1 -C6 linear or branched alkyl e.g., C 1-C6, C1 -C5, C1-C4, C 1-C3, Cl - C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl.
  • the pendant phenyl ring of D2 is unsubstituted.
  • the pendant phenyl ring of D2 is substituted with 1-3 (e.g., 1 -3, 1-2, 1 , 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring.
  • the substituents are selected independently from— NH?,— NHR,— NR 2 ,— OH,— O " ,
  • R is C1 -C6 linear or branched alkyl (e.g., C 1-C6, C 1-C5, C 1-C4, C 1-C3, C 1-C2, CI, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl).
  • C1 -C6 linear or branched alkyl e.g., C 1-C6, C 1-C5, C 1-C4, C 1-C3, C 1-C2, CI, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl.
  • the substituents are selected independently from— 0 2 ,— R 3 1 , halo (e.g., F, Br, CI, I), trihalide (e.g.
  • R is C 1-C6 linear or branched alkyl (e.g., C 1-C6, C 1-C5, C1-C4, C 1-C3, C l - C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
  • R is C 1-C6 linear or branched alkyl (e.g., C 1-C6, C 1-C5, C1-C4, C 1-C3, C l - C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
  • Some cationic dye mul timers fall within formula (10):
  • Dl and D2 are different cationic dye moieties. In some variations of formula (10), Dl and D2 are the same cationic dye moiety. In some variations of formula (10), Dl and D2 independently are selected from the group consisting of safranin-O, toiuidine blue, azure A, azure B, azure C, acridine orange, acrifiavine, and methylene blue.
  • n is 1 -6, 1-5, 1 -4, 1-3, 1-2, 2-6, 2-5, 12-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, 5-6, 1, 2, 3, 4, 5, or 6,
  • Dl is safranin-O.
  • D2 is safranin-O.
  • Dl and D2 are safranin-O.
  • the pendant phenyl ring of Dl is unsubstituted.
  • the pendant phenyl ring of Dl is substituted with 1-3 (e.g., 1-3, 1-2, 1, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring.
  • the pendant phenyl ring of Dl is substituted, the
  • substituents are selected independently from— NH 2 ,— NHR,— NR 2 ,— OH,— O " ,
  • R is C1-C6 linear or branched alky! (e.g., C 1-C6, C 1-C5, C1-C4, C 1-C3, C1-C2, C I , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched aikyi).
  • C1-C6 linear or branched alky! e.g., C 1-C6, C 1-C5, C1-C4, C 1-C3, C1-C2, C I , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched aikyi).
  • the substituents are selected independently from— -N0 2 ,— -N 3 + , halo (e.g., F, Br, CI, I), trihalide (e.g.,— CF 3 ,— CCI3,— CBr 3 ,— CI 3 ),— CN,— SO3H, ⁇ — COOH,— COOR,— CHO, and — COR, wherein R is C1-C6 linear or branched al ky] (e.g., C 1 -C6, C1-C5, C 1 -C4, C 1 -C3, C l- C2, CI , C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-
  • halo e.g., F, Br, CI, I
  • trihalide e.g.,— CF 3 ,— CCI3,— CB
  • the pendant phenyl ring of D2 is unsubstituted.
  • the pendant phenyl ring of D2 is substituted with 1-3 (e.g., 1 -3, 1-2, 1 , 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring.
  • the pendant phenyl ring of D2 is substituted, the
  • substituents are selected independently from— -NH 2 ,— NHR,— NR 2 ,— OH,— O " ,
  • R is C 1-C6 linear or branched alkyl (e.g., C 1-C6, C 1-C5, C1-C4, C 1-C3, C1-C2, CI , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl ).
  • C 1-C6 linear or branched alkyl e.g., C 1-C6, C 1-C5, C1-C4, C 1-C3, C1-C2, CI , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl ).
  • the substituents are selected independently from— -NO 2 ,— -NR 3 + , halo (e.g., F, Br, CI, I), trihalide (e.g.
  • R is C1-C6 linear or branched alkyl (e.g., C 1 -C6, C 1-C5, C1 -C4, C 1-C3, C l- C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
  • C1-C6 linear or branched alkyl e.g., C 1 -C6, C 1-C5, C1 -C4, C 1-C3, C l- C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
  • Dl and D2 are safranin-0 moieties, as shown in formula (10a):
  • n 1 -6, Rj, R 2 , R3, R4, R5, and R independently are absent or independently are selected from ⁇ i k—NHR,— NR 2 ,—OH,— O " ,— NHCOCH 3 ,— NHCOR,— OCH 3 ,—OR,
  • R is C 1-C6 linear or branched alkyl (e.g., C1 -C6, C 1 -C5, C1 -C4, C 1 -C3, C1 -C2, C I, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl).
  • halo e.g., F, Br, CI, I
  • trihalide e.g., --CF 3 , --CCI 3 , — CBr 3 ,— CI 3
  • R is C 1-C6 linear or branched alkyl (e.g., C1 -C6, C 1 -C5, C1 -C4, C 1 -C3, C1 -C2, C I, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C
  • n is 1-6, 1-5, 1-4, 1-3, 1-2, 2-6, 2-5, 2-4, 2-3, 3-6, 3- 5, 3-4, 4-6, 4-5, 5-6, 1, 2, 3, 4, 5, or 6.
  • I 2 independently are 1-4; n is 1-4; ring A is aryl, heteroaryl, cycloalkyl, or heterocyclyl; for each independent instance of a i and J3 ⁇ 4 ( i , R a i and 3 ⁇ 4i (1) independently are H or CH 3 , or (2) R al and i b i are or or (3) two of CRaiR b i are ; and, for each independ instance of R3 ⁇ 42 and Rb 2 , a2 and R 2 (1 ) independently are H or CH 3 , or (2) R a2 and R3 ⁇ 4 2 are or or (3) two of C a 2R!2 are
  • Dl and D2 are different catiomc dye moieties. In other variations of formula (1 1), Dl and D2 are the same cationic dye moiety. In some variations of formula (1 1 ), Dl and D2 are independently selected from the group consisting of safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue.
  • h is 1-4, 1-3, 1-2, 2-4, 2-3, 3-4, l , 2, 3, or 4.
  • each of R a i and R b i is H and ⁇ and Rj, 2 are O
  • Rb2 are in some variations of formula (1 1 ) described in the paragraphs above in which
  • R al and Rbi are '3 ⁇ 4
  • R a2 and b2 are ⁇
  • each of Rai,Rbj, R a2 , and Rb 2 is H and each of Ra3 and R ⁇ i s CH 3 .
  • each of Rai,Rbi, a 2, and 3 ⁇ 4 2 is CH 3 and each of Ra3 and Rj, 3 is H.
  • each of R a i,Rbi, a2, and Rb 2 is H and .
  • each of R a i,R b i, R A 2, and R b2 is CH 3 and A 3 and Rb3 are " .
  • R a i is H and each of R a2 , Rbi , and R b2 is CH 3 , and R a3 and R b3 are " ⁇ - .
  • each of R a i,R w , R a2 , and 3 ⁇ 4>2, is H and Ra3 and 13 ⁇ 43 are "3 ⁇ 4 ⁇
  • each of R a i,3 ⁇ 4i, Ra2, and 3 ⁇ 42, is CH 3 and a 3
  • Rj, 3 are ' ⁇ - In some variations of formula (1 1 ) described in the paragraphs above in which
  • R b i and 3 ⁇ 4 2 is CH 3
  • R a s and R3 ⁇ 43 are "3 ⁇ 4
  • R a i and R b i are anc f each of R a3 an( j R b3 i s en .
  • R i are R a2 and 3 ⁇ 42 are , and each of R ⁇ and R b3 is H.
  • formula (1 1 ) descri bed in the paragraphs above in which i s 3, R a i and R b i are ' 3 ⁇ 4 ⁇ R a2 and O
  • R a i and R 3 ⁇ 4 i are " 3 ⁇ 4 R a2 and Rj, 2 are ' 3 ⁇ 4 ⁇ and each of A3 and ⁇ is H.
  • R a i and RM are
  • R a3 i s H R b3 is CH 3 .
  • Rj,i are R a2 and R b2 are * 3 ⁇ 4 ⁇ and each of R a s and b3is H.
  • R AI and R t> i are , R A2 and 3 ⁇ 4 2 are '3 ⁇ 4 ⁇ A is H, and b33 ⁇ 4 s CH 3 .
  • a i and Rbi are and each of a s and bsis H.
  • formula (11) described in the paragraphs above in which l ⁇ is 3, a j and R ⁇ are O O
  • each of Rai,Rt>i, 3 ⁇ 42, 2, a3, 3, A , and 3 ⁇ 44 is CH 3 .
  • each of Rai, Ra2, i>2, a3, a d R ⁇ is H and each of R A4 and ⁇ is CH 3 .
  • each of R a i, 3 ⁇ 4 i, R a2 , and Rj, 2 is H and each of Ra3, Rj> 3 .
  • R A 4 , and R ⁇ is CH 3 .
  • each of R a ⁇ ,R a2 , and R a3 is II and each of RM, (, 2 , and j, 3 is CH 3 .
  • R ai is H
  • *i is CH 3
  • each of Ra2, 3 ⁇ 42, a3, and j,3 is CH 3 .
  • R ai is H
  • R3 ⁇ 4i is CH 3
  • each of R ⁇ , M, A 3 , and R 3 is H.
  • each of Rai and R a2 is H, each of M and j, 2 is CH 3 , and each of R a3 and !1 ⁇ 2 is H.
  • each of Rai and R a2 is H, each of RM and Rb2 is ( ⁇ f and each of R a3 and 3 ⁇ 4 3 is CH 3 .
  • R ai is 4, R ai
  • Ra2 and R b2 are H, R a3 and R b3 are CH 3 , and Ra 4 and R 4 are ' 3 ⁇ 4 .
  • R ai and 3 ⁇ 4 ⁇ are H, R ⁇ and 3 ⁇ 4 2 are CII 3 , 3 ⁇ 4 and 3 ⁇ 4 3 are CH 3 , and R A4 and 3 ⁇ 4 4 are ' 3 ⁇ 4 ,
  • R a i and b i are CH 3
  • R a2 and R b2 are CH 3 ,
  • R a3 and B3 are CH 3
  • R a4 and R 3 ⁇ 44 are " 3 ⁇ 4 ⁇ .
  • R a2 and R 2 are CH 3 , A3 and * »3 are , In some variations of formula (11) described in the paragraphs above in which i ⁇ is 4, R a! and & j are CH 3 , R a2 and
  • Rb2 are CH 3
  • R ⁇ and Rb3 are " ⁇ -
  • R a4 and R 4 are " 3 ⁇ 4 .
  • R a3 and 3 ⁇ 4> 3 are L and R a4 and R 3 ⁇ 44 are ' 3 ⁇ 4 .
  • R b2 is CH 3 , A3
  • R a4 a d R3 ⁇ 4 4 are ⁇ .
  • Ra2 and R b2 are H, R a3 and (,3 are CH 3 , and A 4 and K M are .
  • a i and R i are H, ⁇ and 2
  • R a3 and R b5 are CH 3 , and R a4 and M are " ⁇ - .
  • R b i are H
  • R ⁇ and ⁇ 3 ⁇ 4> 2 are H
  • R a3 and 3 are ' 3 ⁇ 4 ⁇ ⁇
  • R a and R ⁇ v % are v.
  • R b2 are CH 3
  • R a3 and s are In some variations of formula (11) described in the paragraphs above in which is 4, a i and b i are CH 3 , R a2 and
  • a A CH 3 , R a3 and 3 ⁇ 4>3 are and R a4 and 4 are
  • R a i is H
  • R 3 ⁇ 4 i is CH 3
  • R ⁇ is H
  • 3 ⁇ 42 is CH 3
  • a 3 and b a are [193]
  • Rb2 are CH 3
  • R a3 and R b3 are CH 3
  • R a4 and M are ' 3 ⁇ 4 A ⁇ .
  • R ai and ⁇ 3 ⁇ 4 ⁇ are ' 3 ⁇ 4 ⁇ *
  • R a i and R b i are ' 3 ⁇ 4
  • R a2 and Rj, 2 are ' 3 ⁇ 4
  • R a and R 3 ⁇ 4 are H
  • R a4 and R3 ⁇ 44 are .
  • Rj,i are " ⁇ R a2 and 2 are r ⁇ R a 3 and j,3 are H, and R a4 and Ri>.i are f ⁇
  • _ is 4
  • R a i and M are in some variations of formula ( 1 1) described in the paragraphs above in which l ⁇ is 4, R a! and & j are in some variations of formula (1 1) described in the paragraphs above in which h is 4, R ai and R3 ⁇ 4i are 3 ⁇ 4 ' 3 ⁇ 4 ⁇ / . [198] In some variations of formula (1 1 ) described in the paragraphs above in which h is 4, R ai
  • a 2 and R b2 are ⁇ f ⁇ R a3 and R b3 are H, and R a and R b are ' 3 ⁇ 4 ⁇ ⁇ .
  • R al and R bi are H, R ⁇ and R b2 are " 3 ⁇ 4 and R a3 and R b3 and R a4 and R b together are ⁇ r .
  • R a2 and R b2 are CH 3
  • R a3 and R 3 and R a4 and R b4 together are ' * ⁇ .
  • a j is H
  • i is
  • R a i and R a i are "3 ⁇ 4 R A2 and R b2 are '3 ⁇ 4 and R ⁇ and ? and R A4 and RM together are 3 ⁇ 4 x .
  • R a i and R a i are "3 ⁇ 4 R A2 and R b2 are '3 ⁇ 4 and R ⁇ and ? and R A4 and RM together are 3 ⁇ 4 x .
  • R f ci are R ⁇ and j >2 are " 3 ⁇ 4 ⁇ and R a3 and M and R a4 and M together are " ⁇ - 1 .
  • v ' ⁇ A- R a2 and Rb 2 are 3 ⁇ 4 '3 ⁇ 4 A ⁇ / and A 3 and j,3 and R a 4 and j )4 together are 3 ⁇ 4 - ⁇ Y 3 ⁇ 4 .
  • each of Rai and R a2 is H and each of R b i and Rb2 is CH 3 .
  • each of R a i and RM is H and and R 1(2 are ' 3 ⁇ 4
  • each of Rai and 3 ⁇ 4 i is H and R a2 and R ⁇ i are O
  • R a2 and Rj >2 together are .
  • R ai and RM are " 3 ⁇ 4 Ra2 and t, 2 are ' 3 ⁇ 4 .
  • R ai and 1( i are ⁇ ⁇ and j, 2 are .
  • each of R a j,Rbi, a z, and R b2 is H and each of Ra3 and is CH 3 .
  • each of Raj,Rbi, R a z, and 3 ⁇ 4 2 is CH 3 and each of R ⁇ and .-? is H.
  • R a i is H and each of Ra2, Ra3, 3 ⁇ 4 ⁇ , 3 ⁇ 42, and R b 3 is CH 3 .
  • each of R aJ and R a2 is H and each of R a3j 3 ⁇ 4 )5 3 ⁇ 4 2 , and 3 is CH 3 .
  • each of a i, R a2 , and A 3 is H and each of Rbi , 2, and bs is CH 3 .
  • each of R a i,Rbi, a2, and R b2 is H and a3 and R 3 are " ⁇ ⁇ .
  • each of R a i,Rbi, R a2 , and R b2 is CH 3 and R a3 and Rb3 are " ⁇ - ⁇ .
  • R ai is H and each of R a2 , 3 ⁇ 4 ⁇ , and R b ? is CH 3
  • R A3 and 3 ⁇ 4 3 are .
  • each of Rai and a 2 is H and each of M and R 3 ⁇ 42 is CH 3 , and R a3 and . h3 are .
  • each of R a ⁇ ,Rbi, R a 2, and 2 is H and ⁇ and 3 ⁇ 43 are ⁇ .
  • each of 3 ⁇ 4 ⁇ and 3 ⁇ 4 2 is CH 3 , and A 3 and 3 ⁇ 43 are 3 ⁇ 4 '3 ⁇ 4 A ⁇ ⁇ ⁇
  • R a2 and R b2 are ' 3 ⁇ 4 ⁇
  • each of and ⁇ 3 is H.
  • R a2 and j, 2 are , and each of R a3 and R3 ⁇ 43 is CH 3 .
  • R a i and R b i are " x R a2 and Rbi are
  • Rb2 are ⁇ and each of a 3 and j, 3 is C3 ⁇ 4.
  • Rb2 are the parag raphs above in which l is 3, R ai and R bi
  • Rb3 is CH 3 .
  • Ra3 is H
  • R b3 is CH 3
  • each of R a i,Rt > i, a2, R3 ⁇ 42, a3, Rb3, a4, and ⁇ is CH 3 .
  • each of R a i, M, 2, Rb2, 3, and 3 ⁇ 4 3 is H and each of R 34 and j, 4 is CH 3 .
  • each of R a j, RM, R a 2, and Rj>2 is H and each of Ra3, 3 ⁇ 4> 3 , R a 4, and R ⁇ is CH 3 .
  • each of R a i, RM, a 2, Rb2, 3 ⁇ 43, and ⁇ is CH 3 and each of R 3 ⁇ 4 4 and Rb4 is H.
  • each of R a i and R ⁇ is H, each of RM and R
  • each of R a i and R ⁇ is H, each of R and R 2 is CH 3 , and each of R a3 and 3 ⁇ 4 3 is CH 3 .
  • Ra2 and ⁇ are H, R A3 and ⁇ are CH 3 , and R A4 and R3 ⁇ 4 4 are ' 3 ⁇ 4 .
  • R AI and RM are H, ⁇ and R t , 2
  • Ra3 and j, 3 are CH 3
  • R a4 and R 3 ⁇ 44 are w " 3 ⁇ 4 .
  • Rj,2 are CH 3
  • R a3 and 3 ⁇ 43 are
  • R A4 and 3 ⁇ 4 4 are " 3 ⁇ 4 .
  • R ai is H
  • 3 ⁇ 4j is CH 3
  • R a2 and Rj, 2 are
  • R a3 and R 3 ⁇ 4 , 3 are 3 ⁇ 4 - " , and R a4 and 3 ⁇ 4 are .
  • R AJ is H
  • R 3 ⁇ 4 i is CH 3
  • R a2 is H
  • j 2 is CH 3
  • R a2 and t, 2 are II, R a3 and t, 3 are CH 3 , and R a4 and R 3 ⁇ 44 are '3 ⁇ 4 ⁇ *" .
  • Ra3 and (,3 are CH 3 , and R a4 and R3 ⁇ 4, 4 are X ⁇ .
  • R ai In some variations of formula (1 1) described in the paragraphs above in which l 2 is 4, R ai
  • R a2 and j> 2 are H
  • R a3 and R3 ⁇ 43 are 3 ⁇ 4 ' 3 ⁇ 4A ⁇
  • R a 4 and 3 ⁇ 44 are v.
  • R a 2 and j, 2 are CH 3
  • R a3 and 3 ⁇ 4 3 are " ⁇ -
  • R a4 and R ⁇ are " ⁇ -
  • formula (1 1) described in the paragraphs above in which l 2 is 4, R a! and R ⁇ are CH 3 , R a2 and
  • Rb2 are CH 3 , R A 3 and Rj,3 are ⁇ and R a4 and are ' 3 ⁇ 4 ⁇ .
  • R ai is H
  • R M is CH 3
  • R a2 and j> 2 are CH 3
  • Ra3 and ,3 are .
  • R a2 is H
  • 3 ⁇ 4 2 is C3 ⁇ 4, R A 3 and Rj,3 are
  • R f ci are H
  • R a2 and i, 2 are '3 ⁇ 4
  • a 3 and R3 ⁇ 4,3 are "3 ⁇ 4 and A 4 and j,4 are '3 ⁇ 4 ⁇ .
  • R b i are ' 3 ⁇ 4 ⁇ ⁇ * ⁇ In some variations of formula (1 1) described in the paragraphs above in which l 2 is 4, R a ⁇ and R b i
  • R a2 and R b2 are ' 3 ⁇ 4 ⁇ ⁇ and R b3 are CH 3
  • R a4 and R b4 are ' L .
  • I? i s 4 a i and R b i are .
  • R al and R M are , Ra2 and R b2 are , R a3 and R 3 are H, and R a4 and R b4 are "3 ⁇ 4 .
  • R a2 and R b2 are In some vari ations of formula (1 1) described in the paragraphs above in which h is 4, R ai and R b i are In some variations of formula (1 1 ) described in the paragraphs above in which 1 2 is 4, R a! and b j are In some variations of formula (1 1 ) described in the paragraphs above in which l 2 i s 4, a i and R i are
  • Ra2 and Rj,2 are ' « ⁇ 3 3 and R3 ⁇ 4s are CH 3 , and R a4 and R b4 are 5 ,
  • R a! and R i are .
  • R ai and b i are .
  • R a2 and R b2 are CH 3
  • R a3 and R 3 and R a4 and R B together are 3 ⁇ 4
  • R a! is H
  • R bi is
  • n is 1-4, 1-3, 1-2, 2-4, 2-3, 3-4, 1 , 2, 3, or 4,
  • ring A is substituted with halo.
  • the halo is F, Br, I, or Ci.
  • ring A is substituted with C1-C6 linear or branched alkyl (e.g., C 1 -C6, C 1 -C5, C1-C4, C1-C3, C 1-C2, C I , C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl).
  • C1-C6 linear or branched alkyl e.g., C 1 -C6, C 1 -C5, C1-C4, C1-C3, C 1-C2, C I , C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl.
  • Dl is safranin-O.
  • D2 is safranin-O.
  • Dl and D2 are safranin-O.
  • the pendant phenyl ring of 1)1 is unsubstituted.
  • the pendant phenyl ring of Dl is substituted with 1-3 (e.g., 1-3, 1-2, I, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring.
  • the pendant phenyl ring of Dl is substituted, the
  • substituents are selected independently from— NH 2 ,— NHR,— NR 2 ,— OH,— O " ,
  • R is C1-C6 linear or branched alkyl (e.g., C1-C6, C 1-C5, C1-C4, C 1-C3, C1-C2, C I , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl).
  • C1-C6 linear or branched alkyl e.g., C1-C6, C 1-C5, C1-C4, C 1-C3, C1-C2, C I , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl.
  • the substituents are selected independently from— N0 2 ,— NR 3 T , halo (e.g., F, Br, CI, I), trihalide (e.g., --CF 3 , --CCI3, ---CBr 3 , CI : ⁇ ,— CN, --SO3H, --COOH, --COOR, --CHO, and — COR, wherein R is C1-C6 linear or branched alkyl (e.g., C1-C6, C1-C5, C1-C4, C 1-C3, Cl - C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
  • halo e.g., F, Br, CI, I
  • trihalide e.g., --CF 3 , --CCI3,
  • the pendant phenyl ring of D2 is unsubstituted.
  • the pendant phenyl ring of D2 is substituted with 1-3 (e.g., 1 -3, 1-2, 1 , 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring.
  • the substituents are selected independently from— -NH 2 ,— NHR,— R 2 ,— OH,— O " ,
  • R is C1-C6 linear or branched alkyl (e.g., C1-C6, C1-C5, C1-C4, C 1-C3, C1-C2, CI , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl ).
  • C1-C6 linear or branched alkyl e.g., C1-C6, C1-C5, C1-C4, C 1-C3, C1-C2, CI , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl ).
  • the substituents are selected independently from— O?,— NR 3 ⁇ , halo (e.g., F, Br, CI, I), trihalide (e.g., --CF3, --CCI3, ---CBr 3 , --CI3),— CN, --SO3H, COO! !
  • R is C1-C6 linear or branched alkyl (e.g., C 1-C6, C1-C5, C1-C4, C 1-C3, Cl- C2, CI , C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
  • R is C1-C6 linear or branched alkyl (e.g., C 1-C6, C1-C5, C1-C4, C 1-C3, Cl- C2, CI , C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
  • Dl and D2 are safranin-0 moieties, as shown in formula (11a):
  • Rbi 3 ⁇ 4 2, and Rj,2 are as described in the paragraphs above, Ri, R2, R3, R4, Rs, and 3 ⁇ 4
  • R a i and Rbi independently are H or CH 3 , or (2) R ai and R3 ⁇ 4i are or (3) two of CRaiRbi are
  • Ra2 an R3 ⁇ 42 (1 ) independently are H or
  • a2 and Rt> 2 are " ⁇ - or ? or (3) two of CR a2 Rb2 are v for each independent instance of R cl and and R dl (1) independently are H or CH 3 , or (2) and
  • Rdi are ' 3 ⁇ 4 or ⁇ nr ⁇ wn of ⁇ subject, ⁇ 3 ⁇ 4. « are. - for each independent instance of c 2
  • Rc2 and (1) independently are H or CH 3 , or (2) c 2 and 3 ⁇ 4 2 are W orA or
  • the catiomc dye moiety is selected from the group consisting of safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue.
  • Dl and D2 are different cationic dye moieties.
  • Dl and D2 are the same cationic dye moiety.
  • o 2 is 1-4, 1-3, 1 -2, 2-4, 2-3, 3-4, 1 , 2, 3, or 4,
  • each of R a i and Rm is H and R a2 and R b2 are " 3 ⁇ 4 .
  • each of Rai and R3 ⁇ 4i is H and ⁇ and i, 2 are O
  • each of R a i and w is CH 3 and R a2 and R b2 are .
  • each of R ai and R M is CH 3 and ⁇ and Rj, 2 O
  • R a2 and t, 2 together are ⁇
  • R aS and R 3 ⁇ 4 i are " ⁇ - ⁇ and R 3 ⁇ 42 are " ⁇ - ,
  • R a! and R ⁇ are ' 3 ⁇ 4 a a and b 2 described in the paragraphs above in which U is 2
  • R al and R & j are R a2 and R b2 are
  • each of R a i,Rbi, R a2 , and R b2 is H and each of R a3 and R b3 is CH 3 .
  • each of R a i,Rbi, R a2 , and R b2 is CH 3 and each of a s and b .? is H.
  • R a i is H and each of R a2 , Ra3 ; Rbi, b2, and b3 is CH 3 .
  • each of R ai and R a2 is H and each of R a3; R M , R b2 , and R b j is CH 3 .
  • each of R a i,3 ⁇ 4i, Ra2, and J3 ⁇ 4, 2 is H and a3 and 3 ⁇ 4 3 are w " 3 ⁇ 4 .
  • each of Rai,R b i, a2, and Rj>2 is CH 3 and R a3 and Rb3 are " ⁇ - .
  • R ai is H and each of R a2 , R
  • each of R a i and R a2 is H and each of R b i and 3 ⁇ 4 2 is CH 3 , and a 3 and Rb3 are
  • each of R a i,R b i, R a2 , and j,?, is H and R ⁇ and b3 are "3 ⁇ 4 .
  • each of R a i,R b i, Ra2, and R M is CH 3 and R a3
  • R a2 and R 2 are 3 ⁇ 4 '3 ⁇ 4A ⁇ and each of R 3 ⁇ 4 3 and Rb3 is H.
  • b 2 are 3 ⁇ 4 '3 ⁇ 4 A and each of A3 and b3 is CH 3 .
  • Ra3 is H
  • is CH 3 .
  • R a3 and M and a2 and R 3 ⁇ 4 , 2 together are and R a3 and i, 3 are
  • each of R a j,Rt>i, 2, 2, a s, R&3, A 4, and 3 ⁇ 44 is CH 3 .
  • each of R a j,Rt>i, 2, 2, a s, R&3, A 4, and 3 ⁇ 44 is CH 3 .
  • each of R a j,Rt>i, 2, 2, a s, R&3, A 4, and 3 ⁇ 44 is CH 3 .
  • each of R a j,Rt>i, 2, 2, a s, R&3, A 4, and 3 ⁇ 44 is CH 3 .
  • each of R a j,Rt>i, 2, 2, a s, R&3, A 4, and 3 ⁇ 44 is CH 3 .
  • each of R a j,Rt>i, 2, 2, a s, R&3, A 4, and 3 ⁇ 44 is CH 3 .
  • each of R a j,Rt>i, 2, 2, a s, R&3, A 4, and 3 ⁇ 44 is CH 3 .
  • each of R a i, , Ra2, 3 ⁇ 4>2, a3, and 3 ⁇ 43 is CH 3 and each of R A 4 and MIS H.
  • l ⁇ is 4
  • each of R a i,Ra2, and R a3 is H and each of w , R b2 , and j
  • 3 is CH 3 .
  • R a j is H
  • M is CH 3
  • each of R a2 , 3 ⁇ 42 , Ra3. and Rj >3 is CH 3 .
  • l ⁇ 4, a j and R 3 ⁇ 4 i are H, ⁇ and 3 ⁇ 42 are CH 3 , a s and R 3 ⁇ 43 are CH 3 , and R A4 and &4 are " L .
  • R ai and M are CH 3
  • R a2 and 3 ⁇ 4 2 are CH 3 ,
  • Ra3 and Rj, 3 are CH 3
  • a and RM are ' 3 ⁇ 4 ⁇ ⁇ ,
  • Ra2 and R b2 are CH 3 , R a3 and j, 3 are .
  • a i and 3 ⁇ 4 i are CH 3
  • R a2 and b2 are CH 3
  • R A3 and RM are " 3 ⁇ 4
  • R A4 and I3 ⁇ 4 4 are ' 3 ⁇ 4 .
  • Rj > i are H, R a2 and j >2 are , R a3 and 3 ⁇ 43 are " 3 ⁇ 4 ⁇ * and Ra 4 and Rb4 are ' 3 ⁇ 4 .
  • R ai and R b i are CH 3
  • ⁇ and R b2 are " 3 ⁇ 4
  • R A3 and ⁇ * 3 are " 3 ⁇ 4
  • R A4 and RM are "* ⁇ .
  • R ai is H
  • 3 ⁇ 4 i is
  • R b i are H
  • R ⁇ and Rj, 2 are H
  • a s and 3 ⁇ 4 3 are H
  • R A4 and R b4 are ⁇ .
  • Ra2 and R B2 are H, R a3 and R B3 are CH 3 , and R a4 and M are A '3 ⁇ 4 ⁇ ⁇ c -* .
  • a i and 3 ⁇ 4 i are H, R a2 and (, 2
  • R a ⁇ and j,j are CH 3
  • R a2 and (, 2 are CH 3
  • Ra3 and RM are CH 3
  • R a4 and R3 ⁇ 4 4 are .
  • R BJ are H
  • R ⁇ and R B2 are H
  • R a3 and 3 ⁇ 43 are and R a4 and j, 4 are v.
  • R AL and w are H
  • R a2 and R b2 are CH , a s and B3 are " 3 ⁇ 4 ⁇ and R A4 and R b4 are In some variations of formula (12) described in the paragraphs above in which is 4, R a i and 3 ⁇ 4 ⁇ are CH 3 , R a2 and
  • I3 ⁇ 4 2 are CH 3 , R a3 and 3 ⁇ 4 are " ⁇ - and A4 and 3 ⁇ 4 4 are "3 ⁇ 4 ⁇
  • R ai is H
  • 3 ⁇ 4i is C3 ⁇ 4
  • R a2 and 3 ⁇ 4 2 are
  • R aJ is H
  • R 3 ⁇ 4 i is CH 3
  • R a2 is H
  • 3 ⁇ 4 2 is CH 3
  • R a3
  • Rj, 3 are 1 ⁇ 4 " ⁇ A- ⁇ and R a i and RM are 1 ⁇ 4 '3 ⁇ 4 ⁇ ⁇ ( ⁇
  • R[»i are H
  • R a2 and . b2 are ' ⁇
  • R a3 and R3 ⁇ 4 3 are and R A4 and M are ' 4 - ⁇
  • R a i and 3 ⁇ 4 i are
  • R a2 and 3 ⁇ 4 >2 are A / R a3 and s, 3 are % and R a 4 and j, 4 are 3 ⁇ 4 A 3 ⁇ 4 .
  • R a i is H
  • R b i is H
  • R a2 and 3 ⁇ 4 >2 are' 3 ⁇ 4 A
  • R a3 and R 3 ⁇ 43 are " 3 ⁇ 4 A and A4 and RM are " 3 ⁇ 4 A ⁇
  • RM are " 3 ⁇ 4 A ⁇
  • Ra2 and Rj >2 are CH 3
  • R 1(3 are CH 3
  • R a4 and R b4 are 3 ⁇ 4 '3 ⁇ 4 A ⁇ /
  • Jj is 4, R ai and R bl are R a2
  • R ⁇ are * In some variations of formula (12) described in the paragraphs above in which is 4, R a i and R l are In some vari ations of formula (12) described in the paragraphs above in which is 4, R a i and R i are * R a3 and R b3 are CH 3 , and R a4 and R b4 are In some vari ations of formula (12) described in the paragraphs above in which /; is 4, R a i and R M are
  • R b i are 3 ⁇ 4 R a2 and R b2 are ' 3 ⁇ 4 ⁇ ⁇ [276]
  • R ai and 3 ⁇ 4i are In some variations of formula (12) described in the paragraphs above in which h i s 4, a i and R3 ⁇ 4i are 0 0 o
  • Ra2 and R b2 are "3 ⁇ 4 R a3 and R b3 are CH 3 , and R a4 and Rj >4 are ⁇ .
  • R a! and R b! are 0 0 o
  • Ra2 and R b2 are ' ⁇ - R a3 and R b3 are CH 3 , and R a4 and R b4 are r ⁇
  • R a! and R b! are 0 0 o
  • Ra2 and R b2 are ' * ⁇ R a3 and 3 ⁇ 43 are H, and R a 4 and R b4 are ' 3 ⁇ 4 ⁇ f ⁇
  • R b i and R b2 are CH 3 , and R a3 and R b3 and R a4 and R b4 together are "* ⁇ [279]
  • l ⁇ is 4, a i
  • R ⁇ and R b2 are H, R ⁇ and R b2 are ' 3 ⁇ 4 ⁇ and R a3 and R b3 and R a4 and R b4 together are ⁇ 3 ⁇ 4 ⁇ .
  • R al and b i R a2 and R b2 are CH 3 , and R a3 and R b3 and R a4 and R M together are ' L x .
  • R a i is H
  • b i is
  • R a2 and R 2 are 1 ⁇ 4 "3 ⁇ 4 A and R A3 and R 3 and R A4 and R 4 together are 3 ⁇ 4 .
  • R ai and R b i are 1 ⁇ 4 "3 ⁇ 4 A and R A3 and R 3 and R A4 and R 4 together are 3 ⁇ 4 .
  • R a2 and R b2 are CH 3
  • R a3 and R b3 and R a4 and R M together are " ⁇ - .
  • R a! is H
  • R a2 and R b2 are '3 ⁇ 4 ⁇ and R A3 and B3 and R a4 and R b4 together are 3 ⁇ 4 .
  • R a2 and R b2 are 3 ⁇ 4A
  • a 3 and 3 and R A4 and B4 together are 3 ⁇ 4 ⁇ Y V
  • each of R a i and Rbi is H and , In some variations of formula (12) described in the paragraphs above in which l 2 is 2, each of Rai and R b i is H and R a2 and R b2 are O
  • each of a i and b i is CH 3 and R a2 and 2 are " 3 ⁇ 4 .
  • each of R a i and R3 ⁇ 4i is CH 3 and and R b2 O
  • M)l is CII 3 , and R a2 and 2 are " 3 ⁇ 4 , j n some variations of formula (12) described in the
  • R a2 and R b2 together are V In some variations of formula ( 12 described in the paragraphs above in which /? is 2, R ai and R b . In some variations of formula (12) described in the paragraphs above in which I? is 2, R al and 3 ⁇ 4i are * " R a2 and O
  • R al and b i are ' 3 ⁇ 4 ⁇ and R *i 2 are
  • each of R i,R b i, 3 ⁇ 4 2 , Ri is H and each of Ra3 and Ri »3 is CH 3 .
  • each of Rai,R b i, R 3 ⁇ 4 2, and Rj, 2 is CH 3 and each of Ra3 and Rs> 3 is H.
  • R a j is H and each of R a2 , R a j , R
  • each of R ai and R a2 is H and each of R a3, R M , 3 ⁇ 42 , and R
  • each of R a ⁇ , R a2 , and R a3 is H and each of w, K, and Rt, 3 is CH 3 .
  • each of R a i,R b i, Ra2, and Rt, 2 is H and ⁇ and i» 3 are ' 3 ⁇ 4 .
  • each of R a i,R b j, a 2, and Rj> 2 is CH 3 and R a3 and Rb3 are " .
  • R ai is H and each of R a2 , Rt>i, and R b2 is CH 3 , and R a and Rb3 are ⁇ .
  • each of R a i and R a2 is H and each of R b i and 3 ⁇ 42 is CH 3 , and R a3 and Rj, 3 are " 3 ⁇ 4 * " ⁇
  • each of R a i,R b i, R a2 , and j, 2 is H and R ⁇ and Rj, 3 are "3 ⁇ 4 .
  • each of R a i,R b i, Ra2, and R b2 is CH 3 and R a3 O
  • R a i and R M are ' 3 ⁇ 4 ⁇
  • R a2 and R 2 are , and each of R a3 and R b3 is H.
  • R a i and R b i are , R a2 and R 2 are ' 3 ⁇ 4 ⁇ and each of R a3 and 3 i s CH 3 .
  • R a i and i are " 3 ⁇ 4 R a2 and R b2 are ' 3 ⁇ 4 R a3 is H
  • R b3 is CH 3 .
  • R b3 is CH 3 .
  • R a2 and R b2 are X , and each of R a3 and b3 is CH 3 .
  • R a3 and b3 is CH 3 .
  • R b i are U * 3 ⁇ 4 ⁇ -U f ⁇
  • R a2 and R ⁇ are 1 ⁇ 4 ' 3 ⁇ 4 A
  • each of R a3 and b3 is H, In some variations ot

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Abstract

This disclosure describes compositions and methods for delivering and localizing repair cells, such as mesenchymal stem cells (MSCs) to the sites of tissue injuries, including cartilage injuries. This disclosure also describes methods for chondrogenic differentiation of MSCs in pellet compositions.

Description

COMPOSITIONS CONTAINING REPAIR CELLS AND CATIONIC DYES
TECHNICAL FIELD
[01] The technical field to which this disclosure relates is targeted therapeutics.
[02] Each reference cited in this disclosure is incorporated herein in its entirety.
BRIEF DESCRIPTION OF THE FIGURES
[03] FIG. 1. Photomicrographs demonstrating formation of Raj i cell pellets after incubation with 10 uM Compound 20 for 1, 5, 15, or 30 minutes.
[04] FIGS. 2A-B. Stability of Raj i cell pellets after incubation with 1 μΜ or 10 μ,Μ
Compound 20. FIG. 2A, 30 minute incubation. FIG. 2B, 5 minute incubation.
[05] FIGS. 3A-B. Photomicrographs demonstrating chondrogenic differentiation of rat bone marrow-derived mesenchymal stem cells (MSCs) after 21 days in chondrogenic medium. FIG. 3A, without Compound 20. FIG. 3B, in the presence of 10 μΜ Compound 20.
[06] FIGS. 4A-D. Photomicrographs demonstrating chondrogenic differentiation of rabbit MSCs in pellet cultures. FIG. 4A, rabbit MSCs incubated in chondrogenic medium without Compound 20. FIG. 4B, rabbit MSCs incubated in chondrogenic medium with Compound 20. FIG. 4C, rabbit MSCs incubated in basal medium without Compound 20. FIG. 4D, rabbit MSCs incubated in basal medium with Compound 20.
[07] FIGS. 5A-B. Photomicrographs demonstrating chondrogenic differentiation in pellet cultures of 100,000 rabbit MSCs after 21 days. FIG. 5A, rabbit MSCs incubated in chondrogenic medium without Compound 20. FIG. SB, rabbit MSCs incubated in chondrogenic medium with Compound 20.
[08] FIG. 6. Graph demonstrating qualitative analysis of targeting of Raji cells stained with Compound 20 on different tissues.
[09] FIG. 7. Photomicrographs demonstrating targeting of rabbit mesenchymal stem ceils (rbMSCs) incubated with Compound 20 to different organs from Balb/c mice,
[10] FIG. 8A. Photomicrographs demonstrating that Compound 4 promotes adherence of Raji cells to meniscus expiants. [11] FIG. 8B. Photomicrographs demonstrating that Compound 4 and Compound 20 (FIG. 3B) promote cell adherence of Raji cells to meniscus expiants.
[12] FIG. 9. Photomicrographs demonstrating the presence of Compound 4 in the knees of rats up to 24 hours after intra-articular injection.
[13] FIGS. 10A-B. Photomicrographs demonstrating that Compound 4 stains the small intestine (FIG. 10A) but not Peyer's patches (FIG. 10B) after oral administration.
[14] FIGS. 11A-11B. Photomicrographs demonstrating the location of safranin-0 and
Compound 4 staining in in various tissues 24 hours after oral administration. FIG. 11 A, thymus, liver, heart, lung. FIG. 11B, spleen, small intestine.
[15] FIGS. 1.2A-12B. Photomicrographs demonstrating the location of Compound 4 staining in in various tissues 24 hours after intravenous administration. FIG. 12A, spleen, heart, kidney, brain. FIG. 12B, liver, lung, bladder, blood.
Definitions
[16] "Aryl" refers to an unsaturated aromatic carbocyclic group having a single ring (e.g., phenyl) or multiple condensed rings (e.g., naphthyl or anthryl) which condensed rings may or may not be aromatic. In one variation, the aryl group contains from 6 to 14 annular carbon atoms (e.g., 6-14, 6-13, 6-12, 6-1 1, 6- 0, 6-9, 6-8, 6-7, 7-14, 7-13, 7- 2, 7-1 1, 7-10, 7-9, 7-8, 8-14, 8- 13, 8-12, 8- 1 1, 8- 10, 8-9, 9-14, 9-13, 9-12, 9-1 1, 9-10, 10-14, 10-13, 10- 12, 10-1 1, 1 1-14, 1 1-13, 1 1 -12, 12-14, 12-13, 13-14, 6, 7, 8, 9, 10, 1 1 , 12, 13, or 14). An aryl group having more than one ring where at least one ring is non-aromatic may be connected to the parent structure at either an aromatic ring position or at a non-aromatic ring position . In one variation, an aryl group having more than one ring where at least one ring is non-aromatic is connected to the parent structure at an aromatic ring position.
[17] "Heteroaryl" refers to an unsaturated aromatic carbocyclic group having from 2 to 10 annular carbon atoms (e.g., 2-10, 2-9, 2-8, 2-7, 2-6, 2-5, 2-4, 2-3, 3-10, 3-9, 3-8, 3-7, 3-6, 3-5, 3- 4, 4-10, 4-9, 4-8, 4-7, 4-6, 4-5, 5-10, 5-9, 5-8, 5-7, 5-6, 6- 10, 6-9, 6-8, 6-7, 7- 10, 7-9, 7-8, 8-10, 8-9, 9-10, 2, 3, 4, 5, 6, 7, 8, 9, or 10) and at least one annular heteroatom, including but not limited to heteroatoms such as nitrogen, oxygen and sulfur. A heteroaryl group may have a single ring (e.g., pyridyl, furyl) or multiple condensed rings (e.g., indolizinyl, benzothienyl) which condensed rings may or may not be aromatic. A heteroaryl group having more than one ring where at least one ring is non-aromatic may be connected to the parent structure at either an aromatic ring position or at a non-aromatic ring position. In one variation, a heteroaryl group having more than one ring where at least one ring is non-aromatic is connected to the parent structure at an aromatic ring position.
[18] "Cycloalkyl" is a saturated cyclic hydrocarbon structure and can consist of one ring, such as cyclohexyl, or multiple rings, such as adamantyl. A cycloalkyl comprising more than one ring may be fused, spiro or bridged, or combinations thereof. A cycloalkyl can be a saturated cyclic hydrocarbon having from 3 to 13 annular carbon atoms (e.g., 3-13, 3-12, 3-1 1 , 3-10, 3-9, 3-8, 3- 7, 3-6, 3-5, 3-4, 4-13, 4- 12, 4-1 1, 4-10, 4-9, 4-8, 4-7, 4-6, 4-5, 5- 13, 5-12, 5-1 1, 5-10, 5-9, 5-8, 5- 7, 5-6, 6-13, 6-12, 6-1 1, 6-10, 6-9, 6-8, 6-7, 7-13, 7-12, 7-1 1 , 7-10, 7-9, 7-8, 8- 13, 8-12, 8-1 1 , 8-
10, 8-9, 9- 13, 9-12, 9-1 1, 9- 10, 10-13, 10- 12, 10- 1 1, 1 1-13, 1 1- 12, 12-13, 3, 4, 5, 6, 7, 8, 9, 10,
1 1 , 12, or 13 annular carbon atoms). Examples of cycloal kyl groups include adamantyl,
decahydronaphthalenyl, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.
[19] "Heterocyclyl" refers to a saturated or an unsaturated non-aromatic group having a single ring or multiple condensed rings, and having from I to 10 annular carbon atoms (e.g., 1- 10, 1-9, 1-8, 1-7, 1 -6, 1-5, 1 -4, 1-3, 1 -2, 2-10, 2-9, 2-8, 2-7, 2-6, 2-5, 2-4, 2-3, 3-10, 3-9, 3-8, 3-7, 3-6, 3- 5, 3-4, 4-10, 4-9, 4-8, 4-7, 4-6, 4-5, 5-10, 5-9, 5-8, 5-7, 5-6, 6- 10, 6-9, 6-8, 6-7, 7-10, 7-9, 7-8, 8- 10, 8-9, 9-10, 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10) and from 1 to 4 annular heteroatoms (e.g., 1-4, 1 -3, 1- 2, 2-4, 2-3, 3-4, 1, 2, 3, o4 5), such as nitrogen, sulfur or oxygen. A heterocycle comprising more than one ring may be fused, spiro or bridged, or any combination thereof. In fused ring systems, one or more of the rings can be aryl or heteroaryl. A heterocycle having more than one ring where at least one ring is aromatic may be connected to the parent structure at either a non- aromatic ring position or at an aromatic ring position. In one variation, a heterocycle having more than one ring where at least one ring is aromatic is connected to the parent structure at a non-aromatic ring position.
[01] "Ra and ¾ (or Raj and ¾i; or Ra2 and Rt>2; or
Figure imgf000004_0001
O
means "Ra and Rj, (or RaJ and Rt>i; or Ra2 and Rj,2; or ^ and ; or Rc2 and Ry),
, , O
together with the carbon atom to which they are attached, are "^- ^ or "^- ^ ." "Ra and ¾ (or
Raj and R¾i; or Ra2 and Rj,2; or
Figure imgf000004_0002
means "Ra and j, (or Ra! and RM; or Ra2 and Ris2; or RcS and Rx; or Rc2 and RY) , together with the carbon atom to which they are attached, are ' * ^ ." "Ra and ¾ (or Rai and ¾j; or Ra2 and Rj>2; or ^ and Rx; or p
and Rv) are '¾ ^-"" means "Ra and j, (or Rai and ^; or Ra2 and R¾2; or R^ and Rx; or R^
0
RY), together with the carbon atom to which they are attached, areA r*'
[02] This disclosure describes compositions and methods for delivering and localizing repair cells to the sites of cartilage injuries, A "repair cell" as used herein includes cells which, when exposed to appropriate conditions, differentiate into an appropriate cell type for repair of a particular target tissue, as well as cells which are at least partially differentiated into the appropriate cell type for the tissue to be repaired. For example, in some variations a repair cell differentiates into a ceil which produces and secretes components needed to repair an injury to a joint (e.g., hyaline cartilage, tendon, meniscus). In some variations of the disclosed methods, a repair cell is a chondrocyte. In some variations of the disclosed methods, a repair cell is a mesenchymal stem cell (MSC). Methods of obtaining, culturing, and expanding populations of MSCs are well known in the art. See, e.g., US 2004/0009157; US 2012/0148548; U.S. Patent 5,486,359; and U.S. Patent 5,226,914. Typically, autologous MSCs are used. In some embodiments, allogenic MSCs are used (e.g., MSCs obtained from banks of umbilical cord MSCs, MHC-matched MSCs, or MSCs engineered to not have comprise immunogenic MHCs).
In the disclosed methods, a population of repair cells, e.g., M SCs, is incubated with a compound which is a cationic dye multimer, described below, under conditions sufficient for the compound to bind to the surface of the repair cells, then the population is subjected to centrifugation to form a pellet composition. A "pellet composition" as used herein, unless otherwise specified, does not imply that the pelleted have been cultured in vitro (as in the optional culture step disclosed below).
Conditions for Incubating Repair Cells with a Cationic Dye Multimer
[04] Examples of conditions sufficient for a cationic dye multimer, such as compound 4 or compound 20, to bind to the surface of cells are provided in the working examples, below. These conditions include incubation with the compound at room temperature for 1, 5, 15, or 30 minutes. Conditions for other compounds disclosed herein can readily be determined using the working examples as a starting point. [05] In some variations, the repair cells (e.g., MSCs) are incubated with a cationic dye multimer for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 minutes.
[06] In some variations, about 0.5-1 x 106 repair cells (e.g., MSCs) are incubated with a cationic dye multimer (e.g., compound 4 or compound 20). In some variations, about 105 repair cells (e.g., MSCs) are incubated with a cationic dye multimer (e.g., compound 4 or compound
20),
Pelleting the Repair Cells
[07] Pellet cultures of MSCs are known in the art (e.g., US 2003/0026786; US 2005/0019865; Bosnakovski et al., Experimental Hematology 32, 502-09, 2004; Chen et al., PLoS One 9, e9156I, 1-11, 2014; Miyanashi et al., Tissue Engineering 12, 1419-28, 2006; Ong et al.,
Biomaterials 27, 2-87-08, 2006; Kawaniura et al., Experimental Hematology 33, 865-72, 2005; Safshekan et al., Artificial Organs 36, 1065-71, 2012; Ullah et al., BioResearch Open Access 1, 297-305, 2012), and examples of suitable conditions for forming a pellet of a population of MSCs after incubation of the MSCs with a compound of formula (I) are provided in the working examples, below. Pellet cultures of other types of repair cells can be similarly prepared.
Optio al Culture of Repair Cell Pellet
[08] In some variations, the pellet is not cultured before applying the pellet to the site of the injury. In some variations, the pellet is cultured for varying periods of time before applying the pellet to the site of the injury, as described in the paragraphs below,
[09] In some variations, the pellet is cultured for 1-21 days, 1 -20 days, 1-19 days, 1 -18 days, 1-17 days, 1-16 days, 1-15 days, 1-14 days, 1-13 days, 1-12 days, 1-11 days, 1-10 days, 1-9 days, 1-8 days, 1-7 days, 1-6 days, 1 -5 days, 1-4 days, 1 -3 days, or 1-2 days. In some variations, the pellet is cultured for less than 1-21 days, 1-20 days, 1-19 days, 1-18 days, 1-17 days, 1-16 days, 1-15 days, 1-14 days, 1-13 days, 1-12 days, 1-1 1 days, 1 -10 days, 1-9 days, 1-8 days, 1-7 days,
1- 6 days, 1-5 days, 1 -4 days, 1-3 days, or 1-2 days.
[10] In some variations, the pellet is cultured for 2-21 days, 2-20 days, 2-19 days, 2-18 days,
2- 17 days, 2-16 days, 2-15 days, 2-14 days, 2-13 days, 2-12 days, 2-11 days, 2-10 days, 2-9 days, 2-8 days, 2-7 days, 2-6 days, 2-5 days, 2-4 days, or 2-3 days. In some variations, the pellet is cultured for less than 2-21 days, 2-20 days, 2-19 days, 2-18 days, 2-17 days, 2-16 days, 2-15 days, 2-14 days, 2-13 days, 2-12 days, 2-11 days, 2-10 days, 2-9 days, 2-8 days, 2-7 days, 2-6 days, 2-5 days, 2-4 days, or 2-3 days. [11] In some variations, the pellet is cultured for 3-21 days, 3-20 days, 3-19 days, 3-18 days, 3-17 days, 3-16 days, 3-15 days, 3-14 days, 3-13 days, 3-12 days, 3-11 days, 3-10 days, 3-9 days,
3- 8 days, 3-7 days, 3-6 days, 3-5 days, or 3-4 days. In some variations, the pellet is cultured for less than for 3-21 days, 3-20 days, 3-19 days, 3-18 days, 3-17 days, 3-16 days, 3-15 days, 3-14 days, 3-13 days, 3-12 days, 3-11 days, 3-10 days, 3-9 days, 3-8 days, 3-7 days, 3-6 days, 3-5 days, or 3-4 days.
[12] In some variations, the pellet is cultured for 4-21 days, 4-20 days, 4-19 days, 4-18 days,
4- 17 days, 4-16 days, 4-15 days, 4-14 days, 4-13 days, 4-12 days, 4-1 1 days, 4-10 days, 4-9 days, 4-8 days, 4-7 days, 4-6 days, or 4-5 days. In some variations, the pellet is cultured for less than 4- 21 days, 4-20 days, 4-19 days, 4-18 days, 4-17 days, 4-16 days, 4-15 days, 4-14 days, 4-13 days,
4- 12 days, 4-11 days, 4-10 days, 4-9 days, 4-8 days, 4-7 days, 4-6 days, or 4-5 days.
[13] In some variations, the pellet is cultured for 5-21 days, 5-20 days, 5-19 days, 5-18 days,
5- 17 days, 5-16 days, 5-15 days, 5-14 days, 5-13 days, 5-12 days, 5-1 1 days, 5-10 days, 5-9 days, 5-8 days, 5-7 days, or 5-6 days. In some variations, the pellet is cultured for less than 5-21 days,
5- 20 days, 5-19 days, 5-18 days, 5-17 days, 5-16 days, 5-15 days, 5-14 days, 5-13 days, 5-12 days, 5-1 1 days, 5-10 days, 5-9 days, 5-8 days, 5-7 days, or 5-6 days.
[14] In some variations, the pellet is cultured for 6-21 days, 6-20 days, 6-19 days, 6-18 days,
6- 17 days, 6-16 days, 6-15 days, 6-14 days, 6-13 days, 6-12 days, 6-11 days, 6-10 days, 6-9 days, 6-8 days, or 6-7 days. In some variations, the pellet is cultured for less than 6-21 days, 6-20 days,
6- 19 days, 6-18 days, 6-17 days, 6-16 days, 6-15 days, 6-14 days, 6-13 days, 6-12 days, 6-11 days, 6-10 days, 6-9 days, 6-8 days, or 6-7 days.
[15] In some variations, the pellet is cultured for 7-21 days, 7-20 days, 7-19 days, 7-18 days,
7- 17 days, 7-16 days, 7-15 days, 7-14 days, 7-13 days, 7-12 days, 7-11 days, 7-10 days, 7-9 days, or 7-8 days. In some variations, the pellet is cultured for less than for 7-21 days, 7-20 days, 7-19 days, 7-18 days, 7-17 days, 7-16 days, 7-15 days, 7-14 days, 7-13 days, 7-12 days, 7-1 1 days, 7- 10 days, 7-9 days, or 7-8 days.
[16] In some variations, the pellet is cultured for 8-21 days, 8-20 days, 8-19 days, 8-18 days,
8- 17 days, 8-16 days, 8-15 days, 8-14 days, 8-13 days, 8-12 days, 8-11 days, 8-10 days, or 8-9 days. In some variations, the pellet is cultured for less than 8-21 days, 8-20 days, 8-19 days, 8-18 days, 8-17 days, 8-16 days, 8-15 days, 8-14 days, 8-13 days, 8-12 days, 8-11 days, 8-10 days, or 8-9 days [17] In some variations, the pellet is cultured for 9-21 days, 9-20 days, 9-19 days, 9-18 days, 9-17 days, 9-16 days, 9-15 days, 9-14 days, 9-13 days, 9-12 days, 9-1 1 days, or 9-10 days. In some variations, the pellet is cultured for less than for 9-21 days, 9-20 days, 9-19 days, 9-18 days, 9-17 days, 9-16 days, 9-15 days, 9-14 days, 9-13 days, 9-12 days, 9-11 days, or 9-10 days.
[18] In some variations, the pellet is cultured for 10-21 days, 10-20 days, 10-19 days, 10-18 days, 10-17 days, 10-16 days, 10-15 days, 10-14 days, 10-13 days, 10-12 days, or 10-11 days. In some variations, the pellet is cultured for less than 10-21 days, 10-20 days, 10-19 days, 10-18 days, 10-17 days, 10-16 days, 10-15 days, 10-14 days, 10-13 days, 10-12 days, or 10-1 1 days.
[19] In some variations, the pellet is cultured for 11-21 days, 1 1-20 days, 11-19 days, 11-18 days, 1 1-17 days, 1 1 -16 days, 11-15 days, 11-14 days, 1 1 -13 days, or 11-12 days. In some variations, the pellet is cultured for less than 11-21 days, 11-20 days, 1 1-19 days, 11-18 days, 11- 17 days, 11-16 days, 11-15 days, 1 1 -14 days, 11-13 days, or 1 1 -12 days,
[20] In some variations, the pellet is cultured for 12-21 days, 12-20 days, 12-19 days, 12-18 days, 12-17 days, 12-16 days, 12-15 days, 12-14 days, or 12-13 days. In some variations, the pellet is cultured for less than 2-21 days, 12-20 days, 12-19 days, 12-18 days, 12-17 days, 12-16 days, 12-15 days, 12-14 days, or 12-13 days.
[21] In some variations, the pellet is cultured for 13-21 days, 13-20 days, 13-19 days, 13- 8 days, 13-17 days, 13-16 days, 13-15 days, or 13-14 days. In some variations, the pellet is cultured for less than 13-21 days, 13-20 days, 13-19 days, 13-18 days, 13-17 days, 13-16 days, 13-15 days, or 13-14 days.
[22] In some variations, the pellet is cultured for 14-21 days, 14-20 days, 14-19 days, 14-18 days, 14-17 days, 14-16 days, or 14-15 days. In some variations, the pellet is cultured for less than 14-21 days, 14-20 days, 14-19 days, 14-18 days, 14-17 days, 14-16 days, or 14-15 days,
[23] In some variations, the pellet is cultured for 15-21 days, 15-20 days, 15-19 days, 15-18 days, 15-17 days, or 15-16 days. In some variations, the pellet is cultured for less than 15-21 days, 15-20 days, 15-19 days, 1 5-18 days, 15-17 days, or 15-16 days.
[24] In some variations, the pellet is cultured for 16-21 days, 16-20 days, 16-19 days, 16-18 days, or 16-17 days. In some variations, the pellet is cultured for less than 16-21 days, 16-20 days, 16-19 days, 16-18 days, or 16-17 days. [25] In some variations, the pellet is cultured for 17-21 days, 17-20 days, 17-19 days, or 17-18 days. In some variations, the pellet is cultured for less than 17-21 days, 17-20 days, 17-19 days, or 17-18 days,
[26] In some variations, the pellet is cultured for 18-21 days, 18-20 days, or 18-19 days. In some variations, the pellet is cultured for less than 18-21 days, 18-20 days, or 18-19 days.
[27] In some variations, the pellet is cultured for 19-21 days or 19-20 days. In some variations, the pellet is cultured for less than 19-21 days or 19-20 days.
[28] In some variations, the pellet is cultured for 20-21 days. In some variations, the pellet is cultured for less than 20-21 days.
)] In some variations, the peilet is cultured for 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 21, or 21 days. In some variations, the pellet is cultured for less than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 21 , or 21 days.
[30] In some of the variations about in which the peilet, e.g., an MSG pellet, is cultured before applying it to the site of injury, the culture medium does not comprise TGF .
[31] In some of the variations about in which the peilet, e.g., an MSG pellet, is cultured before applying it to the site of injury, the culture medium compri ses TGFp.
[32] In some of the variations about in which the peilet, e.g., an MSG pellet, is cultured before applying it to the site of injury, the culture medium is a basal culture medium.
[33] In some of the variations about in which the peilet, e.g., an MSG pellet, is cultured before applying it to the site of injury, the culture medium is a chondrocyte differentiation medium.
Methods of Chondrogenic Differentiation of MSCs
[34] Using the culture conditions described above, this disclosure also provides methods of differentiating MSCs in pellet cultures which do not require the use of chondrogenic medium or ΤΙϊΡβ. See example B5, below.
Administration of a Pellet Composition to the Site of a Tissue Injury
[35] Pellet compositions comprising repair ceils can be used to treat injured or diseased tissues, including, but not limited to, pancreas, kidney, intestine (e.g., small intestine, cecum), heart, cartilage (e.g., trachea, femoral cartilage), thymus, liver, brain, bladder, blood. Administration of a Pellet Composition to the Site of a Cartilage Injury
[36] Administration of one or more pellet compositions of MSCs can be carried out during an arthroscopic or open joint procedure and can be used to treat cartilage injuries at joints such as the acromioclavicular, carpometacarpal (finger or thumb), coracoclavicular, humeroulnar, humeroradial, radioulnar (distal, intermedial, proximal), intermetacarpal, interphalangeal, metacarpophalangeal, midcarpal, radiocarpal, shoulder, sternoclavicular, wrist,
temporomandibular, sternocostal, xiphisternal, lumbosacral, sacroiliac, talocrural (ankle), hip, metatarsophalangeal, tarsometatarsal, tibiofemoral (knee) joints, and zygapophy seal joints,
[37] Types of cartilage injuries which can be treated include damage to cartilage at a synovial joint occurring as a result of mechanical destruction due to trauma or progressive degeneration (osteoarthrosis; wear and tear) or associated with a disease or disorder, such as osteoarthritis, rheumatoid arthritis, gout, reactive arthritis, psoriatic arthritis, or juvenile arthritis. Other injuries include damage to tendons, ligaments, and the meniscus. Use of tissue engineering, including stem cell therapy, to treat such injuries has been reviewed. See, e.g. Nesic, ei ai. "Cartilage Tissue Engineering for Degenerative Joint Disease," Advanced Drug Delivery Reviews (2006), 58(2): 300-322; Johnstone, et al. "Tissue Engineering for Articular Cartilage Repair - The State of the Art," European Cells and Materials (2013) 25:248-267; Dragoo, et al. "Healing Full- Thickness Cartilage Defects using Adipose-Derived Stem Cells," Tissue Engineering (2007), 13(7): 1615-1621. Use of animal models including chondral / osteochondral defects has been discussed recently. See, e.g. Cook, et al. "Animal Models of Cartilage Repair," Bone Joint Res. (2014), 4:89-94. Bone-marrow derived MSCs, as well as human embryonic stem cells, have been shown to enhance cartilage repair in chondral defect models: Frisbie, et al. "Evaluation of Intra- Articular Mesenchymal Stem Cells to Augment Healing of Microfractures Chondral Defects," Arthroscopy (2011 ), 27(11): 1552-1561; Tsaiwei, et al. "Repair of Cartilage Defects in Arthritic Tissue with Differentiated Human Embryonic Stem Cells," Tissue Engineering Part A (2014) 20(3-4):683-692.
Pharmaceutical Compositions
[38] Pellet compositions can be provided in a pharmaceutical composition comprising a pharmaceutically acceptable carrier. A "pharmaceutically acceptable carrier" carrier is a material that is not biologically or otherwise undesirable, e.g., the material may be incorporated into a pharmaceutical composition administered to an individual without causing significant undesirable biological effects or interacting in a deleterious manner with any of the other components of the composition in which it is contained. Pharmaceutically acceptable carriers meet the required standards of toxicological and manufacturing testing and/or are included on the Inactive Ingredient Guide prepared by the U.S. Food and Drug administration.
Compounds
[39] The compounds depicted herein, by virtue of their cationic nature, are typically present as salts even if salts are not depicted and thus are accompanied by a pharmaceutically acceptable counterion, forming a pharmaceutically acceptable salt. A "pharmaceutically acceptable counterion" is an ionic portion of a salt that is not toxic when released from the salt upon administration to a recipient. Pharmaceutically acceptable salts may be formed with many acids, including but not limited to hydrochloric, sulfuric, acetic, lactic, malic, succinic, hydrogen bisulfide, salicylic, tartaric, bitartaric, ascorbic, maleic, besylic, fumaric, gluconic, glucuronic, formic, glutamic, methanesulfonic, ethanesulfonic, benzenesuifonic, lactic, oxalic, para- bromophenylsulfonic, carbonic, succinic, citric, benzoic and acetic acid, and related inorganic and organic acids. Such pharmaceutically acceptable counterions thus include sulfate, pyrosulfate, bi sulfate, sulfite, bisulfate, phosphate, monohydrogenphosphate,
dihydrogenphosphate, metaphosphate, pyrophosphate, chloride, bromide, iodide, acetate, propionate, decanoate, caprylate, acrylate, formate, isobutyrate, caprate, heptanoate, propiolate, oxalate, malonate, succinate, suberate, sebacate, fumarate, maleate, butyne-I ,4-dioate, hexyne- 1,6-dioate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, hydroxybenzoate, methoxybenzoate, phthalate, terephathalate, sulfonate, xylenesulfonate, phenyl acetate, phenvlpropionate, phenvlbutyrate, citrate, lactate, β-hydroxybutyrate, glycolate, maleate, tartrate, methanesulfonate, propanesulfonate, naphthalene- 1 -sulfonate, naphtha! ene-2-sulfonate, mandelate and the like.
[40] Where tautomeric forms may be present for any of the compounds described herein, each and every tautomeric form is intended even though only one or some of the tautomeric forms may be explicitly depicted. The tautomeric forms specifically depicted may or may not be the predominant forms in solution or when used according to the methods described herein.
[41] Compounds useful for preparing pellet compositions described above are cationic dye multimers, as described below,
Cationic Dye Multimers
[42] Cationic dye multimers can be linear, branched, or cyclic. In some variations, a catiomc dye multimer is a dimer, in which two cationic dye moieties are linked with a linker as described below. In other variations, a cationic dye multimer is a trimer or higher order multimer containing, e.g., 3, 4, or 5 cationic dye moieties joined in various configurations by linkers such that the multimer is linear, branched, or cyclic. The cationic dye moieties in a multimer, as well as the linkers, can be the same or different, in various combinations, as set forth in the description below. In some embodiments, the binding capacity of a cationic dye multimer can be tuned based on the polarity /electron density of the charged multimer system such that, for example, the cationic dye multimer exhibits differential binding affinities to, e.g., cartilage and MSCs.
[43] The linker moieties comprise a multivalent, rigid or non-rigid, alky] chain containing appropriate functionality at the termini to bond with the cationic dye moieties, as also set forth in the description below. Such linkers could, for example, comprise a bivalent chain thus having a cationic dye at each end resulting in a dimer. Other combinations and configurations are similarly described herein,
Cationic Dyes
[44] In some variations, cationic dyes which can be used to make catiomc dye multimers as described herein have a planar tri-aromatic core with the potential to have a positive charge at physiological pH. Representative examples of such cationic dyes are shown below, with the "wiggle line" indicating one possible point of attachment to a linker to a dimer or higher oligomer:
Figure imgf000012_0001
[45] The amino groups on cationic dyes such as safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue are unreactive. These amino groups can however be functionalized through reactions that provide "handles" which comprise a carboxyhc acid or an amine; cationic dyes comprising such handles are referred to herein as "cationic dye moieties,"
[46] As provided in the Examples herein, synthetic routes to dyes presented herein can result in positional isomeric products, for example those shown below for Safranin:
Figure imgf000013_0001
3J-diamino-2,6-dimethyl-5-phenylphenazin-5-ium 3J-diamino-2,8-dimethyl-5-phenylphenazin-5-ium wherein as presented here a methyl group can be at the 6- or 8-position. Commercially available sources of such reagents can comprise a mixture of such regioisomers. All compounds presented herein encompass any and all derivatives from such regioisomeric dyes.
[47] Cationic dye moieties can be functionalized with the appropriately substituted linkers described below using reactions known to those skilled in the art; this is illustrated for safranin-0 in the schematic below:
Figure imgf000013_0002
1. NaH
2. HCl (deproiection)
synthetic handle
Figure imgf000013_0003
[48] For example, compounds 14, 15, 16, 17, 18, and 19 in Table 1, below, can be synthesized using terephthalic acid (CAS # 100-21-0), 2,5-pyridinedicarboxylic acid (CAS# 100-26-5), 4,5-
X. imidazoledicarboxylic acid (CAS# 570-22-9), 2-(ethoxy carbonyl)- 1 ,3 -thi azole-4-carboxyli c acid (CAS# 91 1466-96-1), 1,4-cyclohexanedicarboxylic acid (CAS# 1076-97-7), and 4-oxo- cycIopentane-l,2-dicarboxylic acid diethyl ester (CAS# 914637-96-0), respectively, as a reagent. f 49] In some cationic dye multimers in which at least one of the cationic dye multimers is safranin-O, the pendant phenyl ring of the safranin-0 is unsubstituted. In some cationic dye multimers in which at least one of the cationic dye multimers is safranin-O, the pendant phenyl ring of the safranin-O is substituted with 1-3 (e.g., 1-3, 1-2, I, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. Examples of electron-donating groups include— H2,— HR,— R2,— OH,— O",
--NHCOCH3, N I OR. --OCH3, OR, --C2H5, R and— C6H5, wherein R is C 1 -C6 linear or branched aikyi (e.g., C 1-C6, C 1-C5, C1-C4, C1-C3, C 1-C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched aikyi). Examples of electron-withdrawing groups include— -NO2,— NR3 +, halo (e.g. , F, Br, CI, I), trihalides (e.g.,— CF3,— CC13,— CBr3,— CI3),— CN,— SO3H,— COOH,— COOR, — CHO, and— COR, wherein R is C1-C6 linear or branched alkyl (e.g. , C 1-C6, C 1-C5, C 1-C4, C 1-C3, CI-C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4- C5, C4, C5-C6, C5, or C6 linear or branched alkyl).
[50] In some variations, linkers comprise a positive charge, which can be provided by a positive charged substituent such as an amino al ky] , amino heterocyclyl, or N-containing heteroaromatic group. In some variations, positively charged linkers comprise amino acids such as Lys, Arg, or His, If a rigid linker is desired, one or more aromatic rings, cycloalkyl rings, heteroaromatic rings, or heterocyclyl rings, can be used to provide rigidity. Rigidity can also be increased by restricting rotation of the linker through use of sp- or sj -hybridized carbon atoms in a chain, for example with double- or triple-bonds, keto groups, and the like, as well as by employing bulky side-chains such as, for example, gem-dialkyl groups. Linkers which can be used in cationic dye multimers include linkers (a), (a. l), (a.2), (b), (b. l), (c), (c. l), (c.2), (d), (e), (e. l), (f), (f. l), (f.2), (g), (g. l), (g.2), (h), (h. l), (h.2), (i), (1. 1 ). (i.2), (i), (j . l), (j .2), (k), (1), (1. 1), (1.2), (m), (m. l ), (n), (n. l ), (n.2), (o), (p), (q), (r), and (s), below:
Figure imgf000014_0001
ia> , in which n is 1-6, nj is 1-4, and each * is an attachment site for a cationic dye moiety ; ^3Λ } , in which η is 1-6, «/ is 1 -4, and * is an attachment site for a cationic dye moiety:
Figure imgf000015_0001
(a.2) , in which n is 1-6, n} is 1-4, and * is an attachment site for cationic dy< moiety;
Figure imgf000015_0002
, in which n is 0-6, tij is 1-4, and each * is an attachment site for a cationic dye moiety;
Figure imgf000015_0003
, in which n is 0-6, n} is 1-4, and * is an attachment site for cationic dye moiety,
Figure imgf000015_0004
, in which n is 0-6; rt is 1 -4; for each independent instance of Ra and
I¾, (1) R and Rj, independently are H or CH3, or (2) Ra and ¾ are
Figure imgf000015_0005
or O
'¾ * is an attachment site for a
Figure imgf000015_0006
H3C CH3 H3C CH3
Figure imgf000016_0001
and
Figure imgf000016_0002
in which n is 0-6; n} is 1-4; for each independent instance of Ra and
Figure imgf000016_0003
or o
or (3) two of CRaRb are X . and each * is an attachment site for a cationic dye moiety,
Figure imgf000016_0004
, in which n is 0-6, « is 1-4, for each independent instance of Ra and Rb, (1) Ra and R¾ independently are H or CH or (2) Ra and R¾ are '¾ or
Figure imgf000016_0005
and * is an attachment site for a cationic dye moiety,
Figure imgf000016_0006
(d) , where k is 2-10; for each independent instance of Ra and ¾, Ra and ¾ (1)
O
independently are H or CH3, or (2) Ra and R¾ are - ^ or '¾ f- , or (3) two of CRaRb are ; and each * is an attachment site for a cationic dye moiety;
Figure imgf000016_0007
, in which n is 0-6, ¾/ is 1-4, and each * is an attachment site for a cationic dye moiety;
Figure imgf000017_0001
('Θ· ' , in which n is 0-6, m is 1-4, and * is an attachment site for a cationic dye moiety;
Figure imgf000017_0002
(f) , in which rti is 0-5, n2 is 1-5 and each * is an attachment site for a cationic dye moiety,
Figure imgf000017_0003
( ' > , in which n} is 0-5, n2 is 1 -5 and * is an attachment site for a cationic dye moiety;
Figure imgf000017_0004
{■•2} ^ in which n} is 0-5, n2 is 1-5 and * is an attachment site for a cationic dye moiety,
Figure imgf000017_0005
(8) , in which is 0-5, n2 is 1-5 and each * is an attachment site for a cationic dye moiety,
Figure imgf000017_0006
, in which « is 0-5, !? is 1-5 and * is an attachment site for a cationic dye moiety;
Figure imgf000018_0001
te-2^ , in which tij i s 0-5, n2 is 1-5 and * is an attachment site for a cationic dye moiety;
Figure imgf000018_0002
, in which nj is 0-5, n2 is 1-5, and each * is an attachment site for a cationic dye moietv;
Figure imgf000018_0003
in- 1 / ; in which nj is 0-5, n? is 1-5, and * is an attachment site for a cationic dye moiety;
Figure imgf000018_0004
(n.z) ^ jn whjc¾ Hl js 0-53 n2 is 1-5, and * is an attachment site for a cationic dye moietv;
Figure imgf000018_0005
, in which iti and ¾ independently are 1 -5 and each * is an attachment site for a cationic dye moiety;
Figure imgf000019_0001
('·1 ) . in which it} and n2 independently are 1-5 and * is an attachment site for a cationic dye moiety;
Figure imgf000019_0002
('·2) , in which nt and n2 independently are 1 -5 and * is an attachment site for a cationic dye moiety;
Figure imgf000019_0003
, in which n2 is 1-5 and each * is an attachment site for a cationic dye moiety;
Figure imgf000019_0004
, in which n2 is 1-5 and * is an attachment site for a
cationic dye moiety;
Figure imgf000020_0001
, in which n2 is 1-5 and * is an attachment site for a cationic dye moiety:
Figure imgf000020_0002
' , in which // and h independently are 1-4, n is 1-4; ring A i s aryl, heteroaryl, cycloalkyl, or heterocvclyl; for each independent instance of Rai and ¾i, Rai and (1 independently are H or CH3, or (2) Ra! and w independently are
Figure imgf000020_0003
or (3) two of CRaiR¾i for each independent instance of a2 and Rj>2, az and j,? (1) independently are H or CH3 or (2) Ra2 and Rb2 independently are
Figure imgf000020_0004
or or (3) two of are
¾ ; and each * is an attachment site for a cationic dye moiety;
Figure imgf000020_0005
' , in which /, /?, w, and o2 independently are 1 -4; ring A is aryl, heteroaryl, cycloalkyl, or heterocycfyl; for each independent instance of ai and RM, Ra} and j,i (1) independently are H or CH3,
0
or (2) Rai and R|>i independently are " L or '¾ , or (3) two of CRaiRbi are '\ t · for each Independent instance of Ra2 and Rj,?, a2 and Rt>2 ( I )
O
independently are H or C¾, or (2) Ra2 and j,2 independently are "¾ ¾s" or ' fc ^ or (3) two of CRa2Rj,2 are ~ ¾ , for each independent instance of Rci and ¾ι, Rci and <n (1) independently are H or CH3, or (2) ^ and R<ii independently are
O
or 4 , or (3) two of CRaR<u are ^ ·; for each independent instance of Rc2 and R^, «2 and R i 0) independently are H or CH3, or (2) ¾2 and R^
O
independently are "¾ or '¾ or (3) two of C ^ ^ are and each is an attachment site for a cationic dye moiety;
Figure imgf000021_0001
ιΐ , in which «, and «¾—
1-4; ring A iiss aarryyl, . heteroaryl, cycloalkyl, or heterocyclyl; for each independent instance of Rai and RM, R nd Rbi 1) independently ar or CH3, or (2) Rai and j,i independently ar :ee
Figure imgf000021_0002
or (3) two of CRatR *ji are
each independent instance of ^ and j>2, Ra2 and Rj>21 (1) independently are H or
O
CH3, or (2) a2 and Rt>2 independently are "¾ or "% f", or (3) two of C ^ M are " 1 ; tor each independent instance ot Rci and Rai, ^ and R,n (1)
O
independently are H or CH3, or (2) R^ and Rai independently are '¾ or "^- or (3) two of C cj fj! are ¾; for each independent instance of and ¾?, R nd d2 (1) independently are H or CH3, or (2) R^ and Ri!2 independently are
Figure imgf000021_0003
for a cationic dye moiety;
Figure imgf000022_0001
(!·2^ , in which Ily l2, n, oi, and o2 independently are 1-4; ring A is aryl, heteroaryl, cycloalkyl, or heterocyclyl; for each independent instance of ai and ¾ι, Rai and ¾ι (1) independently are H or CH3 or (2) Ral and Rbi independently are
Figure imgf000022_0002
or (3) two of CRaiRw are
; for each independent instance of Ra2 and Rb2, a2 and R&2 (1) independently are H or C¾, or (2) Ra2 and R&2 independently are "¾ ^-* or
O
"¾ , or (3) two of CRa2Rb2 are ; for each independent instance of ci and Rdi, Rci and Rdj ( I) independently are H or C¾, or (2) Rd and R^i
o
independently are "¾ or '% or (3) two of CRciRdi are ¾ for each independent instance of Ι½ and ^, RC2 and (1) independently are H or CH3,
O
or (2) c2 and R^ independently -¾, f- or or i ) two of C C2 (i2 are ; and * is an attachment site for a cationic dye moiety;
Figure imgf000022_0003
, in which n is 0-6, n} is 1-4, and each * is an
attachment site for a catiomc dye moiety;
Figure imgf000022_0004
, in which n is 0-6, n} is 1-4, and * is an attachment site for a cationic dye moiety:
Figure imgf000023_0001
. in which n2 is 1-5 and each * is an attachment site for a cationic dye moiety:
Figure imgf000023_0002
Χ Λ , in which n2 is 1-5 and * is an attachment site for a cationic dye moiety;
Figure imgf000023_0003
(n 2^ , in which «2 is 1-5 and * is an attachment site for a cationic dyi moiety;
Figure imgf000023_0004
(0) , in which in which ni is 0-5, i2 is 1-5, u3 is 0-5, and * is the attachment site for a cationic dye moiety;
Figure imgf000024_0001
(P) , in which η} is 0-5, n2 is 1 -5, n3 is 0-5, and * is the attachment site for a cationic dye moiety;
Figure imgf000024_0002
(q) , in which n is 0-5, n2 is 1-5, and * is an attachment site for a cationic dye moiety:
Figure imgf000024_0003
(r) , in which nj is 0-5, n2 is 1-5, n3 is 0-5, and * is the attachment site for a cationic dye moiety: and
Figure imgf000024_0004
, in which ni is 0-5, n2 is 1-5, «j is 0-5 and * is the attachment site for a cationic dye moiety.
Cationic Dyes Comprising Linkers
[51] This disclosure also provides cationic dye moieties which comprise one or more linkers, which are suitable for preparing the conjugates and the cationic dimers disclosed herein. Cationic dyes useful for these embodiments include, but are not limited to, safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue. In some
embodiments, the cationic dye moiety is present as a monomer. In other embodiments, the cationic dye moiety is present as a multimer. In either of these embodiments, the cationic dye moiety comprises one or more linkers, which may be the same or different. Suitable linkers include, but are not limited to, linkers (a), (a. l), (a.2), (b), (b. I), (c), (c. l), (c.2), (d), (e), (e. l), (f), (f. l), (f.2), (g), (g. l), (g.2), (h), (h. l), (h,2), (i), (i. l), (i.2), (j), (j . l), (j 2), (k), (1), (1, 1), (1.2), (m), (m. l), (n), (n. l ), (n.2), (o), (p), (q), (r), and (s), described above.
Examples of Cationic Dye Dimers
Some cationic dye dimers fall within formula (1):
Figure imgf000025_0001
[53] C ) , in which each of Dl and D2 is a cationic dye moiety, n is 1-6, and «/ is 1.-4. In some variations of formula (1 ), Dl and D2 are different cationic dye moieties. In other variations of formula (1), Dl and D2 are the same cationic dye moiety. In some variations of formula (1), Dl and D2 independently are selected from the group consisting of safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue.
[54] In some variations of formula (1) described in the paragraphs above, n is 1-6, 1-5, 1-4, 1- 3, 1-2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, 5-6, I, 2, 3, 4, 5, or 6.
[55] In some variations of formula (1) described in the paragraphs above, n} is 1 -4, 1-3, 1 -2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[56] In some variations of formula (1) described in the paragraphs above, Dl is safranin-O. In some variations of formula (1) described in the paragraphs above, D2 is safranin-O. In some variations of formula (I) described in the paragraphs above, Dl and D2 are safranin-O.
[57] In some variations of formula (1) described in the paragraph above, the pendant phenyl ring of Dl is unsubstituted. In some variations of formula (1) described in the paragraph above, the pendant phenyl ring of Dl is substituted with 1-3 (e.g., 1-3, 1-2, 1, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— -NH2,— NHR,— NR2,— OH,— O",
— NHCOCH3,— NHCOR,— OCH3,—OR,— C2H5,— R, and— C&¾, wherein R is C 1-C6 linear or branched alkyl (e.g., C1-C6, C 1-C5, C1-C4, C 1-C3, C1-C2, C I , C2-C6, C2-C5, C2-
C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched aikyi). In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— -NO2,— - R3 +, halo (e.g., F, Br, CI, I), trihaiide
(e.g. , C! k— CO 3,— CBr3,— CI3),— CN, SO U I.— COOH,— COOR,— CIIO, and
— COR, wherein R is C1-C6 linear or branched al kyl (e.g., C 1 -C6, C1-C5, C 1 -C4, C 1 -C3, C l-
C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-
C6, C5, or C6 linear or branched alkyl).
[58] In some variations of formula (1) described in the paragraph above, the pendant phenyl ring of 1)2 is unsubstituted. In some variations of formula (1) described in the paragraph above, the pendant phenyl ring of D2 is substituted with 1-3 (e.g., 1-3, 1 -2, 1, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— NH2,— NHR,— NR2,— OH,— O",
--NHCOCH3,— -NHCOR, Oa k—OR, --C2H5, --R, and (\j k wherein R is C1-C6 linear or branched aikyi (e.g., C1-C6, C 1-C5, C1-C4, C 1-C3, C 1-C2, C I, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched aikyi). In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— -N02,— -NR3 +, halo (e.g., F, Br, CI, I), trihaiide (e.g., --CF3, --CCI3, --CBr3,—CI3),— CN, --SO3H,—COOH,—COOR, --CHO, and —COR, wherein R is C1-C6 linear or branched alkyl (e.g., C 1 -C6, C1-C5, C 1 -C4, C 1-C3, Cl- C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
[59] Some cationic dye dimers fall within formula (2):
Figure imgf000026_0001
, in which each of Dl and D2 is a cationic dye moiety, n is 0-6, and n} is 1-4.
[60] In some variations of formul a (2), Dl and D2 are different cationic dye moieties. In other variations of formula (2), Dl and D2 are the same cationic dye moiety. In some variations of formula (2), Dl and 1)2 are independently selected from the group consisting of safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue.
[61] In some variations of formula (2) described in the paragraphs above, n is 0-6, 0-5, 0-4, 0- 3, 0-2, 0-1 , 1-6, 1-5, 1-4, 1-3, 1 -2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, 5-6, 0, I, 2, 3, 4, 5, or 6.
[62] In some variations of formula (2) described in the paragraphs above, n} is 1-4, 1 -3, 1-2, 2-4, 2-3, 3-4, 1 , 2, 3, or 4,
[63] In some variations of formula (2) described in the paragraphs above, Dl is safranin-O. In some variations of formula (2) described in the paragraphs above, D2 is safranin-O. In some variations of formula (2) described in the paragraphs above, Dl and D2 are safranin-O.
[64] In some variations of formula (2) described in the paragraph above, the pendant phenyl ring of Dl is unsubstituted. In some variations of formula (2) described in the paragraph above, the pendant phenyl ring of Dl is substituted with 1-3 {e.g., 1-3, 1-2, 1, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of Dl is substituted, the
substituents are selected independently from— NH2,— NHR,— NR2,— OH,— O",
— NHCOCH3,— NHCOR, --OCH3,—OR,— C2¾, R, and C,l k wherein R is C1-C6 linear or branched aikyi {e.g., C1-C6, C 1-C5, C1-C4, C1-C3, C1-C2, CI, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched aikyi). In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— -N02,— -N 3 +, halo {e.g., F, Br, CI, I), trihalide {e.g.,— CF3, CCk— CBr3, Ch i.— CN, --SO3H,—COOH,— COOR,—CHO, and — COR, wherein R is C1-C6 linear or branched aikyi {e.g., C 1-C6, C1-C5, C1-C4, C 1-C3, Cl- C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
[65] In some variations of formula (2) described in the paragraph above, the pendant phenyl ring of D2 is unsubstituted. In some variations of formula (2) described in the paragraph above, the pendant phenyl ring of D2 is substituted with 1-3 {e.g., 1-3, 1 -2, 1, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of D2 is substituted, the
substituents are selected independently from— NH2,— NHR,— NR2,— OH,— O",
NHCOCH3,— -NHCOR, --OCH3,—OR, C2H5,— R, and— C6H5, wherein R is C1-C6 linear or branched alkyl (e.g., C1 -C6, C 1 -C5, C1 -C4, C 1 -C3, C1 -C2, C I, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— 02,— ΙΙι , halo (e.g., F, Br, CI, I), trihaiide (e.g.,— CF3,— CC13,— CBr3,— CI3),— CN, SO 1 I,— COOH,— COOR,— CHO, and —COR, wherein R is C1-C6 linear or branched alkyl (e.g., C 1-C6, C1-C5, C 1-C4, C 1-C3, C I - C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
Some cationic dye dimers fall within formula (3):
Figure imgf000028_0001
, in which each of Dl and D2 is a cationic dye moiety; n is 0-6, and ti is 1-4; and, for each independent instance of Ra and Rb, (1) Ra and R¾ independently are
H or CH3, or (2) Ra and Rb are "¾ or '¾ *~ tor (3) two of CRaRb are "¾- .
[67] In some variations of formula (3), Dl and D2 are different cationic dye moieties. In other variations of formula (3), Dl and 1)2 are the same cationic dye moiety. In some variations of formula (3), Dl and D2 are independently selected from the group consisting of safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue.
[68] In some variations of formula (3) described in the paragraphs above, n is 0-6, 0-5, 0-4, 0- 3, 0-2, 0-1 , 1-6, 1-5, 1-4, 1-3, 1 -2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, 5-6, 0, I, 2, 3, 4, 5, or 6.
[69] In some variations of formula (3) described in the paragraphs above, n} is 1-4, 1 -3, 1-2, 2-4, 2-3, 3-4, 1 , 2, 3, or 4,
[70] In some variations of formula (3) described in the paragraphs above in which n} is I, Ra and Rb are both H. In some variations of formula (3) described in the paragraphs above in which tii is 1, Ra is H and R¾ is CH3. In some variations of formula (3) descri bed in the paragraphs above in which ηχ is I, Ra and Rj, are both CH3. In some variations of formula (3) described in the paragraphs above in which nj is 1, Ra and & are "^- . In some variations of formula (3)
O
described in the paragraphs above in which m is 1, R¾ and R& are '¾· i .
[71] In variations of formula (3) described in the paragraphs above in which n} is 2, the two instances of Ra and ¾ are indicated as Rai and i and Ra2 and b2, respectively. In some variations of formula (3) described in the paragraphs above in which nj is 2, each of Rai and ϊ½ and Ra2 and R^ is H. In some variations of formula (3) described in the paragraphs above in which ni is 2, each of Rai and Rbi and Ra2 and ¾ι is CH3. In some variations of formula (3) described in the paragraphs above in which ¾/ is 2, each of Rai and Ra2 is H and each of w and b2 is CH3. In some variations of formula (3) described in the paragraphs above in which «z is 2, each of Ra{, Ra2, and Rbi is H and ¾2 is CH3.
[72] In some variations of formula (3) described in the paragraphs above in which n} is 2, each of Rai and Rbi is H and ^ and R1(2 are
Figure imgf000029_0001
In some variations of formula (3) described
o in the paragraphs above in which «/ is 2, each of Rai and R i is H and Ra2 and ¾2 are '¾· <"\ In some variations of formula (3) described in the paragraphs above in which n} is 2, each of Rai and bi is CH3 and Ra2 and b2 are "¾ < . In some variations of tormula (3) described in the paragraphs above in which « / is 2, each of Rai and Rbi is CH3 and Ra2 and R1(2 are ^2- .
In some variations of formula (3) described in the paragraphs above in which nj is 2, Rai is H,
Rbi is CH3, and Ra2 and b2 are '¾ . In some variations of formula (3) described in the
O
paragraphs above in which n} is 2, Rai is H, Rbi is C'l k and Ra2 and R¾2 are < . In some variations of formula (3) described in the paragraphs above in which n} is 2, ai and Rbi and Ra2 and Rb2 together are . In some variations of formula 3 described in the paragraphs above in which ¾/ is 2, Rai an . In some variations of formula (3) described in the pa
Figure imgf000029_0002
ragraphs above in which nj is 2, Ra} an O
and ¾2 are ' L . In some variations ot formula (3) described in the paragraphs above in which
O O
iii is 2, Rai and ¾i are ¾ '¾A· and Ra2 and ¾2 are ¼ <£
[73] In variations of formula (3) described in the paragraphs above in which itj is 3, the three instances of Ra and Rb are indicated as Rai and ^; Ra2 and Rj>2; and Ra3 and Rb3, respectively. In some variations of formula (3) described in the paragraphs above in which n} is 3, In some variations of formula (3) described in the paragraphs above in which ? i s 3, each of R i,Rbi, Ra2, R¾2, A3, and Rbs is H. In some variations of formula (3) described in the paragraphs above in which tii is 3, each of Rai,R i, Ra2, Rb2, Ras, and b is CH3. In some variations of formula (3) described in the paragraphs above in which n} is 3, each of Rai,Rbi, Ra2, and bj, is H and each of Ra3 and b3 is CH3. In some variations of formula (3) descri bed in the paragraphs above in which s? is 3, each of Rai,Rbi, Ra2, and Rb2, is CH3 and each of RA3 and R 3 is H. In some variations of formula (3) described in the paragraphs above in which n} is 3, Rai is H and each of Ra2, a3, bi, ¾2, and Rbs is CH3. In some variations of formula (3) described in the paragraphs above in which n} is 3, each of Rai and Ra2 is H and each of R83> RM, b2, and ¾3 is CH3. In some variations of formula (3) descri bed in the paragraphs above in which «/ is 3, each of Rai, Ra2, and as is H and each of Rbi, R&2, and B3 is CH3.
[74] In some variations of formula (3) described in the paragraphs above in which n} is 3, each of Rai,Rbi, a2, and Rb2, is II and ^ and R 3 are ^ . In some variations of formula (3) described in the paragraphs above in which n} is 3, each of Rai,Rt>i, R^, and Rb2, is CH3 and Ra3 and Rb3 are '^- . In some variations of formula (3) described in the paragraphs above in which ni is 3, Rai is H and each of Ra2, Rbi, and Rb2 is CH3, and A3 and Rb3 are "^- . In some vari ations of formula (3) described in the paragraphs above in which n} is 3, each of Rai and Ra2 is H and each of Rw and Rb2 is CH3, and Ra3 and Rb3 are
Figure imgf000030_0001
.
[75] In some variations of formula (3) described in the paragraphs above in which n} is 3,
O
each of Raj,Rbi, Ra2, and Rb2, is H and ^ and Rb3 are '¾· ^ . In some variations of formula (3) described in the paragraphs above in which tii is 3, each of Rai,Rjt>i, ¾2, and ¾2, is CH3 and R^ O
and ¾3 are '- In some variations of formula (3) described in the paragraphs above in which
O
ni is 3, Rai is H and each of R^, Rbi, and Rb2 is CH3, and a3 and Rb3 are ^ . In some variations of formula (3) described in the paragraphs above in which n} is 3, each of Rai and Ra2
O
is H and each of Rj,i and R 2 is CH3, and Ras and R¾3 are '¾· .
[76] In some variations of formula (3) described in the paragraphs above in which ηχ is 3, ai and j,i are ,¾ , Ra2 and ^ are ' 5¾1, , and each of Ra3 and b3 is H. In some variations of formula (3) described in the paragraphs above in which fij is 3, Ral and ^ are " 5^-L ^ , Ra2 and j,2 are '¾ , and each of R^ and Rb3 is (Ί I; In some variations of form (3) described in the paragraphs above in which nj is 3, ai and j>i are " ,
Figure imgf000031_0001
, as is H, and Rb3is CH3. In some variations of formu described in the paragraphs above in which «/ is 3,
Rai and R¾i are '¾ Ra2 and
Figure imgf000031_0002
and each of R¾3 and Rj,3is H. In some variations of formula cribed in the paragraphs above in which nt is 3, Ral and M are " L , Ra2 and Rb2 are
Figure imgf000031_0003
and each of a3 and j,3 is CH3. In some variations of formula (3) described in the paragraphs above in which n} is 3, ai and &i are "^- , R¾2 and ¾2 are "^- , a3 is H, and Rbsis CH3.
[77] In some variations of formula (3) described in the paragraphs above in which ηχ is 3, ai
O
and Rbi are '¾ a2 and .b2 are ' *· and each of ^ and ^ is H. In some variations of formula (3) described in the paragraphs above in which ηχ is 3, Rai and Rbi are "¾ , .a2 and
O
I b2 are , and each of Ras and I b3 is CH3. In some variations of formula (3) described in the
Q paragraphs above in which n} is 3, RaJ and j,t are "^- " , a2 and Rb2 are '¾· ¾s\ as is H, and Rb3is CH3. In some variations of formula (3) described in the paragraphs above in which ni is 3
O
Riii and M are " v¾v Ra2 and 2 are ¼ <£ and each of as and 3 is H. In some variations of formula (3) described in the paragraphs above in which s? is 3, Ra! and R¾j are "¾ ^*, A2
O
and j,2 are ' <- < , and each of A3 and &3 is CH3. In some variations of formula (3) described in the paragraphs above in which «/ is 3, Rai and R i are
Figure imgf000032_0001
, Ra3 is II, and RMIS CH3.
[78] In some variations of formula (3) described in the paragraphs above in which «/ is 3, Rai
O 0
and bi are '^- A2 and ¾2 are '¾· and each of Ra3 and ¾3 is H. In some variations of
O
formula 3) described in the paragraphs above in which n} is 3, Ral and M are '¾· Ra2 and
Rb2are
Figure imgf000032_0002
, and each of Ras and sis CH3. In some variations of formula (3) described in the
O O
paragraphs above in which n} is 3, RAJ and M are < , aa and 2 are '¾· ^\ RA3 is H, and sis CH3. In some variations of formula (3) described in the paragraphs above in which n} is 3,
Rai and i are
Figure imgf000032_0003
and each of and 3 is H. In some variations of
O
formula (3) described in the paragraphs above in which nj is 3, Rai and i are Ra2 and
Rb2are *¾ X· "^, and each of and sis CH3. In some variations of formula (3) described in the
O 0
¼A j
paragraphs above in which n} is 3, RAJ and i are aa and 2 are U -U *~, RA3 is H, and bsis CH3.
] In some variations of formula (3) described in the paragraphs above in which ¾/ is 3, RAL and bi and Ra2 and 2 together are - and each of RA3 and 3 is H. In some variations of formula (3) described in the paragraphs above in which n} is 3, RAL and M and R^ and Rb2 together are "¾ and each of as and Rb3 is CH3. In some variations of formula (3) described in the paragraphs above in which ¾/ is 3, ai and Rbi and Ra? and Rj>2 together are
' τ- A3 is H, and ¾3 is CH3. In some variations of formula (3) described in the paragraphs above in which w/ is 3, Rai and R^i and a2 and bi together are ' τ , and aj and RM are
In some variations of formula (3) described in the paragraphs above in which n is 3, Rai
9
and jji and Ra2 and R¾2 together are ^ and and R¾3 are .
[80] In variations of formula (3) described in the paragraphs above in which n} is 4, the three instances of Ra and j, are indicated as Rai and !¾; Ra2 and Κ¾2; Ras and R43; and RA4 and R¾4, respectively. In some variations of formula (3) described in the paragraphs above in which ηχ is 4, In some variations of formula (3) described in the paragraphs above in which Hi is 4, each of Rai,Rj,j, Ra2, fc2, Ras, ¾3. ¾4- and M is H. In some variations of formula (3) described in the paragraphs above in which nj is 4, each of Rai,Rbi, Ra2, Rb2, a3, ¾3, a4, and ¾4 is CH3. In some variations of formula (3) described in the paragraphs above in which n} is 4, each of Rai, ex, a2, R¾2, a , and R^ is H and each of A4 and R^ is CH3. In some variations of formula (3) described in the paragraphs above in which nj is 4, each of Rai, Rbi, Ra2, and 2 is H and each of Ra3, R*3, A4, and 4 is CH3. In some variations of formula (3) described in the paragraphs above in which n} is 4, each of Rai, Rbi, Ra2, ¾2, Ras, and ^ i s CH3 and each of A4 and ¾4 is H.
[81] In some variations of formula (3) described in the paragraphs above in which is 4, each of Rai,Ra2, and A3 is H and each of Rbi, ^, and j,3 is CH3. In some variations of formula (3) described in the paragraphs above in which n} is 4, Rai is H, RM is CH3, and each of Ra2, R 2, Ra3. and Rj>3 is CH3. In some variations of formula (3) described in the paragraphs above in which m is 4, Rai is H, i is CH3, and each of Ra2, Rb2, Ra3, and ¾3 is H. In some variations of formula (3) described in the paragraphs above in which n} is 4, each of Rai and Ra2 is H, each of Rw and Rb2 is CH3, and each of Ras and Rb3 is H. In some variations of formula (3) described in the paragraphs above in which rij is 4, each of Rai and Ra2 is H, each of w and Rt>2 is CH3, and each of Ra3 and R¾3 is CH3.
[82] In some variations of formula (3) described in the paragraphs above in which n > i s 4, Rai and Rbi are H, Ra2 and R«2 are H, A and ^ are H, and RA4 and j, are . In some variations of formula (3) described in the paragraphs above in which ttj is 4, Rai and are H,
Ra2 and R¾2 are H, Ra3 and R¾3 are CH3, and RA4 and RM are
Figure imgf000034_0001
. In some variations of formula (3) described in the paragraphs above in which n,- is 4, ai and M are H, Ra2 and j>2 are CH3, aj and Rt>3 are CH3, and Ra4 and ¾4 are "^- . In some variations of formula (3) described in the paragraphs above in which «/ is 4, Rai and R^ are CH3, 32 and ¾2 are CH3
Ra3 and ¾3 are CH3, and RA4 and RM are "
[83] In some variations of formula (3) described in the paragraphs above in which n > i s 4, Rai
Figure imgf000034_0002
and jji are H, , In some variations of formula (3) described in the paragraphs above in which n is 4, Rai and M are H,
Ra2 and Rb2 are CH3, Ra3 and Rj,3 are and Ra4 and M are "^- . In some variations of formula (3) described in the paragraphs above in which «,· is 4, Rai and jji are CH3, and Rb2
Figure imgf000034_0003
are CH3, In some variations of formula (3) described in the paragraphs above in which «/ is 4, Raj is H, RJ,J is CH3, Ra2 and Rj,2 are CH3, lb3 are "¾ and Rj,4 and ¾4 are '¾ ^ . In some variations of formula (3) described in the paragraphs above in which n} is 4, RAS is H, M is CH3, RA2 is H, Rb2 is CH3, RA and R1(3
Figure imgf000034_0004
Ra4 and Rj,4 are '¾ . [84] In some variations of formula (3) described in the paragraphs above in which n} is 4, Rai and jji are H, R^ and R¾2 are " V¾Si Ra3 and R 3 are ' V¾-%£ and RA4 and RM are si . In some variations of formula (3) described in the paragraphs above in which η, · is 4, ai and M are CH3, Ra2 and ¾ are " V¾Si Ra3 and j,3 are Hi and Ra and b4 are S ^£\ In some variations of formula (3) described in the paragraphs above in which «,· is 4, Ral is H, Rbi is
Figure imgf000034_0005
CH3, RA2 and ¾2 are "*· RA and R1(3 are "^- and A4 and R¾4 are , In some variations of formula (3) described in the paragraphs above in which n,- is 4, RAI and M are are Ra3 and I¾3 are , and A4 and i>4 are [85] In some variations of formula (3) described in the paragraphs above in which rij is 4, Rai p
and Rbi are H, Ra2 and Rj>2 are H, Ra3 and I¾3 are H, and R¾ and I M are ¼ "*A· . In some variations of formula (3) described in the paragraphs above in which ri ; is 4, Ral and BI are H,
O
Ra2 and j,2 are H, Ra3 and Rt>3 are CH3, and Ra4 and Ri i are "^- . In some variations of formula (3) described in the paragraphs above in which η,· is 4, Rai and Rj,i are H, Ra2 and j,2
O
are CH3, ^ and j,3 are CH3, and Ra4 and R¾4 are '¾· , In some variations of formula (3) described in the paragraphs above in which nj is 4, Ra} and ^i are CH3, Ra2 and R^ are CH3,
RA3 and ¾3 are CH3, and A4 and R¾4 are
Figure imgf000035_0001
[86] In some variations of formula (3) described in the paragraphs above in which « is 4, Raj
O
and Rbi are H, Ra2 and Ri,2 are H, Ra3 and ¾>3 are '¾· ^\ and Ra4 and Rb4 are v. In some variations of formula (3) described in the paragraphs above in which ttj is 4, ai and are H,
O O
%A %A
Ra2 and (,2 are CH3, Ra3 and Rj,3 are and RA4 and &4 are ^\ In some variations of formula (3) described in the paragraphs above in which ttj is 4, Rai and ^i are CH3, ^ and Rb2
O O
% A <*
are CH3, A3 and Rb3 are and Ra4 and ϊ¾4 are '^- . In some variations of formula (3 ) described in the paragraphs above in which n} is 4, RaS is H, RM is C¾, Ra2 and Rb2 are CH3,
O O
Ra3 and j,3 are and Ra4 and j>4 are ^\ In some variations of formula (3 ) described in the paragraphs above in which /?/ is 4, Ra} is H,
Figure imgf000035_0002
are
Figure imgf000035_0003
[87] In some variations of formula (3) described in the paragraphs above in which «,< is 4, Ra3
Figure imgf000035_0004
variations of formula (3) described in the paragraphs above in which η}_ is 4, Rai and bi are
0 0 o
¾A A A
CH3, Ra2 and ¾>2 are ^\ Ra3 and KB3 are ^\ and Ra4 and Rb4 are ¾ . In some variations of formula (3) described in the paragraphs above in which ttj is 4, Rai is H, R i is
0 0 o
( '! . Rai and ¾2 areA RA3 and RB3 are ¾ i and RA4 and ¾4 are Α In some variations
O
of tormula (3) described in the paragraphs above in which «7 is 4, RAI and ¾ι are ¼A ^*. A2 and
0 0 0
Rb2 are f\ RA3 and B3 are '¾A· ^ and RA4 and M are "lA f\
[88] In some variations of formula (3) described in the paragraphs above in which rij is 4, ai — y O and RM are ^*, A2 and B2 are H, R¾3 and B3 are H, and Ra4 and ¾4 are *"¾· In some variations of formula (3) described in the paragraphs above in which n ,- is 4, RAL and M are
O
"¾ Ra2 and Rb2 are CH3, Raj and ¾3 are CH3, and 34 and R¾4 are f\ In some variations of formula (3) described in the paragraphs above in which m is 4, RaJ and ¾ι are " Ra2
O
¼As s
and Rj,2 are H, Ra3 and B3 are CH3, and RA4 and Rb4 are ' 1 ^ ,
[89] In some variations of formula (3) described in the paragraphs above in which «,< is 4, Ra3
~7 v™7 O and Rbi are "^- Ra2 and Rb2 are "Q a3 and 3 are H, and Ra4 and Rb are '¾A· In some variations of formula (3) described in the paragraphs above in which n} is 4, Ral and RM are
Figure imgf000036_0001
In some variations of formula (3) described in the paragraphs above in which η}_ is 4, Rai and R i are
Figure imgf000036_0002
. In some variations of formula (3) described in the paragraphs above in which ttj is 4, ai and Rbl are
" ¾¾ , Ra2 and Rb2 are " ¾ , Ra3 and Rb3 are H, and Ra4 and Rb4 are
Figure imgf000036_0003
.
[90] In some variations of formula (3) described in the paragraphs above in which n > i s 4, Rai and Rbi are
Figure imgf000036_0004
In some variations of formula (3) described in the paragraphs above in which m is 4, Rai
Figure imgf000037_0001
and RJ>I are In some variations of formula (3) described in the paragraphs above in which rii is 4, Ral and R¾i are
Figure imgf000037_0002
In some variations of formula (3) described in the paragraphs above in which η,· is 4, Ra} and Rt, i are -j O O
¾A ¾A
" <- Ra2 and RI)2 are ' *· Ra3 and R|, are CH3, and Ra.i and Rb< are f\ in some variations of formula (3) described in the paragraphs above in which ft i is 4, R¾j &nd R¾ i fti*c
Figure imgf000037_0003
,
1 21 in some variations of formula (3) described in the paragraphs above in which «/ is 4, Ra!
^— 7 O — Q
V*V ¾^
and Rbi are ^\ Ra2 and Rb2 are · , Ra3 and Rb3 are f" , and Ra4 and RM are ^ 4. \
[93] In some variations of formula (3) described in the paragraphs above in which n < i s 4, Rai and Rj,i are
Figure imgf000037_0004
In some variations of formula (3) described in the paragraphs above in which ti t is 4, Rai and bi are
Figure imgf000037_0005
In some variations of formula (3) described in the paragraphs above in which n -< is 4, RDI and ¾,Ϊ are
Figure imgf000037_0006
n some variations of formula (3) described in the paragraphs above in which ns is 4, Rai and R ! are
Figure imgf000037_0007
.
[94] In some variations of formula (3) described in the paragraphs above in which nj is 4, ai and bi are
Figure imgf000037_0008
[95] In some variations of formula (3) described in the paragraphs above in which rij is 4, Rai and Rj>i are H, Ra2 and Rj>2 are H, and Ras and ^ and A4 and ¾4 together are '¾ . In some variations of formula (3) described in the paragraphs above in which n} is 4, Ra! and ΚΜ are II, R^ and ^ are CH3, and Raa and R 3 and A and j,4 together are " <~ V in some variations of formula (3) described in the paragraphs above in which η,· is 4, Ra} and a2 are H,
Rex and j,2 are (Ί f and as and j,3 and A4 and R¾4 together are x .
[96] In some variations of formula (3) described in the paragraphs above in which rij is 4, Rai and Rj,i are H, R^ and Rj,2 are
Figure imgf000038_0001
and RA3 and R3 and A and R together are '^- , In some variations of formula (3) described in the paragraphs above in which «_,< is 4, aj and &j
Figure imgf000038_0002
, Ra2 and j,2 are CH3, and A3 and Rj,3 and A4 and &4 together are - . In some variations of formula (3) described in the paragraphs above in which n,- is 4, Rai is H, R¾i is
Figure imgf000038_0003
CH3, a2 and ¾2 are " N^
[97] In some variations of formula (3) described in the paragraphs above in which n} is 4, RAL
O
and Rbi are H, Ra2 and j,2 are '¾· and aj and ¾3 and A4 and ^ together are . In some variations of formula (3) described in the paragraphs above in which rij is 4, RA! and &j O
are ' <■ ¾ , RA2 and s,2 are CH3, and A3 and Rj,3 and RA4 and Rj,4 together are '<· . In some variations of formula (3) described in the paragraphs above in which n,- is 4, Rai is H, R¾i is
O CH3, Ra2 and Rj,2 are A '
*" , and RA3 and RB3 and RA4 and B4 together are x V
[98] In some variations of formula (3) described in the paragraphs above in which n} is 4, Ral
O O
and j>i are ¾ A / a2 and ¾2 are '¾·^f and ^ and j,? and A4 and M together are "x . In some variations of formula (3) described in the paragraphs above in which n< is 4, at and RM
O s— y
are '^- <* Ra2 and R 2 are '¾ and A3 and R3 and RA and R together are ' *· , In some variations of formula (3) described in the paragraphs above in which Hi is 4, ai and R i O O
are · , a2 and R¾2 are '^- and RA3 and RB3 and RA4 and RB4 together are ¾
[99] In some variations of formula (3) described in the paragraphs above in which n} i s 4, RAS and RM a
Figure imgf000039_0001
nd Rb2 are and R^ and R¾3 and RA4 and Rb4 together are
In some variations of formula (3) described in the paragraphs above in which «,< is 4, Ra3 bi and Ra2 and Rb2 together are - and Raj and RM and A4 and RB4 together are
[101] In some variations of formula (3) described in the paragraphs above, Dl is safranin-O. In some variations of formula (3) described in the paragraphs above, 1)2 is safranin-O. In some variations of formula (3) described in the paragraphs above, Dl and D2 are safranin-O.
In some variations of formula (3) described in the paragraph above, the pendant phenyl ring of Dl is unsubstituted. In some variations of formula (3) described in the paragraph above, the pendant phenyl ring of Dl is substituted with 1-3 (e.g., 1-3, 1 -2, 1, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— NH2,— -NHR,— NR2,— OH,— O",
— NHCOCH3,— NHCQR,— OCH3,— OR,— C2H5,— , and—C6H5, wherein R is C 1-C6 linear or branched alkyl (e.g., C 1 -C6, C 1 -C5, C 1 -C4, C 1 -C3, C1 -C2, C I, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— N02,— R3 +, halo (e.g. , F, Br, CI, I), trihalide (e.g. ,— CF3,— CCI3,— CBr3, ('! =},— CN, SO 1 1,— COOH,— COOR,— CHO, and —COR, wherein R is C1-C6 linear or branched alkyl (e.g., C 1-C6, C1-C5, C 1-C4, C 1-C3, Cl - C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
[103] In some variations of formula (3) described in the paragraph above, the pendant phenyl ring of D2 is unsubstituted. In some variations of formula (3) described in the paragraph above, the pendant phenyl ring of 1)2 is substituted with 1-3 (e.g., 1-3, 1 -2, 1, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of D2 is substituted, the
substituents are selected independently from— NH2,— -NHR,— -NR2,— OH,— O",
— NHCOCH3,— HCOR, ΟΠ I :.— OR,— C2H5,— , and G.l k wherein R is C1-C6 linear or branched alkyl (e.g., C1 -C6, C1-C5, C1-C4, C1 -C3, C1-C2, CI, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— N02,— R3 +, halo (e.g., F, Br, CI, I), trihaiide (e.g., CF3, --CCI3, --CBr3, --CI3),— CN, -- SO3H, --COOH,—COOR,—CHO, and — COR, wherein R is C1-C6 linear or branched alkyl (e.g., C 1-C6, C1-C5, C1-C4, C 1-C3, CI- C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
Some cationic dye dimers fall within formula (4):
Figure imgf000040_0001
'4 , in which each of Dl and D2 is a cationic dye moiety; k is
2-10 and, for each independent instance of Ra and Rb, Ra and Rt> (1) independently are H or
CH3, or (2) Ra and Rb are "¾ or '¾ ? or (3) two of CRaRb are " ,
[105] In some variations of formula (4), Dl and D2 are different cationic dye moieties. In other variations of formula (4), Dl and 1)2 are the same cationic dye moiety. In some variations of formula (4), Dl and D2 are independently selected from the group consisting of safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue.
[106] In some variations of formula (4) described in the paragraphs above, k is 2-10, 2-9, 2-8, 2-7, 2-6, 2-5, 2-4, 2-3, 3-10, 3-9, 3-8, 3-7, 3-6, 3-5, 3-4, 4-10, 4-9, 4-8, 4-7, 4-6, 4-5, 5-10, 5-9, 5- 8, 5-7, 5-6, 6-10, 6-9, 6-8, 6-7, 7-10, 7-9, 7-8, 8-10, 8-9, 9-10, 2, 3, 4, 5, 6, 7, 8, 9, or 10.
[107] In some variations of formula (4) described in the paragraphs above, each Ra is H and each Rb is H. In some variations of formula (4) described in the paragraphs above, each Ra is H and each Rj, is CH3. In some variations of formula (4) described in the paragraphs above, each Ra and R& is . In some variations of formula (4) described in the paragraphs above, each O
Ra and R1( is " A¾ t . In some variations of formula (4) described in the paragraphs above, each two of CRaRb are
)8] In some variations of formula (4) described in the paragraphs above, in a first occurrence of Ra and Rb, each of Ra and R¾ is H, and the remaining occurrences of Ra and R¾ are as defined above for formula (4). In some variations of formula (4) described in the paragraphs above, in a first occurrence of Ra and Rb, each of Ra and is CH3, and the remaining occurrences of Ra and i, are as defined above for formula (4). In some variations of formula (4) described in the paragraphs above, in a first occurrence of Ra and R¾, a first Ra is H, a first R1( is CH3, and the remaining occurrences of Ra and Rb are as defined above for formula (4). In some variations of formula (4) described in the paragraphs above, in a first occurrence of R* and Rb, Ra and ¾ are
'¾ < , and the remaining occurrences of Ra and ¾ are as defined above for formula (4). In some variations of formula (4) described in the paragraphs above, in a first occurrence of Ra and
A
b, Ra and ¾ are ^ and the remaining occurrences of Ra and Rb are as defined above for formula (4).
)9] In some variations of formula (4) described in the paragraphs above, in two occurrences of Ra and Rb, each of Ra and Rj> is H, and the remaining occurrences of Ra and ¾ are as defined above for formula (4). In some variations of formula (4) described in the paragraphs above, in two occurrences of Ra and ¾, each of Ra and R¾ is CH3, and the remaining occurrences of Ra and Ri, are as defined above for formula (4). In some variations of formula (4) described in the paragraphs above, in two occurrences of Ra and ¾, two of Ra are H, two of Rb are CH3, and the remaining occurrences of Ra and Rb are as defined above for formula (4). In some variations of formula (4) described in the paragraphs above, in two occurrences of Ra and ¾, Ra and Rj, are
"¾ f", and the remaining occurrences of Ra and ¾ are as defined above for formula (4). In some variations of formula (4) described in the paragraphs above, in two occurrences of Ra and
A
Rb, Ra and ¾ are and the remaining occurrences of Ra and ¾ are as defined above for formula (4). [110] In some variations of formula (4) described in the paragraphs above, in three occurrences of Ra and Rb, each of Ra and Rj, is H, and the remaining occurrences of Ra and ¾ are as defined above for formula (4). In some variations of formula (4) described in the paragraphs above, in three occurrences of Ra and , each of Ra and is CH3, and the remaining occurrences of Ra and Ri» are as defined above for formula (4). In some variations of formula (4) described in the paragraphs above, in three occurrences of Ra and , three of Ra are H, three of Rb are O . and the remaining occurrences of Ra and Rj, are as defined above for formula (4). In some variations of formula (4) described in the paragraphs above, in three occurrences of Ra and Rb, Ra and 1¾>
Figure imgf000042_0001
and the remaining occurrences of Ra and R¾ are as defined above for formula (4), In some variations of formula (4) described in the paragraphs above, in three occurrences of Ra and
¾, a and are
Figure imgf000042_0002
and the remaining occurrences of Ra and are as defined above for formula (4).
[I ll] In some variations of formula (4) described in the paragraphs above, in four occurrences of Ra and Rb, each of Ra and b is H, and the remaining occurrences of Ra and ¾ are as defined above for formula (4). In some variations of formula (4) described in the paragraphs above, in four occurrences of Ra and Rb, each of Ra and Rb is CH3, and the remaining occurrences of Ra and b are as defined above for formula (4). In some variations of formula (4) described in the paragraphs above, in four occurrences of Ra and R , four of Ra are H, four of Rb are CH3, and the remaining occurrences of Ra and are as defined above for formula (4). In some variations of formula (4) described in the paragraphs above, in four occurrences of Ra and Rb, Ra and Rb
Figure imgf000042_0003
and the remaining occurrences of Ra and Rb are as defined above for formula (4), In some variations of formula (4) described in the paragraphs above, in four occurrences of Ra and
Rb, Ra and b
Figure imgf000042_0004
and the remaining occurrences of Ra and b are as defined above for formula (4).
[112] In some variations of formula (4) described in the paragraphs above, in five occurrences of Ra and Rb, each of Ra and Rb is H, and the remaining occurrences of Ra and R are as defined above for formula (4). In some variations of formula (4) described in the paragraphs above, in five occurrences of Ra and Rb, each of Ra and R is CH3, and the remaining occurrences of Ra and b are as defined above for formula (4). In some variations of formula (4) described in the paragraphs above, in fi ve occurrences of Ra and , fi ve of Ra are H, fi ve of Rb are C¾, and the remaining occurrences of Ra and R¾ are as defined above for formula (4), In some variations of formula (4) described in the paragraphs above, in five occurrences of Ra and j,, Ra and Rb are
Figure imgf000043_0001
the remaining occurrences of Ra and Rj> are as defined above for formula (4). In some variations of formula (4) described in the paragraphs above, in fi ve occurrences of Ra and
Q
Rb, Ra and j, are and the remaining occurrences of Ra and Rb are as defined above for formula (4).
[113] In some variations of formula (4) described in the paragraphs above, in six occurrences of Ra and R¾, each of Ra and Rj, is H, and the remaining occurrences of Ra and Rj, are as defined above for formula (4), In some variations of formula (4) described in the paragraphs above, in six occurrences of Ra and Rb, each of Ra and Rb is C¾, and the remaining occurrences of Ra and Rj, are as defined above for formula (4). In some variations of formula (4) described in the paragraphs above, in six occurrences of Ra and Rb, six of Ra are H, six of Rb are CH3, and the remaining occurrences of Ra and R1( are as defined above for formula (4), In some variations of formula (4) described in the paragraphs above, in six occurrences of Ra and Rb, Ra and Rj, are
Figure imgf000043_0002
the remaining occurrences of Ra and Rb are as defined above for formula (4). In some vari ations of formula (4) described in the paragraphs above, in six occurrences of Ra and
Rb, Ra and Rb are
Figure imgf000043_0003
and the remaining occurrences of Ra and Rj, are as defined above for formula (4).
[114] In some variations of formula (4) described in the paragraphs above, in seven occurrences of Ra and Rb, each of Ra and Rb is H, and the remaining occurrences of Ra and ¾ are as defined above for formul a (4), In some vari ations of formula (4) described in the paragraphs above, in seven occurrences of Ra and , each of Ra and is ( I f and the remaining occurrences of Ra and Rb are as defined above for formula (4). In some variations of formula (4) described in the paragraphs above, in seven occurrences of Ra and Rb, seven of Ra are H, seven of Rb are CH3, and the remaining occurrences of Ra and are as defined above for formula (4). In some variations of formula (4) described in the paragraphs above, in seven occurrences of Ra and ,
Ra and R ar
Figure imgf000043_0004
and the remaining occurrences of Ra and b are as defined above for formula (4). In some variations of formula (4) described in the paragraphs above, in seven occurrences of Ra and R , R* and Rb are
Figure imgf000044_0001
and the remaining occurrences of Ra and Rb are as defined above for formula (4).
[115] In some variations of formula (4) described in the paragraphs above, in eight occurrences of Ra and Rj,, each of Ra and R is H, and the remaining occurrences of Ra and 1¾ are as defined above for formula (4), In some variations of formula (4) described in the paragraphs above, in eight occurrences of Ra and Rb, each of Ra and Rb is CH3, and the remaining occurrences of Ra and Rj, are as defined above for formula (4). In some variations of formula (4) described in the paragraphs above, in eight occurrences of Ra and Rb, eight of Ra are H, eight of Rb are CI¾, and the remaining occurrences of Ra and Rb are as defined above for formula (4). In some variations of formula (4) described in the paragraphs above, in eight occurrences of Ra and Rb, Ra and Rb
Figure imgf000044_0002
and the remaining occurrences of Ra and R¾ are as defined above for formula (4). In some variations of formula (4) described in the paragraphs above, in eight occurrences of Ra and
Rb, Ra and Rb are
Figure imgf000044_0003
and the remaining occurrences of Ra and Rb are as defined above for formula (4).
[116] In some variations of formula (4) described in the paragraphs above, in nine occurrences of Ra and Rb, each of Ra and Rb is H, and the remaining occurrences of Ra and Rb are as defined above for formula (4). In some variations of formula (4) described in the paragraphs above, in nine occurrences of Ra and R , each of Ra and Rb is CH3, and the remaining occurrences of Ra and Rb are as defined above for formula (4). In some variations of formula (4) described in the paragraphs above, in nine occurrences of Ra and Rb, nine of Ra are H, nine of Rb are CH3, and the remaining occurrences of Ra and Rb are as defined above for formula (4). In some variations of formula (4) described in the paragraphs above, in nine occurrences of Ra and Rb, Ra and R
Figure imgf000044_0004
and the remaining occurrences of Ra and Rb are as defined above for formula (4). In some variations of formula (4) described in the paragraphs above, in nine occurrences of Ra and
R , Ra and Rb are
Figure imgf000044_0005
and the remaining occurrences of Ra and Rb are as defined above for formula (4).
[117] In some variations of formula (4) described in the paragraphs above, in ten occurrences of Ra and Rb, each of Ra and Rb is H, and the remaining occurrences of Ra and R are as defined above for formula (4), In some variations of formula (4) described in the paragraphs above, in ten occurrences of Ra and Rb, each of Ra and Rb is CH3, and the remaining occurrences of Ra and Rj, are as defined above for formula (4). In some variations of formula (4) described in the paragraphs above, in ten occurrences of Ra and Rj,, ten of Ra are H, ten of Rb are CH3, and the remaining occurrences of Ra and R1( are as defined above for formula (4), In some variations of formula (4) described in the paragraphs above, in ten occurrences of Ra and I¾>, Ra and Rb are
Figure imgf000045_0001
the remaining occurrences of Ra and Rb are as defined above for formula (4). In some variations of formula (4) described in the paragraphs above, in ten occurrences of Ra and
Rb, Ra and are
Figure imgf000045_0002
and the remaining occurrences of Ra and Rb are as defined above for formula (4).
[118] In some variations of formula (4) described in the paragraphs above, two occurrences of
Ra and I¾ are z , and the remaining occurrences of Ra and b are as defined above for formula (4). In some variations of formula (4) described in the paragraphs above, four occurrences of Ra and Rb are , and the remaining occurrences of Ra and Rb are as defined above for formula (4). In some variations of formula (4) described in the paragraphs above, six occurrences of Ra and ¾ are and the remaining occurrences of Ra and Rb are as defined above for formula (4). In some variations of formula (4) described in the paragraphs above, eight occurrences of Ra and are ¾ and the remaining occurrences of Ra and R1( are as defined above for formula (4). In some variations of formula (4) described in the paragraphs above, ten occurrences of Ra and Rb are 1 .
[119] In some variations of formula (4) described in the paragraphs above, Dl is safranin-O. In some variations of formula (4) described in the paragraphs above, D2 is safranin-O. In some variations of formula (4) described in the paragraphs above, Dl and D2 are safranin-O.
[120] In some variations of formula (4) described in the paragraph above, the pendant phenyl ring of Dl is unsubstituted. In some variations of formula (4) described in the paragraph above, the pendant phenyl ring of Dl is substituted with 1-3 (e.g., 1-3, 1 -2, 1, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— H2,— -NHR,— -NR2,— OH,— O",— NHCOCH3,— -NHCOR, --OCH3, OR, --C2H5,—R, and ---C6H5, wherein i s C1 -C6 linear or branched alkyl (e.g., C 1-C6, C1-C5, C 1-C4, C1-C3, C1-C2, C I, C2-C6, C2-C5, C2-C4, C2- C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— N02,— NR3 +, halo (e.g., F, Br, CI, I), trihalide (e.g.,— CF3, --CCI3,— CBr3, --CI3),— CN,— S03H, --CQOH,— COOR,—CHO, and —COR, wherein R is C1-C6 linear or branched alkyl (e.g., C 1-C6, C1-C5, C1-C4, C 1-C3, Cl- C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
[121] In some variations of formula (4) described in the paragraph above, the pendant phenyl ring of D2 is unsubstituted. In some variations of formula (4) described in the paragraph above, the pendant phenyl ring of 1)2 is substituted with 1-3 (e.g., 1-3, 1 -2, 1, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— NH2,— -NHR,— -NR2,— OH,— O",
— HCOCH3,— HCOR, GO I : .— OR,— C2¾,— , and— C6H5, wherein R is C1-C6 linear or branched alkyl (e.g., C1 -C6, C 1 -C5, C1 -C4, C 1 -C3, C1 -C2, C I, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— N02,— NR3 +, halo (e.g., F, Br, CI, I), trihalide (e.g.,— CF3, --CCI3, --CBr3, --CI3),— CN, SO I i, --COOH, COOR. CI 10, and —COR, wherein R is C1-C6 linear or branched alkyl (e.g., C 1-C6, C1-C5, C 1-C4, C 1-C3, Cl - C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
[122] In some of the variations of formula (4) described above, Dl and D2 are safranin-0 moieties, as shown in formula (4a):
Figure imgf000046_0001
, in which k, Ra, and Rj, are as described in the paragraphs above, Ri, R2, R3, Ri, R¾, and Rg independently are absent or independently are selected from— -NH2,— NHR,— NR2,— OH,— O",— 'NHCOCH3,
— NHCOR,— OCH3,—OR, CM k— R,— C6H5,— N02,— R3 +, halo (e.g., F, Br, CI, I), triha!ide (e.g. , Π\— CC ,— CBr3, C h i— CN,— S03H,— COOH,— COOR, ( HO. and—COR), and R is C1 -C6 linear or branched alkyl (e.g. , C 1-C6, C1-C5, C 1-C4, C1-C3, C I - C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
[123] In some of the variations of formula (4a), k is 2- 10, each Ra and Rb is II, and R} to ^ are as described above for formula (4). In some of these variations, k is 6 or 8, each Ra and ϊ¾> is H, and each of j to R<, independently is absent or is a halo. In particular variations, k is 6 or 8, each Ra and ¾ is H, and Ri to Re are all absent.
[124] In some of the variations of formula (4a), k is 2-10, Ra and Rb are either H or
Figure imgf000047_0001
, and i to c, are as described above for formula (4). In some of these variations, k is 6 or 8, Ra and
Rb are either H or "^- and each of Ri to R¾ independently is absent or is a halo. In particular ariations, k is 6 or 8, Ra and Rj, are either H or
Figure imgf000047_0002
and j to ¾ are all absent.
O
[125] In some of the variations of tormula (a4), k is 2- 10, Ra and j, are either H or "¾ , and i to ¾ are as described above for formula (4). In some of these variations, A is 6 or 8, Ra and
O
Rj, are either H or '¾ and each of Ri to f, independently is absent or is a halo. In particular
O
variations, k is 6 or 8, Ra and Rj, are either H or '¾ and Rs to R6 are all absent.
[126] In some of the variations of formula (4a), k is 2- 10, each Ra and R¾ is H or two of CRaRb are ^ and i to e are as described above for formula (4). In some of these variations, k is
6 or 8, each Ra and Rb is H or two of CRa¾ are ' L , and each of Ri to ¾ independently is absent or is a halo. In particular variations, k is 6 or 8, each Ra and Rj, is H or two of CRaRb are
' L and Ri to s are all absent. [127] One of skill in the art can readily visualize and prepare other cationic mul timers falling within formula (4) in which other cationic dye moieties are used in place of one or both of the safranin-0 moieties.
Some cationic dye dimers fall within formula (5):
Figure imgf000048_0001
, wherein each of Dl and D2 is a cationic dye moiety, n is 0-6, and nj is 1-4.
[129] In some variations of formula (5), Dl and D2 are different cationic dye moieties. In other variations of formula (5), Dl and D2 are the same cationic dye moiety. In some variations of formula (5), Dl and D2 are independently selected from the group consisting of safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue.
[130] In some variations of formula (5) described in the paragraphs above, n is 0-6, 0-5, 0-4, 0- 3, 0-2, 0-1, 1-6, 1-5, 1-4, 1-3, 1-2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, 5-6, 0, I, 2, 3, 4, 5, or 6.
[131] In some variations of formula (5) described in the paragraphs above, n} is 1-4, 1-3, 1-2, 2-4, 2-3, 3-4, 1 , 2, 3, or 4,
[132] In some variations of formula (5) described in the paragraphs above, Dl is safranin-O. In some vaiiations of formula (5) described in the paragraphs above, D2 is safranin-O. In some variations of formula (5) described in the paragraphs above, Dl and D2 are safranin-O.
[133] In some variations of formula (5) described in the paragraph above, the pendant phenyl ring of Dl is unsubstituted. In some variations of formula (5) described in the paragraph above, the pendant phenyl ring of Dl is substituted with 1-3 (e.g., 1-3, 1-2, 1, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of Dl is substituted, the
substituents are selected independently from— -NH2,— NHR,— NR2,— OH,— O",
— NHCOCH3, --NHCOR, --OCH3,—OR, --C2H5,—R, and C,,l k wherein R is C1-C6 linear or branched alky! (e.g., C1-C6, C 1-C5, C1-C4, C 1-C3, C1-C2, C I , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— 02,— NR3 , halo (e.g., F, Br, CI, I), trihaiide (e.g.,— CF3,— CC13,— CBr3, (' ! : )..— CN,— S03H,— COOH,— COOR,— CIIO, and — COR, wherein R is C1-C6 linear or branched alkyl (e.g., C 1 -C6, C 1-C5, C1 -C4, C 1-C3, C l- C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched aikyi ).
[134] In some variations of formula (5) described in the paragraph above, the pendant phenyl ring of 1)2 is unsubstituted. In some variations of formula (5) described in the paragraph above, the pendant phenyl ring of D2 is substituted with 1-3 (e.g., 1-3, 1-2, 1, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position 011 the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— -NH2,— NHR,— NR2,— OH,— O",
— NHCOCH3, -- HCOR, --OCH3,—OR, --C2H5,—R, and C,,l k wherein R is C1-C6 linear or branched alkyl (e.g., C1-C6, C 1-C5, C1-C4, C 1-C3, C1-C2, C I , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— -N02,— -NR3 +, halo (e.g., F, Br, CI, I), trihaiide (e.g.,— CF3,— CCI3,— CBr3,— CI3),— CN,— SO3H, -—COOH, -—COOR,— CHO, and — COR, wherein R is C1.-C6 linear or branched al kyl (e.g., C 1 -C6, C1-C5, C 1 -C4, C 1 -C3, C l- C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
[135] Some cationic dye dimers fall within formula (6):
Figure imgf000049_0001
, wherein each of Dl and D2 is a cationic dye moiety, fir is 0-5, and n2 is 1-5.
[136] In some variations of formula (6), Dl and D2 are different cationic dye moieties. In other variations of formula (6), Dl and D2 are the same cationic dye moiety. In some variations of formula (6), Dl and D2 are independently selected from the group consisting of safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue. [137] In some variations of formula (6) described in the paragraphs above, n} is 0-5, 0-4, 0-3,
0- 2, 0-1, 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1, 2, 3, 4, or 5.
[138] In some variati ons of formula (6) described in the paragraphs above, n2 is 1 -5, 1-4, 1-3,
1- 2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5.
[139] In some variati ons of formula (6) described in the paragraphs above, Dl is safranin-O. In some variations of formula (6) described in the paragraphs above, D2 is safranin-O. In some variations of formula (6) described in the paragraphs above, Dl and D2 are safranin-O.
[140] In some variations of formula (6) described in the paragraph above, the pendant phenyl ring of Dl is unsubstituted. In some variations of formula (6) described in the paragraph above, the pendant phenyl ring of Dl is substituted with 1-3 (e.g., 1 -3, 1-2, 1 , 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— -NH2,— NHR,— NR2,— OH,— O",
— ICOCH3, XI li OR. (X I k—OR,— C2H5,— R, and G,! k wherein R is C1-C6 linear or branched alkyl (e.g., C1-C6, C1-C5, C1-C4, C 1-C3, C1-C2, CI , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— O?,— NR3 , halo (e.g., F, Br, CI, I), trihaiide (e.g.,— CF3, --CCI3, ---CBr3, --CI3),— CN, SO;! !, --COOH, --COOR, --CHO, and — COR, wherein R is C1-C6 linear or branched alkyl (e.g., C 1-C6, C1-C5, C1-C4, C 1-C3, Cl- C2, CI , C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
[141] In some variati ons of formula (6) described in the paragraph above, the pendant phenyl ring of D2 is unsubstituted. In some variations of formula (6) described in the paragraph above, the pendant phenyl ring of D2 is substituted with 1-3 (e.g., 1-3, 1-2, 1, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— -NH2,— NHR,— NR2,— OH,— O",
— NHCOCH3,— NHCOR,— OCH3,—OR,— C2H5,— R, and— C6¾, wherein R is C1-C6 linear or branched alkyl (e.g., C1-C6, C1-C5, C1-C4, C1-C3, C1-C2, CI , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl ). In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— -N02,— -N 3 +, halo (e.g., F, Br, CI, I), trihalide (e.g.,— CF3,— CC13,— CBr3,— CI3),— CN,— SO3H,— COOH,— COOR,— CHO, and — COR, wherein R is C1-C6 linear or branched alkyl (e.g., C1-C6, C1-C5, C1-C4, C1-C3, Cl- C2, CI, ( '2 ·(·(>, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-
(26, C5, or C6 linear or branched alkyl),
[142] Some cationic dye dimers fall within formula (7):
Figure imgf000051_0001
(7) , in which each of Dl and D2 is a cationic dye moiety,
Uj is 0-5, and « is 1-5
[143] In some variations of formula (7), Dl and D2 are different cationic dye moieties. In other variations of formula (7), Dl and D2 are the same cationic dye moiety. In some variations of formula (7), Dl and D2 are independently selected from the group consisting of safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue.
[144] In some variations of formula (7) described in the paragraphs above, tj is 0-5, 0-4, 0-3,
0- 2, 0-1 , 1 -5, 1-4, 1 -3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1 , 2, 3, 4, or 5,
[145] In some variations of formula (7) described in the paragraphs above, n2 is 1-5, 1-4, 1-3,
1 - 2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5.
[146] In some variations of formula (7) described in the paragraphs above, Dl is safranin-O. In some variations of formula (7) described in the paragraphs above, D2 is safranin-O. In some variations of formula (7) described in the paragraphs above, Dl and D2 are safranin-O.
[147] In some variations of formula (7) described in the paragraph above, the pendant phenyl ring of Dl is un substituted. In some variations of formula (7) described in the paragraph above, the pendant phenyl ring of Dl is substituted with 1-3 (e.g., 1-3, 1-2, I, 2, or 3) electron-donating or electro -with drawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— NH2,— -NHR,— NR2,— OH,— O", --NHCOCH3,— -NHCOR, --OCH3,—OR, --C2H5, R, and— C6H5, wherein R is C1-C6 linear or branched alkyl (e.g., C1-C6, C 1-C5, C1-C4, C1-C3, C1-C2, CI, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— N02,— NR3 +, halo (e.g., F, Br, CI, I), trihalide (e.g.,— CF3, CCk— CBr3,—CI3),— CN,— S03H, COOH,— COOR,—CHO, and — COR, wherein R is C1-C6 linear or branched alkyl (e.g., C1-C6, C1-C5, C1-C4, C 1-C3, Cl- C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
[148] In some variations of formula (7) described in the paragraph above, the pendant phenyl ring of D2 is unsubstituted. In some variations of formula (7) described in the paragraph above, the pendant phenyl ring of 1)2 is substituted with 1-3 (e.g., 1-3, 1 -2, 1, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— NH2,— -NHR,— -NR2,— OH,— O",
— NHCOCH3,— HCOR, GO I :.— OR,— C2¾,— , and— C6H5, wherein R is C1-C6 linear or branched alkyl (e.g., C1 -C6, C 1 -C5, C1 -C4, C1 -C3, C1-C2, CI, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— N02,— NR3 +, halo (e.g., F, Br, CI, I), trihalide (e.g.,— CF3, --CCI3, --CBr3, --CI3),— CN, SO I i, COOH, COOR. CI 10, and —COR, wherein R is C1-C6 linear or branched alkyl (e.g., C1-C6, C1-C5, C1-C4, C1-C3, Cl - C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
Some cationic dye dimers fall within formula (8):
Figure imgf000052_0001
(8) , in which each of Dl and D2 is a cationic dye moiety, n} is 0-5, and n2 is 1-5. [150] In some variations of formula (8), Dl and D2 are different cationic dye moieties. In other variations of formula (8), Dl and D2 are the same cationic dye moiety. In some variations of fomiula (8), Dl and D2 are independently selected from the group consisting of safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue.
[151] In some variations of formula (8) described in the paragraphs above, n} is 0-5, 0-4, 0-3,
0- 2, 0-1, 1-5, 1 -4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1, 2, 3, 4, or 5.
[152] In some variations of formula (8) described in the paragraphs above, n2 is 1 -5, 1-4, 1-3,
1- 2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1 , 2, 3, 4, or 5,
[153] In some variations of formula (8) described in the paragraphs above, Dl is safranin-O. In some variations of formula (8) described in the paragraphs above, D2 is safranin-O. In some variations of formula (8) described in the paragraphs above, Dl and D2 are safranin-O.
[154] In some variations of formula (8) described in the paragraph above, the pendant phenyl ring of Dl is unsubstituted. In some variations of formula (8) described in the paragraph above, the pendant phenyl ring of Dl is substituted with 1-3 {e.g., 1-3, 1-2, 1, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— M k— NHR,— NR2,— OH,— O",
— NHCOCH3,— HCOR,— OCH3,—OR,— C2H5,— R, and— C6¾, wherein R is C1-C6 linear or branched alky! {e.g., C1-C6, C1-C5, C1-C4, C1-C3, C1-C2, CI , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— -NO2,— - R3 +, halo {e.g., F, Br, CI, I), trihalide {e.g.,— CF3,— CCI3,— CBr3, ( O..— CN, SO: I f .— COOH,— COOR,— CIIO, and — COR, wherein R is C1-C6 linear or branched alkyl {e.g., C1-C6, C1-C5, C1-C4, C 1-C3, Cl- C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
[155] In some variations of formula (8) described in the paragraph above, the pendant phenyl ring of 1)2 is unsubstituted. In some variations of formula (8) described in the paragraph above, the pendant phenyl ring of D2 is substituted with 1-3 {e.g., 1-3, 1-2, I, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— -NH2,— NHR,— NR2,— OH,— O", — NHCOCH3,— -NHCOR, --OCH3,—OR, --C2H5, R, and --C6H5, wherein R is C1-C6 linear or branched aikyi (e.g., C1-C6, C 1-C5, C1-C4, C 1-C3, C 1-C2, C I, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched aikyi). In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— N02,— R3 +, halo (e.g., F, Br, CI, I), trihalide (e.g., ---CF3, CCk --CBr3,—CI3),— CN, - -SO3H,—COOH,— COOR,—CHO, and — COR, wherein R is C1-C6 linear or branched aikyi (e.g., C 1-C6, C1-C5, C1-C4, C 1-C3, Cl- C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched aikyi).
[156] Some cationic dye dimers fall within formula (9):
Figure imgf000054_0001
(9) , in which each of Dl and D2 is a cationic dye moiety and
«/ and n2 independently are 1-5.
[157] In some variations of formula (9), Dl and D2 are different cationic dye moieties. In other variations of formula (9), Dl and D2 are the same cationic dye moiety. In some variations of formula (9), Dl and D2 are independently selected from the group consi sting of safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue.
[158] In some variations of formula (9) described in the paragraphs above, rij is 1-5, 1 -4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, I , 2, 3, 4, or 5.
[159] In some variations of formula (9) described in the paragraphs above, «2 is 1-5, 1 -4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, I , 2, 3, 4, or 5.
[160] In some variations of formula (9) described in the paragraphs above, Dl is safranin-O. In some variations of formula (9) described in the paragraphs above, D2 is safranin-O. In some variations of formula (9) described in the paragraphs above, Dl and D2 are safranin-O.
[161] In some variations of formula (9) described in the paragraph above, the pendant phenyl ring of Dl is unsubstituted. In some variations of formula (9) described in the paragraph above, the pendant phenyl ring of Dl is substituted with 1-3 (e.g., 1-3, 1 -2, 1, 2, or 3) electron-donating or electro -with drawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— NH2,— NHR,— NR2,— OH,— O",
— - HCOCH3,—NHCOR, --OCH3, OR, C -Ι !·:,— R, and ---C6H5, wherein R is C1-C6 linear or branched alkyl (e.g., C 1 -C6, C 1 -C5, C 1-C4, C 1 -C3, C 1-C2, CI, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— N02,— 'NR3 T, halo (e.g., F, Br, CI, I), trihalide (e.g. ,— CF-i, ~~CCU,— CBr3,— CI3),— CN,— S03H,— COOH,— COOR,— CHO, and —COR, wherein R is C1 -C6 linear or branched alkyl (e.g., C 1-C6, C1 -C5, C1-C4, C 1-C3, Cl - C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
[162] In some variations of formula (9) described in the paragraph above, the pendant phenyl ring of D2 is unsubstituted. In some variations of formula (9) described in the paragraph above, the pendant phenyl ring of D2 is substituted with 1-3 (e.g., 1 -3, 1-2, 1 , 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— NH?,— NHR,— NR2,— OH,— O",
— -NHCOCH3,— HCOR, --OCH3, OR, --C2H5,— R, and O.l k wherein R is C1 -C6 linear or branched alkyl (e.g., C 1-C6, C 1-C5, C 1-C4, C 1-C3, C 1-C2, CI, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— 02,— R3 1, halo (e.g., F, Br, CI, I), trihalide (e.g. , --CF3, --CCI3, ---CBi-3, --CI3),— CN, --SO3H, COOH, COOR, --CHO, and — COR, wherein R is C 1-C6 linear or branched alkyl (e.g., C 1-C6, C 1-C5, C1-C4, C 1-C3, C l - C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl). 63] Some cationic dye mul timers fall within formula (10):
Figure imgf000056_0001
(10) . wherein each of Dl and D2 is a cationic dye moiety and n is 1-6,
[164] In some variations of formula (10), Dl and D2 are different cationic dye moieties. In some variations of formula (10), Dl and D2 are the same cationic dye moiety. In some variations of formula (10), Dl and D2 independently are selected from the group consisting of safranin-O, toiuidine blue, azure A, azure B, azure C, acridine orange, acrifiavine, and methylene blue.
[165] In some variations of formula (32) described above, n is 1 -6, 1-5, 1 -4, 1-3, 1-2, 2-6, 2-5, 12-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, 5-6, 1, 2, 3, 4, 5, or 6,
[166] In some variations of formula (10) described in the paragraphs above, Dl is safranin-O. In some variations of formula (10) described in the paragraphs above, D2 is safranin-O. In some variations of formula ( 10) described in the paragraphs above, Dl and D2 are safranin-O.
[167] In some variations of formula (10) described in the paragraph above, the pendant phenyl ring of Dl is unsubstituted. In some variations of formula (10) described in the paragraph above, the pendant phenyl ring of Dl is substituted with 1-3 (e.g., 1-3, 1-2, 1, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of Dl is substituted, the
substituents are selected independently from— NH2,— NHR,— NR2,— OH,— O",
— NHCOCH3, --NHCOR, --OCH3,—OR, --C2H5,—R, and C,,l k wherein R is C1-C6 linear or branched alky! (e.g., C 1-C6, C 1-C5, C1-C4, C 1-C3, C1-C2, C I , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched aikyi). In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— -N02,— -N 3 +, halo (e.g., F, Br, CI, I), trihalide (e.g.,— CF3,— CCI3,— CBr3,— CI3),— CN,— SO3H,— COOH,— COOR,— CHO, and — COR, wherein R is C1-C6 linear or branched al ky] (e.g., C 1 -C6, C1-C5, C 1 -C4, C 1 -C3, C l- C2, CI , C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-
C6, C5, or C6 linear or branched alkyl).
[1 8] In some variations of formula (10) described in the paragraph above, the pendant phenyl ring of D2 is unsubstituted. In some variations of formula (10) described in the paragraph above, the pendant phenyl ring of D2 is substituted with 1-3 (e.g., 1 -3, 1-2, 1 , 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of D2 is substituted, the
substituents are selected independently from— -NH2,— NHR,— NR2,— OH,— O",
— NHCOCH3,— NHCOR,— OCH3,—OR,— C2H5,— R, and— C6¾, wherein R is C 1-C6 linear or branched alkyl (e.g., C 1-C6, C 1-C5, C1-C4, C 1-C3, C1-C2, CI , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl ). In some embodiments in which the pendant phenyl ring of 1)2 is substituted, the substituents are selected independently from— -NO2,— -NR3 +, halo (e.g., F, Br, CI, I), trihalide (e.g. ,— CF3,— CCI3,— CBr3,— CI3),— CN,— S03H,— COOH,— COOR,— CHO, and — COR, wherein R is C1-C6 linear or branched alkyl (e.g., C 1 -C6, C 1-C5, C1 -C4, C 1-C3, C l- C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
[169] In some of the variations of formula (10) described above, Dl and D2 are safranin-0 moieties, as shown in formula (10a):
Figure imgf000057_0001
in which n is 1 -6, Rj, R2, R3, R4, R5, and R independently are absent or independently are selected from \i k—NHR,— NR2,—OH,— O",— NHCOCH3,— NHCOR,— OCH3,—OR,
--C2H5, --R,--C6H5, NO ,— NR3 +, halo (e.g., F, Br, CI, I), trihalide (e.g., --CF3, --CCI3, — CBr3,— CI3),— CN,— SO3H,—COOH,—COOR,—CHO, and—COR), and R is C 1-C6 linear or branched alkyl (e.g., C1 -C6, C 1 -C5, C1 -C4, C 1 -C3, C1 -C2, C I, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl).
[170] In some variations of formula (10a), n is 1-6, 1-5, 1-4, 1-3, 1-2, 2-6, 2-5, 2-4, 2-3, 3-6, 3- 5, 3-4, 4-6, 4-5, 5-6, 1, 2, 3, 4, 5, or 6.
[171] One of skill in the art can readily visualize and prepare other cationic multimers falling within formula ( 10) in which other cationic dye moieties are used in place of one or both of the safranin-0 moieties.
[172] Some cationic dye dimers fall within formula (1 1 ):
Figure imgf000058_0001
^ I , in which each of Dl and D2 is a cationic dye moiety; lj and
I2 independently are 1-4; n is 1-4; ring A is aryl, heteroaryl, cycloalkyl, or heterocyclyl; for each independent instance of ai and J¾(i, Rai and ¾i (1) independently are H or CH3, or (2) Ral and ibi are
Figure imgf000058_0002
or or (3) two of CRaiRbi are ; and, for each independ instance of R¾2 and Rb2, a2 and R 2 (1 ) independently are H or CH3, or (2) Ra2 and R¾2 are
Figure imgf000058_0003
or
Figure imgf000058_0004
or (3) two of C a2R!)2 are
[173] In some variations of formula (1 1 ), Dl and D2 are different catiomc dye moieties. In other variations of formula (1 1), Dl and D2 are the same cationic dye moiety. In some variations of formula (1 1 ), Dl and D2 are independently selected from the group consisting of safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue.
[174] In some variations of formula (1 1), h is 1-4, 1-3, 1-2, 2-4, 2-3, 3-4, l , 2, 3, or 4.
[175] In some variations of formula (1 1) described in the paragraphs above, L is 1 -4, 1-3, 1-2, 2-4, 2-3, 3-4, 1 , 2, 3, or 4, [176] In some variations of formula (1 ) described in the paragraphs above in which l} is 1 , Rai and ¾ί are both H. In some variations of formula (1 1) described in the paragraphs above in which lj is 1 , Rai is H and R¾i is CH3. In some variations of formula (1 1 ) described in the paragraphs above in which h is 1 , ai and Rbi are both CH3. In some variations of formula (1 1) described in the paragraphs above in which 1} is 1, Rai and i are "¾ . In some variations of
O
formula (1 1) described in the paragraphs above in which h is I, Rai and &j are ^\
[177] In variations of formula (1 1 ) described in the paragraphs above in which is 2, the two instances of Ra and Rj, are indicated as ai and i and Ra2 and Rb2, respectively. In some variations of formula (1 1 ) described in the paragraphs above in which i s 2, each of Rai and Rbi and Ra2 and 2 is H. In some variations of formula (1 1) described in the paragraphs above in which lj is 2, each of Rai and Rbi and ^ and j,2 is CH3. In some variations of formula (1 ) described in the paragraphs above in which is 2, each of Rai and Ra2 is H and each of Rbi and Rs,2 is CH3. In some variations of formula (1 1) described in the paragraphs above in which l} is 2, each of Rai, Ra2, and Rbi is H and ¾2 is CH3.
[178] In some variati ons of formul a (1 1) described in the paragraphs above in which lj is 2, each of Ra{ and R i is H and Ra2 and ¾2 are '¾ . In some variations of formula (1 1)
described in the paragraphs above in which i} is 2, each of Rai and Rbi is H and ^ and Rj,2 are O
'¾· . In some variations of formula (1 1) described in the paragraphs above in which l} is 2, each of ai and M is CH3 and Ra2 and b2 are '¾ . In some variations of formula (1 1) described in the paragraphs above in which lj is 2, each of Rai and R1(i is CH3 and Ra2 and ¾2 O
are
In some variations of formula (1 1) described in the paragraphs above in which I} i s 2, Ra3 is H, bi is CH3, and Ra2 and 2 are '¾¾ . In some variations of formula (1 1) described in the
O
paragraphs above in which ¾ is 2, Rai is H, i is CH3, and Ra2 and ¾2 are ' <- . In some variations of formula (1 1) described in the paragraphs above in which h is 2, Ra! and ¾i and RA2 and R¾2 together are ' ¾ . In some variations of formula (1 1) described in the paragraphs above in which ; is 2, Rai and ¾i are '^- ** ¾ and ¾2 are '^- . In some variations of formula 1 1) described in the paragraphs above in which l} is 2, Ral and Rbi are ^ Ra2 and
Rb2 are
Figure imgf000060_0001
In some variations of formula (1 1 ) described in the paragraphs above in which
O O
is 2, Ral and Rbi are Ra2 and b2 are ^\
[179] In variations of formula (1 1 ) described in the paragraphs above in which l} is 3, the three instances of Ra and Rb are indicated as ai and bi; Ra2 and Rb2; and Ra3 and ¾. respectively. In some variations of formula (1 1) described in the paragraphs above in which is 3, In some variations of formula ( 1 1 ) described in the paragraphs above in which l} is 3, each of Rai,Rbi, Ra2, R¾2, a3, and Rbs is H. In some variations of formula (1 1) described in the paragraphs above in which Ij is 3, each of Rai,Rbi, Ra2, ¾2, Ras, and
Figure imgf000060_0002
is CH3. In some variations of formula (1 1) described in the paragraphs above in which is 3, each of Rai,Rbj, Ra2, and Rb2, is H and each of Ra3 and R^ i s CH3. In some variations of formula ( 1 1 ) described in the paragraphs above in which / is 3, each of Rai,Rbi, a2, and ¾2, is CH3 and each of Ra3 and Rj,3 is H. In some variations of formula (1 1) described in the paragraphs above in which Ij is 3, Rai is H and each of Ra2, A3. Rbi, Rb2, and Rb3 is CH3. In some variations of formula (1 1) described in the paragraphs above in which !} is 3, each of Rai and Ra2 is H and each of Raj, Rbi, ¾2, and R¾3 is CH3. In some variations of formula (1 1) described in the paragraphs above in which l} is 3, each of Rai, Ra2, and 33 is H and each of Rbi, RM, and bs s (Ί \ .
[180] In some variations of formula (1 1) described in the paragraphs above in which Ij is 3, each of Rai,Rbi, a2, and Rb2, is H and
Figure imgf000060_0003
. In some variations of formula (1 1) described in the paragraphs above in which is 3, each of Rai,Rbi, RA2, and Rb2, is CH3 and A3 and Rb3 are " . In some variations of formula (1 1) described in the paragraphs above in which li is 3, Rai is H and each of Ra2, Rbi , and Rb2 is CH3, and Ra3 and Rb3 are "^- . in some variations of formula (1 1 ) described in the paragraphs above in which i s 3, each of Rai and Ra2 is H and each of Rbi and R1(2 is CH3, and 33 and s are
Figure imgf000060_0004
[181] In some variations of formula (1 1) described in the paragraphs above in which l} is 3,
O
each of Rai,Rw, Ra2, and ¾>2, is H and Ra3 and 1¾3 are ^\ In some variations of formula (1 1) described in the paragraphs above in which lj is 3, each of Rai,¾i, Ra2, and ¾2, is CH3 and a3
O
and Rj,3 are '^- In some variations of formula (1 1 ) described in the paragraphs above in which
O
/ is 3, Rai is H and each of Ra2, Rbj, and i,2 is CH3, and R^ and Rj,3 are ^\ In some variations of formula (1 1) described in the paragraphs above in which lj is 3, each of Rai and Ra2
O
is H and each of Rbi and ¾2 is CH3, and Ras and R¾3 are
[182] In some variations of formu 1 described in the paragraphs above in which / is 3, ai and RM a , and each of and ¾3 is H. In some variations ot formula (
Figure imgf000061_0001
1 1) described in the paragraphs above in which lj is 3, Ra! and ¾i are 2 and
Rj,2 re '¾ , and each of Ra3 and ^s i CH3. In some variations ot formula (1 1 ) described in the paragraphs above in which lj_ is 3, RaJ and Rbi are '¾ Ra2 and Rb2 are '¾ ^ is H, and Rb3 i s CH3. In some variations of formula (1 1) described in the paragraphs above in which
Figure imgf000061_0002
, Ra2 and Rj,2 are , and each of as and Rb3 is H. In some
ribed in the paragraphs above in which h is 3, Rai and Rbi are
Figure imgf000061_0003
ancf each of Ra3 an(j Rb3 is en . In some variations of formula
(1 1) described in the paragraphs above in which l} is 3, Rai and Rbi are '¾ Ra2 and Rb2 are
Figure imgf000061_0004
[183] In some variations of formula (1 1) described in the paragraphs above in which / is 3, ai
*r O
and R i are Ra2 and ¾2 are , and each of R^ and Rb3 is H. In some variations of formula (1 1 ) descri bed in the paragraphs above in which i s 3, Rai and Rbi are '¾· Ra2 and O
¾2 are ' *· and each of Ra3 and 3 is CH3. In some variations of formula (11) described in
O
the paragraphs above in which lj is 3, ai and ¾i are "¾ A2 and ¾2 are A3 is H, and Rb3 is CH3. In some variations of formula (11) described in the paragraphs above in which l}
O
is 3, Rai and R¾i are "¾ Ra2 and Rj,2are '¾· and each of A3 and ^is H. In some variations of formula (11) described in the paragraphs above in which ; is 3, Rai and RM are
O
'¾ Ra2 and R^are f\ and each of RA3 and s^i CH3. In some variations of formula
(11) described in the paragraphs above in which l} is 3, Rai and i are '¾ , RA2 and ¾2 are O
-\ Ra3 is H, and Rb3 is CH3.
[184] In some variations of formula (11) described in the paragraphs above in which / is 3, Rai
O O
and Rj,i are Ra2 and Rb2are *¾ and each of Ras and b3is H. In some variations of
O
formula (11) described in the paragraphs above in which ; is 3, ai and M are · Ra2 and
O
j)2 are f\ and each of aj and ¾3 is CH3. In some variations of formula (11) described in
O O
the paragraphs above in which is 3, RAI and Rt>i are , RA2 and ¾2 are · A is H, and b3¾ s CH3. In some variations of formula (11) described in the paragraphs above in which lj is 3, ai and Rbi are
Figure imgf000062_0001
and each of as and bsis H. In some variations of formula (11) described in the paragraphs above in which l} is 3, aj and R^ are O O
' <* a2 and Rb2 are '¾· and each of aj and Rb3 is CH3. In some variations of formula (11)
o o described in the paragraphs above in which lj is 3, Rai and bi are "*· Ra2 and 2 are ·
Figure imgf000062_0002
[185] In some variations of formula (11) described in the paragraphs above in which l} is 3, Ral and ¾i and RA2 and j,2 together are " and each of aa and Rj>3 is H. In some variations of formula (1 1) described in the paragraphs above in which i} is 3, RaJ and Rh{ and Ra2 and ^ together are ' x, and each of RA3 and bs is CH3. In some variations of formula (11) described in the paragraphs above in which / is 3, Ra5 and M and Ra2 and s,2 together are )■ (
' L , Ra3 is H, and t,3 is CH3. In some variations of formula (1 1) described in the paragraphs above in which lj is 3, Rai and Rj,i and R^ and Κ¾2 together are 'x and RA3 and ¾3 are
In some variations of formula (1 1) described in the paragraphs above in which l} is 3, RaX
O
and Rbi and Ra2 and Rj>2 together are ""v a anndd R„a3¾ anηάd ¾3 are
[186] In vari ations of formula (11) described in the paragraphs above in which // is 4, the three instances of Ra and j, are indicated as Rai and Rbi; Ra2 and Rj,2; A3 and j,3; and A4 and ¾4, respectively. In some variations of formula (11) described in the paragraphs above in which / is 4, In some variations of formula (11) described in the paragraphs above in which l} is 4, each of Rai,R¾i, Ra2, Rb2, ¾3, ¾3. RA4, and R& is H. In some variations of formula (11) described in the paragraphs above in which lj is 4, each of Rai,Rt>i, ¾2, 2, a3, 3, A , and ¾4 is CH3. In some variations of formula (11) described in the paragraphs above in which // is 4, each of Rai, Ra2, i>2, a3, a d R^ is H and each of RA4 and ^ is CH3. In some variations of formula (1 1) described in the paragraphs above in which !} is 4, each of Rai, ¾i, Ra2, and Rj,2 is H and each of Ra3, Rj>3. RA4, and R^ is CH3. In some variations of formula (1 1) described in the paragraphs above in which i} is 4, each of Rai, Ra2, Rb2, a3, and ^ is CH3 and each of RA4
Figure imgf000063_0001
[187] In some variations of formula (11) described in the paragraphs above in which l} is 4, each of Ra{,Ra2, and Ra3 is II and each of RM, (,2, and j,3 is CH3. In some variations of formula (11) described in the paragraphs above in which lj is 4, Rai is H, *i is CH3, and each of Ra2, ¾2, a3, and j,3 is CH3. In some variations of formula (11) described in the paragraphs above in which is 4, Rai is H, R¾i is CH3, and each of R^, M, A3, and R 3 is H. In some variations of formula (11) described in the paragraphs above in which ; is 4, each of Rai and Ra2 is H, each of M and j,2 is CH3, and each of Ra3 and !½ is H. In some variations of formula (11) described in the paragraphs above in which is 4, each of Rai and Ra2 is H, each of RM and Rb2 is (Ί f and each of Ra3 and ¾3 is CH3. [188] In some variations of formula (1 ) described in the paragraphs above in which l} is 4, Rai
Figure imgf000064_0001
and ¾ι are H, are . In some variations of formula (11) described in the paragraphs above in which i} is 4, Ra! and &j are H,
Ra2 and Rb2 are H, Ra3 and Rb3 are CH3, and Ra4 and R 4 are '¾ . In some variations of formula (11) described in the paragraphs above in whic !} is 4, Rai and ¾ι are H, R^ and ¾2 are CII3, ¾ and ¾3 are CH3, and RA4 and ¾4 are '¾ , In some variations of formula (11) described in the paragraphs above in which is 4, Rai and bi are CH3, Ra2 and Rb2 are CH3,
Ra3 and B3 are CH3, and Ra4 and R¾4 are "¾ <^ .
[189] In some variations of formula (1 1) described in the paragraphs above i which is 4, Raj
Figure imgf000064_0002
and jji are H, Ra2 and Rb2 are H, Ra3 and ¾3 are "^- and Ra4 and Rb are . In some variations of formula (1 1 ) described in the paragraphs above in which lj is 4, Rai and RM are H,
Ra2 and R 2 are CH3, A3 and *»3 are
Figure imgf000064_0003
, In some variations of formula (11) described in the paragraphs above in which i} is 4, Ra! and &j are CH3, Ra2 and
Rb2 are CH3, R^ and Rb3 are "^- , and Ra4 and R 4 are "¾ . In some variations of formula (11) described in the paragraphs above in which l} is 4, Ral is H, R¾i is CH3, Ra2 and R 2 are
CH , Ra3 and ¾>3 are L and Ra4 and R¾4 are '¾ . In some variations of formula (1 1) described in is H, Rb2 is CH3, A3
Figure imgf000064_0004
and Rb3 are , and Ra4 a d R¾4 are ^ .
] In some variations of formula (1 1) described in the paragraphs above in which is 4, RaJ and bi are H, Ra2 and Rb2 are *" , Ra3 and &3 are
Figure imgf000064_0005
In some variations of formula (1 1) described in the paragraphs above in which !} is 4, Ral and Rbl are CH3, R^ and R 2 are "*· aj and Rt,3 are "¾ ^", and Ra4 and RM are '¾ ^ . In some variations of formula (11) described in the paragraphs above in which i} is 4, Ra! is H, Rbi is a2 and ¾2 are "¾ ^\ as and B are "^- and Ra4 and Rb4 are . In some variations of formula (11) described in the paragraphs above in which ¾ is 4, ai and R i are
Figure imgf000065_0001
[191] In some variations of formula (11) described in the paragraphs above in which l} is 4, Rai
9
and RM are H, Ra2 and ¾2 are H, Ra3 and R&j are II, and RA4 and RM are '*> ^ . In some variations of formula (11) described in the paragraphs above in which I} is 4, Ral and RM are H,
O
Ra2 and Rb2 are H, Ra3 and (,3 are CH3, and A4 and KM are . In some variations of formula (11) described in the paragraphs above in which is 4, ai and R i are H, ^ and 2
O
are CH3, A3 and 3 are CH3, and A4 and ¾4 are ^\ In some variations of formula (11) described in the paragraphs above in which lj is 4, Rai and ¾i are CH3, Ra2 and R¾2 are CH3,
O
Ra3 and Rb5 are CH3, and Ra4 and M are "^- .
[192] In some variations of formula (11) described in the paragraphs above in which l} is 4, RaJ
O
and Rbi are H, R^ and ϊ¾>2 are H, Ra3 and 3 are '¾· ^\ and Ra and R\v% are v. In some variations of formula (11) described in the paragraphs above in which ; is 4, ai and ¾i are H,
2 and Rb2 are CH3, Ra3 and s are
Figure imgf000065_0002
In some variations of formula (11) described in the paragraphs above in which is 4, ai and bi are CH3, Ra2 and
O o
are CH3, RA3 and R¾3 are *" , and A4 and M are '¾· , In some variations of formula
(11) described in the paragraphs above in which Ij is 4, Rai is H, ¾i is CH3, Ra2 and Rj,2 are
A A CH3, Ra3 and ¾>3 are and Ra4 and 4 are In some variations of formula (11) described in the paragraphs above in which is 4, Rai is H, R¾i is CH3, R^ is H, ¾2 is CH3, A3 and ba are
Figure imgf000065_0003
[193] In some variations of formula (11) described in the paragraphs above in which l} is 4, Rai and ¾i
Figure imgf000066_0001
variations of formula (11) described in the paragraphs above in which h i s 4, Rai and R¾i are
0 0 o
CH3, Ra2 and R¾,2 are ^ Ra3 and Rb3 are ^ ^· *, and Ra4 and RM are ^ ^- . In some variations of formula (11) described in the paragraphs above in which lj is 4, Ra! is H, Rh{ is
CH3, Ra2 and Rj,2 are
Figure imgf000066_0002
In some variations
O
of formula (11) described in the paragraphs above in which lj is 4, ai and ¾i are ·· Ra2 and Ri»2 are
Figure imgf000066_0003
[194] In some variations of formula (11) described in the paragraphs above in which lj is 4, Rai and Rbi are "¾ , Ra2 and b2 are H, Ra3 and R¾ are H, and Ra4 and R¾4 are '¾· . In some variations of formula (11) described in the paragraphs above in which lj is 4, Rai and R¾i are
O
and Rb2 are CH3, Ra3 and Rb3 are CH3. and Ra4 and M are '¾A ^ . In some variations of formula (11) described in the paragraphs above in which lj is 4, Rai and Ι¾ί are '¾ ^* , Ra2
O
and i,2 are H, 33 and b3 are CH3, and Ra4 and R¾4 are · 5 ,
[195] In some variations of formula (11) described in the paragraphs above in which l} is 4, Rai
O
and Rbi are '¾ , Ra2 and Rj,2 are '¾ , Ra and R¾ are H, and Ra4 and R¾4 are . In some variations of formula (1 1) described in the paragraphs above in which is 4, Rai and Rbi
Figure imgf000066_0004
are . In some variations of formula (1 1) described in the paragraphs above in which is 4, ai and R i are
< - 5 RA2 ancj RB2 ARE 'T ^ - 3 R R„A3! a annd(j ] R¾..3! a ArReE Γ CΉH-3, a anndd R R„A4< a anndd R I¾k>,. a arree " '¾¾·· ^ ^ . In some variations of formula (1 1 ) described in the paragraphs above in which l i s 4, Rai and R i are
[196] In some vaiiations of formula (1 1) described in the paragraphs above in which h is 4, Ral and Rbi are Ra2 and b2 are
Figure imgf000067_0002
[197] In some variaiions of formula (1 1 ) described in the paragraphs above in which // is 4, Ra{
O O
and Rj,i are " ^\ Ra2 and 2 are r\ Ra3 and j,3 are H, and Ra4 and Ri>.i are f\ In some variations of formula (1 1) described in the paragraphs above in which _ is 4, Rai and M
Figure imgf000067_0003
In some variations of formula ( 1 1) described in the paragraphs above in which l} is 4, Ra! and &j are
Figure imgf000067_0004
In some variations of formula (1 1) described in the paragraphs above in which h is 4, Rai and R¾i are
Figure imgf000067_0005
¾ '¾ ^/ . [198] In some variations of formula (1 1 ) described in the paragraphs above in which h is 4, Rai
Figure imgf000067_0006
and j>i are
[199] In some variations of formula (1 1) described in the paragraphs above in which h is 4, Ral and Rbi are
Figure imgf000067_0007
In some variaiions of formula ( i 1) described in the paragraphs above in which / is 4, RaJ and RM are
Figure imgf000067_0008
In some variations of formula ( 1 1) described in the paragraphs above in which ; is 4, ai and ¾i are
Figure imgf000067_0009
In some variations of formula (1 1 ) described in the paragraphs above in which ¾ is 4, ai and R i are 0 0 o
· , a2 and Rb2 are ·· f\ Ra3 and Rb3 are H, and Ra and Rb are '¾· ^ .
[200] In some variations of formula (1 1) described in the paragraphs above in which h is 4, at and bi are
Figure imgf000068_0001
.
[201] In some variations of formula (11) described in the paragraphs above in which / is 4, Rai and R i are H, ^ and R 2 are H, and and Rb3 and Ra4 and R together are . In some variations of formula (11) described in the paragraphs above in which is 4, Rai and Rbi are H, R^ and Rb2 are CH3, and Ra3 and Rb3 and Ra4 and Rb together are ^ ^i n some variations of formula (11) described in the paragraphs above in which ij is 4, Ral and Ra2 are H, j,i and Rb2 are CH3, and Ra3 and Rb3 and Ra4 and Rb4 together are ^ ^^ .
[202] In some variations of formula (11) described in the paragraphs above in which / is 4, Rai and j,i are H, R^ and R 2 are '¾ , and Ra3 and R 3 and Ra4 and R 4 together are , In some variations of formula (11) described in the paragraphs above in which is 4, ai and Rbi
Figure imgf000068_0002
Ra2 and Rb2 are CH3, and Ra3 and Rb3 and Ra4 and R|,4 together are '¾ Ss^ ]n some variations of formula (11) described in the paragraphs above in which /; is 4, Ral is H, s is
CH3, Ra2 and ¾>2 are " vv and Ra3 and R 3 and Ra4 and Rb4 together are
[203] In some variations of formula (1 1) described in the paragraphs above in which i is 4, Rai
O
and Rbi are H, R^ and Rb2 are "¾ and Ra3 and Rb3 and Ra4 and Rb together are ^ r . In some variations of formula (11) described in the paragraphs above in which l} is 4, Ral and Rbi O
are Ra2 and Rb2 are CH3, and Ra3 and R 3 and Ra4 and Rb4 together are ' *· . In some variations of formula (11) described in the paragraphs above in which is 4, aj is H, i is
O
CH3, Ra2 and ¾2 are and Ra3 and R 3 and Ra and Rb together are x . ] In some variations of formula (1 ) described in the paragraphs above in which l} is 4, Rai
O O
and Rj>i are RA2 and Rb2 are and R^ and ? and RA4 and RM together are ¾ x . In some variations of formula (11) described in the paragraphs above in whi ch is 4, Rai and
O
Rfci are R^ and j>2 are "¾ ^\ and Ra3 and M and Ra4 and M together are "^- 1. In some variations of formula (1 1) described in the paragraphs above in which i} is 4, Rat and RBJ O O
are v '^A- Ra2 and Rb2 are ¾ A· / and A3 and j,3 and Ra4 and j)4 together are ¾-^ Y ¾ .
5] In some variations of formula (1 1) described in the paragraphs above in which i} is 4, Rai and Rj>i are ^*-, Ra2 and Rj,2 are '¾ and a3 and ¾3 and Ra4 and ϊ¾,4 together are
[206] In some variations of formula (11) described in the paragraphs above in which ¾ is 4, Rai and jji and Ra2 and b? together are ^ ancf j¾a3 an(j ¾b3 an(j ¾A4 ANC| Rm together are
[207] In some variations of formula (11) described in the paragraphs above in which l2 is 1, Rai and et are both H. In some vari ations of formula (11) described in the paragraphs above in which l2 is 1 , ai is H and Rbi is CH3. In some variations of formula (1 1 ) described in the paragraphs above in which is 1, ai and Rbi are both CH3. In some variations of formula (11) described in the paragraphs above in which h is 1, aj and i are
Figure imgf000069_0001
. In some variations of formula (1 1) described in the paragraphs above in which is 1, aj and R¾i are
Figure imgf000069_0002
[208] In variations of formula (1 1) described in the paragraphs above in which I? is 2, the two instances of Ra and ¾ are indicated as Rai and i and Ra2 and ¾2, respectively. In some variations of formula (1 1) described in the paragraphs above in which h is 2, each of Rai and Rbi and Ra2 and Rt,2is H. In some variations of formula (11) described in the paragraphs above in which l2 is 2, each of Rai and Rbi and R^ and Rb2 is CH3. In some variations of formula (11) described in the paragraphs above in which /? is 2, each of Rai and Ra2 is H and each of Rbi and Rb2 is CH3. In some variations of formula (1 1) described in the paragraphs above in which l2 is 2, each of Rai, Ra2, and Rj,i is H and Rb2 is CH3.
[209] In some variations of formula (11) described in the paragraphs above in which l2 is 2, each of Rai and RM is H and and R1(2 are '¾ , In some variations of formula (11) described in the paragraphs above in which l2 is 2, each of Rai and ¾i is H and Ra2 and R^i are O
- . In some variations of formula (1 1) described in the paragraphs above in which l2 is 2, each of ai and ^ is CH3 and Ra2 and j,2 are "¾ . In some variations of formula (1 1) described in the paragraphs above in which l2 is 2, each of Rai and R¾i is CH3 and and R¾2
Figure imgf000070_0001
In some variations of formula (1 1) described in the paragraphs above in which l2 is 2, Rai is H, )l is (Ί f and Ra2 and j>2 are '¾ . In some variations of formula (11) described in the
O
paragraphs above in which l2 is 2, Rai is H, j,i is CH3, and Ra2 and Rj>2 are % '¾A· . In some variations of formula (1 1) described in the paragraphs above in which l2 is 2, Ra! and ^ and
Ra2 and Rj>2 together are . In some variations of formula (1 1) described in the paragraphs above in which l2 is 2, Rai and RM are "¾ Ra2 and t,2 are '¾ . In some variations of formula (11) described in the paragraphs above in which l2 is 2, Rai and 1(i are ^ ^ and j,2 are
Figure imgf000070_0002
. In some variations of formula (1 1) described in the paragraphs above in which l2
A A
is 2, Rai and ¾i are ^ ^ and ¾2 are
[210] In variations of formula (1 1 ) described in the paragraphs above in which l2 is 3, the three instances of Ra and Rj, are indicated as ai and j,i; Ra2 and R^; and A3 and &3, respectively. In some variations of formula (11) described in the paragraphs above in which l2 is 3, In some variations of formula (11) described in the paragraphs above in which h is 3, each of Rai,Rbi, Ra2, R¾2, a3, and bs is H. In some variations of formula (1 1) described in the paragraphs above in which l2 is 3, each of Rai,¾i, ¾2, ¾2, Ra3, and 3 is CH3. In some variations of formula (1 1) described in the paragraphs above in which l2 is 3, each of Raj,Rbi, az, and Rb2, is H and each of Ra3 and
Figure imgf000071_0001
is CH3. In some variations of formula (1 1) described in the paragraphs above in which l2 is 3, each of Raj,Rbi, Raz, and ¾2, is CH3 and each of R^ and .-? is H. In some variations of formula (1 1) described in the paragraphs above in which l2 is 3, Rai is H and each of Ra2, Ra3, ¾ι, ¾2, and Rb3 is CH3. In some variations of formula ( 1 1) described in the paragraphs above in which l2 is 3, each of RaJ and Ra2 is H and each of Ra3j ¾)5 ¾2, and 3 is CH3. In some variations of formula (1 1 ) described in the paragraphs above in which l2 is 3, each of ai, Ra2, and A3 is H and each of Rbi , 2, and bs is CH3.
[211] In some variations of formula (1 1) described in the paragraphs above in which l2 is 3, each of Rai,Rbi, a2, and Rb2, is H and a3 and R 3 are " ^ ^ . In some variations of formula (1 1 described in the paragraphs above in which l2 is 3, each of Rai,Rbi, Ra2, and Rb2, is CH3 and Ra3 and Rb3 are "^- ^ . In some variations of formula (1 ) described in the paragrap above in which l2 is 3, Rai is H and each of Ra2, ¾ι, and Rb? is CH3, and RA3 and ¾3 are
Figure imgf000071_0002
. In some vari ations of formula (11) described in the paragraphs above in which l2 is 3, each of Rai and a2 is H and each of M and R¾2 is CH3, and Ra3 and .h3 are
Figure imgf000071_0003
.
[212 ] In some variations of formula (11) described in the paragraphs above in which l2 is 3,
O
each of Ra{,Rbi, Ra2, and 2, is H and ^ and ¾3 are ^ . In some variations of formula (11) described in the paragraphs above in which l2 is 3, each of RaiJ¾>i, R 2, and R 2, is CH3 and RA3
O
and ¾3 are - In some variations of formula (1 1) described in the paragraphs above in which
Figure imgf000071_0004
variations of formula (1 1) described in the paragraphs above in which l2 is 3, each of Rai and Ra2
O
is H and each of ¾ι and ¾2 is CH3, and A3 and ¾3 are ¾ A· ^ \
[213] In some variations of formula (1 1) described in the paragraphs above in which l2 is 3, Rai
V V
and Rbi are ^ Ra2 and Rb2 are '¾ ^ , and each of and ί 3 is H. in some variations of formula (1 1) described in the paragraphs above in which is 3, Ral and Rbi are "^- , Ra2 and Rb2 are '¾ ^ , and each of Ras and ^ is CH3. In some variations of formula (1 1 ) described in the paragraphs above in which l2 is 3, ai and i are " , a2 and Rb2 are , Ra3 is H, and Rb3 is CH3. In some variations of formula (1 1) described in the paragraphs above in which l2 is 3, Ral and RM are " *· , Ra2 and Rb2 are " *· and each ot Ra3 and ¾3 is H. In some variations of formula ( 1 1) described in the paragraphs above in which l2 is 3, Rai and RM are
, a2 and j,2 are
Figure imgf000072_0001
, and each of Ra3 and R¾3 is CH3. In some variations of formula ; 1 1 ) described in the paragraphs above in which l2 is 3, Rai and Rbi are "x Ra2 and Rbi are
Figure imgf000072_0002
In some variations of formula (1 1) described in the paragraphs above in which l2 is 3, B — γ O
bi are ^\ Ra2 and j,2 are 5 , and each of Ra3 and j,3 is H. In some variations of formula (1 1) described in the paragraphs above in which l2 is 3, Rai and 1(i are '¾ Ra2 and p
b2 are and each of Ra3 and Rb3 is CH3. In some variations of formula (1 1) described in the paragraphs above in which l2 is 3, RaJ and M are
Figure imgf000072_0003
, ¾3 is H, and Rb3 i s CH3. In some variations of formula ( 1 1 ) described in the paragraphs above in which l2
O
is 3, Rai and ¾i are " , Ra2 and Rb2 are and each of as and s is H. In some variations of formula ( 1 1) described in the paragraphs above in which l2 is 3, Rai and R¾i are
O
and Rb2 are ^ and each of a3 and j,3 is C¾. In some variations of formula
1 1 ) described in the paragraphs above in which 12 is 3, Ral and Rw are "¾- Ra2 and Ι¾2 are
Figure imgf000072_0004
[215] In some variations of formula (1 ) described in the paragraphs above in which l2 is 3, Ral and ¾i are
Figure imgf000073_0001
and .-?is H. In some variations of
O
formula (11) described in the paragraphs above in which l2 is 3, Rai and ¾ι are ** a2 and
Rb2 are the parag
Figure imgf000073_0002
raphs above in which l is 3, Rai and Rbi
and Rb3 is CH3. In some variations of formula (11) described in the paragraphs above in which l2
O O
is 3, Rai and R¾i are · a2 and !½ are and each of a3 and I¾3 is H. In some variations of formula (11) described in the paragraphs above in which l2 i s 3, ai and R¾i are O O
"^- Ra2 and j,2 are and each of Ra3 and Rb3 is CH3. In some variations of formula (11)
O O
described in the paragraphs above in which l2 is 3, Ra} and j,i are , a2 and i,2 are ¾ ,
Figure imgf000073_0003
[216] In some variations of formula (11) described in the paragraphs above in which l2 is 3, RaJ and bi and Ra2 and j>2 together are - and each of Ra3 and *»3 is H. In some variations of formula (11) described in the paragraphs above in which l2 is 3, Rai and Rbi and a2 and R^i together are^ " ^^i^ and each of a3 and ^sis CH3. In some variations of formula (11) described in the paragraphs above in which l2 is 3, Rai and Rbi and a2 and Rj,2 together are
, Ra3 is H, and Rb3 is CH3. In some variations of formula (11) described in the paragraphs above in which l2 is 3, Ra3 and bi and aa and ¾,2 together are , and a3 and *,3 are
In some variations of formula (11) described in the paragraphs above in which l2 is 3, Rai and i and a2 and ¾2 together are " <· and as and ¾3 are
Figure imgf000073_0004
[217] In variations of formula (11) described in the paragraphs above in which l2 is 4, the three instances of Ra and j, are indicated as Rai and Rbi; Ra2 and Rb2; aj and R^ and 34 and R¾4, respectively. In some variations of formula (11) described in the paragraphs above in which l2 is 4, In some variations of formula (1 1) described in the paragraphs above in which l2 is 4, each of RaS,RM, RA2, Rj,2, a3, ¾>3, Ra4, and &4 is H. In some variations of formula (1 1) described in the paragraphs above in which l2 is 4, each of Rai,Rt>i, a2, R¾2, a3, Rb3, a4, and ^ is CH3. In some variations of formula (11) described in the paragraphs above in which l2 is 4, each of Rai, M, 2, Rb2, 3, and ¾3 is H and each of R34 and j,4 is CH3. In some variations of formula (11) described in the paragraphs above in which l2 is 4, each of Raj, RM, Ra2, and Rj>2 is H and each of Ra3, ¾>3, Ra4, and R^ is CH3. In some variations of formula (11) described in the paragraphs above in which l2 is 4, each of Rai, RM, a2, Rb2, ¾3, and ^ is CH3 and each of R¾4 and Rb4 is H.
[218] In some variations of formula (1 1) described in the paragraphs above in which l2 is 4, each of Rai,Ra2, and A3 is H and each of R , 2, and Rb3 is CH3. In some variations of formula (1 1 ) described in the paragraphs above in which l2 s 4, Raj is H, RM is CH3, and each of a2, ¾2, a3; and Rb3 is CH3. In some variations of formula (11) described in the paragraphs above in which l2 is 4, RAS is H, R¾i is CH3, and each of R^, I¾»2, Ra3, and 1(j is H. In some variations of formula (11) described in the paragraphs above in which l2 is 4, each of Rai and R^ is H, each of RM and R|>2 is CH3, and each of RA3 and j,3 is H. In some variations of formula (1 1) described in the paragraphs above in which h is 4, each of Rai and R^ is H, each of R and R 2 is CH3, and each of Ra3 and ¾3 is CH3.
[219] In some variations of formula (11) described in the paragraphs above in which l2 is 4, Rai
Figure imgf000074_0001
and RM are H, . In some variations of formula (11) described in the paragraphs above in which l2 is 4, Ra! and RM are H,
Ra2 and ^ are H, RA3 and ^ are CH3, and RA4 and R¾4 are '¾ . In some variations of formula (11) described in the paragraphs above in which /? is 4, RAI and RM are H, ^ and Rt,2
Figure imgf000074_0002
are CH3, , In some variations of formula (11) described in the paragraphs above in which l2 is 4, RAI and are CH3, a2 and RM are CH3,
Ra3 and j,3 are CH3, and Ra4 and R¾4 are w "¾ .
In some variations of formula (1 1) described in the paragraphs above i which l2 is 4, RaJ and are H, RA2 and
Figure imgf000074_0003
, and RA4 and ¾4 are . In some variations of formula (1 1 ) described in the paragraphs above in which l2 is 4, ai and RM are H, Ra2 and Rt>2 are CH3, Ra3 and j>3 are "^- and Ra4 and ~RM are . In some variations of formula (1 1) described in the paragraphs above in which is 4, Rai and R1(i are CH3, Ra2 and
Rj,2 are CH3, Ra3 and ¾3 are
Figure imgf000075_0001
RA4 and ¾4 are "¾ . In some variations of formula (1 1 ) described in the paragraphs above in which l2 is 4, Rai is H, ¾j is CH3, Ra2 and Rj,2 are
CH3, Ra3 and R¾,3 are ¾- " , and Ra4 and ¾ are
Figure imgf000075_0002
. In some variations of formula (1 1) described in the paragraphs above in which I? is 4, RAJ is H, R¾i is CH3, Ra2 is H, j,2 is CH3,
Figure imgf000075_0003
and Rb3 are .
[221] In some variations of formula (1 1) described in the paragraphs above in which l2 is 4, Rai and Rj,i are H, R^ and j,2 are '^- Ra3 and R¾3 are '¾ and Ra4 and R¾4 are "¾ , In some variations of formula (1 1) described in the paragraphs above in which l2 is 4, and RM
Figure imgf000075_0004
are CH3, Ra2 and ¾2 are ' - , A3 and I¾3 are In some vari ations of formula (1 1) described in the paragraphs above in which I? is 4, aj is H, Rt>i is
CH3, Ra2 and b2 are "¾A3 and ¾3 are '¾S£ and RA4 and R|,4 are " V¾Si . In some variations of formula (1 1) described in the paragraphs above in which l2 is 4, ai and R¾i are < - ; and Rt>2 are N£ Ra3 and Rb3 are χ¾·S£ and Ra and Rj> are ^ .
[222] In some variations of formula 1 1 ) described in the paragraphs above in which l2 is 4, RaJ and jji are H,
Figure imgf000075_0005
. In some variations of formula (1 1) described in the paragraphs above in which h is 4, ai and M are H,
O
Ra2 and t,2 are II, Ra3 and t,3 are CH3, and Ra4 and R¾4 are '¾· *" . In some variations of formula (1 1) described in the paragraphs above in which l2 is 4, ai and R¾i are H, Ra2 and Rb2
O
are CH3, aj and t,3 are CH3, and Ra4 and R¾4 are '¾· *" . In some variations of formula (1 1) described in the paragraphs above in which l2 is 4, Rai and Rbi are CH3, Ra2 and Rb2 are CH3,
Ra3 and (,3 are CH3, and Ra4 and R¾,4 are X· . [223] In some variations of formula (1 1) described in the paragraphs above in which l2 is 4, Rai
O
and ¾i are H, Ra2 and j>2 are H, Ra3 and R¾3 are ¾ '¾A· , and Ra4 and ¾4 are v. In some variations of formula (1 1) described in the paragraphs above in which l2 is 4, 3i and R¾i are H,
O O
Ra2 and j,2 are CH3, Ra3 and ¾3 are "^- , and Ra4 and R^ are "^- In some variations of formula (1 1) described in the paragraphs above in which l2 is 4, Ra! and R^ are CH3, Ra2 and
O O
Rb2 are CH3, RA3 and Rj,3 are ^\ and Ra4 and are '¾· . In some variations ot formula (1 1) described in the paragraphs above in which l2 is 4, Rai is H, RM is CH3, Ra2 and j>2 are CH3, Ra3 and ,3 are
Figure imgf000076_0001
. In some variations of tormula (1 1) described in the paragraphs above in which l2 is 4, Rai is H, Rj,i is CH3, Ra2 is H, ¾2 is C¾, RA3 and Rj,3 are
Figure imgf000076_0002
[224] In some variations of formula (1 1) described in the paragraphs above in which l is 4, Rai
0 0 O
\A A ¾A
and Rfci are H, Ra2 and i,2 are , A3 and R¾,3 are and A4 and j,4 are ^ . In some variations of formula (1 1 ) described in the paragraphs above in which l2 i s 4, ai and R i are
( '! . Rai and ¾2 are
Figure imgf000076_0003
. In some variations of formula (1 1) described in the paragraphs above in which l2 is 4, ai is H, ¾i i s
CH3, Ra2 and R¾,2
Figure imgf000076_0004
In some variations
0 of formula (1 1) described in the paragraphs above in which l2 is 4, as and ^ are - Ra2 and Rt,2 are
Figure imgf000076_0005
.
[225] In some variations of formula (1 1) described in the paragraphs above in which l2 is 4, ai and RM are
Figure imgf000076_0006
In some variations of formula (1 1) described in the paragraphs above in which l2 is 4, Ra! and &j are ¾
"¾ Ra2 and ¾>2 are CH3, ^ and ¾3 are CH3> and R** and R 4 are f\ In some variations of formula (1 1) described in the paragraphs above in which h is 4, Ral and Rbi are
Figure imgf000077_0001
and Rb2 are H, Ra3 and Rb3 are CH3, and Ra4 and Rb4 are
Figure imgf000077_0002
[226] In some variations of formula (1 1) described in the paragraphs above in which l2 is 4, Ra!
Figure imgf000077_0003
and Rbi are '¾· <*\ In some variations of formula (1 1) described in the paragraphs above in which l2 is 4, Ra} and Rbi
O
\X X X
are ' \ Ra2 and Rb2 are '¾ ^\ ^ and Rb3 are CH3, and Ra4 and Rb4 are ' L . In some variations of formula ( 1 1 ) described in the paragraphs above in which I? i s 4, ai and Rbi are
Figure imgf000077_0004
. In some variations of formula ( 1 1 ) described in the paragraphs above in which l2 is 4, Ral and RM are
Figure imgf000077_0005
, Ra2 and Rb2 are , Ra3 and R 3 are H, and Ra4 and Rb4 are .
[227] In some variations of formula (1 1 ) described in the paragraphs above in which /? is 4, Rai and Rbi are
Figure imgf000077_0006
[228] In some variati ons of formula (1 1) described in the paragraphs above in which l2 is 4, Rai
Figure imgf000077_0007
and bi are " Ra2 and Rb2 are In some vari ations of formula (1 1) described in the paragraphs above in which h is 4, Rai and Rbi are
Figure imgf000077_0008
In some variations of formula (1 1 ) described in the paragraphs above in which 12 is 4, Ra! and bj are
Figure imgf000077_0009
In some variations of formula (1 1 ) described in the paragraphs above in which l2 i s 4, ai and R i are
O O
-¾ f- ^ Ra2 an£j iib2 are -\ ¾a3 anc Rb3 are anc| j¾a4 anc| ¾b4 are -\ .
[229] In some variations of formula (1 1) described in the paragraphs above in which /? is 4, Rai and bi are
Figure imgf000078_0001
[230] In some variations of formula (1 1) described in the paragraphs above in which l is 4, Rai and Rj,i are
Figure imgf000078_0002
, In some variations of formula (1 1) described in the paragraphs above in which l2 is 4, aj and j are
0 0 o
f\ Ra2 and Rj,2 are ' «· 33 and R¾s are CH3, and Ra4 and Rb4 are 5 , In some variations of formula (1 1) described in the paragraphs above in which l2 is 4, Ra! and R i are
Figure imgf000078_0003
. In some variations of formula (1 1) described in the paragraphs above in which l2 is 4, Rai and bi are
Figure imgf000078_0004
.
[231] In some variations of formula (1 ) described in the paragraphs above in which l2 is 4, Rai and j>i are
Figure imgf000078_0005
.
[232] In some variations of formula (1 1) described in the paragraphs above in which h is 4, Rai and Rbi are H, R^ and Rb2 are H, and ^ and Rb3 and Ra4 and Rb together are "^· V In some variations of formula (1 1) described in the paragraphs above in which l2 is 4, Ra} and i are H, Ra2 and Rb2 are CH3, and a3 and b3 and Ra4 and R 4 together are . In some variations of formula (1 1) described in the paragraphs above in which l2 is 4, ai and Ra2 are H, bi and Rb2 are CH3, and Ra3 and Rb3 and Ra4 and Rb4 together are "^- V
[233] In some variations of formula (1 1 ) described in the paragraphs above in which /? is 4, Rai and Rbi are H, R^ and Rb2 are and Ra3 and Rb3 and Ra4 and Rb4 together are - . In some variations of formula (1 1) described in the paragraphs above in which /? is 4, Rai and Rbi
Figure imgf000079_0001
, Ra2 and Rb2 are (Ί f and Ra3 and 3 and Ra4 and R¾4 together are ' ·- ¾ . In some variations of formula (11) described in the paragraphs above in which l2 is 4, Ra! is H, Rbi is a2 and ¾2 are '¾ ^\ and Ra3 and 3 and a4 and ¾4 together are
[234] In some variati ons of formula (11) described in the paragraphs above in which i2 is 4, Rai
O
and Rj,i are H, ^ and R 2 are and Ra3 and Rb3 and RA4 and RB4 together are . In some variations of formula (1 1) described in the paragraphs above in which l2 is 4, and ¾ι O
are '¾· Ra2 and Rb2 are CH3, and Ra3 and R 3 and Ra4 and RB together are ¾ , In some variations of formula (11) described in the paragraphs above in which l2 is 4, Ra! is H, Rbi is
O
CH3, Ra2 and R 2 are % A· and R^ and RB3 and RA4 and Rb4 together are 1^ Y V
[235] In some variations of formula (11) described in the paragraphs above in which l2 is 4, Rai and bi are
Figure imgf000079_0002
. In some variations of formula (11) described in the paragraphs above in which l2 is 4, Rai and
Figure imgf000079_0003
- An some variations of formula (1 1) described in the paragraphs above in which /? is 4, Ral and RBL are
Figure imgf000079_0004
and Ra and b and Ra4 and Rb4 together are Y
[236] In some variations of formula (1 1) described in the paragraphs above in which /? is 4, Rai and Rbi a
Figure imgf000079_0005
and RB2 are " <¾rS£ and and Rb3 and RA4 and RB together are
[237] In some variations of formula (1 1) described in the paragraphs above in which l2 is 4, RAJ and bi and Ra2 and R 2 together are - \ and R^ and RM and a4 and Rb4 together are 38] In some variations of formula (1 ) described in the paragraphs above ring A is
Figure imgf000080_0001
optionally substituted with halo or C1 -C6 linear or branched alkyl;
Figure imgf000080_0002
optionally substituted with halo or C1 -C6 linear or branched alkyl; or
Figure imgf000080_0003
Figure imgf000081_0001
optionally substituted with halo or C1 -C6 linear or branched aikyi.
[239] In some variations of formula (1 1) described in the paragraphs above, n is 1-4, 1-3, 1-2, 2-4, 2-3, 3-4, 1 , 2, 3, or 4,
[240] In some variations of formula (1 1) described in the paragraphs above, ring A is substituted with halo. In some variations, the halo is F, Br, I, or Ci.
[241] In some variations of formula (1 1) described in the paragraphs above, ring A is substituted with C1-C6 linear or branched alkyl (e.g., C 1 -C6, C 1 -C5, C1-C4, C1-C3, C 1-C2, C I , C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl).
[242] In some variations of formula (1 1) described in the paragraphs above, Dl is safranin-O. In some variations of formula (1 1) described in the paragraphs above, D2 is safranin-O. In some variations of formula (1 1) described in the paragraphs above, Dl and D2 are safranin-O.
[243] In some variations of formula (1 1) described in the paragraph above, the pendant phenyl ring of 1)1 is unsubstituted. In some variations of formula (1 1) described in the paragraph above, the pendant phenyl ring of Dl is substituted with 1-3 (e.g., 1-3, 1-2, I, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of Dl is substituted, the
substituents are selected independently from— NH2,— NHR,— NR2,— OH,— O",
— NHCOCH3, --NHCOR, --OCH3,—OR, --C2H5, R, and C,,l k wherein R is C1-C6 linear or branched alkyl (e.g., C1-C6, C 1-C5, C1-C4, C 1-C3, C1-C2, C I , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— N02,— NR3 T, halo (e.g., F, Br, CI, I), trihalide (e.g., --CF3, --CCI3, ---CBr3, CI : },— CN, --SO3H, --COOH, --COOR, --CHO, and — COR, wherein R is C1-C6 linear or branched alkyl (e.g., C1-C6, C1-C5, C1-C4, C 1-C3, Cl - C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
[244] In some variations of formula (11) described in the paragraph above, the pendant phenyl ring of D2 is unsubstituted. In some variations of formula (1 1) described in the paragraph above, the pendant phenyl ring of D2 is substituted with 1-3 (e.g., 1 -3, 1-2, 1 , 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of 1)2 is substituted, the substituents are selected independently from— -NH2,— NHR,— R2,— OH,— O",
— NHCOCH3, XI li OR.— OCH3,—OR,— C2H5,— R, and G,i k wherein R is C1-C6 linear or branched alkyl (e.g., C1-C6, C1-C5, C1-C4, C 1-C3, C1-C2, CI , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl ). In some embodiments in which the pendant phenyl ring of 1)2 is substituted, the substituents are selected independently from— O?,— NR3 , halo (e.g., F, Br, CI, I), trihalide (e.g., --CF3, --CCI3, ---CBr3, --CI3),— CN, --SO3H, COO! ! --COOR, --CHO, and —COR, wherein R is C1-C6 linear or branched alkyl (e.g., C 1-C6, C1-C5, C1-C4, C 1-C3, Cl- C2, CI , C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
[245] In some of the variations of formula (11) described above, Dl and D2 are safranin-0 moieties, as shown in formula (11a):
Figure imgf000082_0001
("^ a) , in which , h, n, ring A, Rai,
Rbi ¾2, and Rj,2 are as described in the paragraphs above, Ri, R2, R3, R4, Rs, and ¾
independently are absent or independently are selected from— NH2,— NHR,— NR2,— OH, ( )", Xi lC CH ;, M (COR, --OCH3, OR, C,\ , --R,—C6H5,— ()2, --NR3 +, halo (e.g., I '. Br, CI, I), trihalide (e.g., CF3, --CC13, ---CBr3, Ch i— CN, --SO3H, { ()()! !. —CGOR,—CHO, and— COR), and R is C 1-C6 linear or branched alkyl (e.g. , C1-C6, C1-C5, C1-C4, C1 -C3, C 1-C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4- C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl).
[246] One of skill in the art can readily visualize and prepare other cationic multimers falling within formula (1 1) in which other cationic dye moieties are used in place of one or both of the safranin-0 moieties.
Some cationic dye dimers fall within formula (12):
Figure imgf000083_0001
( s in which each of Dl and D2 is a cationic dye moiety; l l2, n, Oj, and o2 independently are 1 -4; ring A is aryl, heteroaryl, cycloaikyi, or heterocyciyl; for each independent instance of ai and Rj>i. Rai and Rbi ( 1 ) independently are H or CH3, or (2) Rai and R¾i are
Figure imgf000083_0002
or (3) two of CRaiRbi are
; for each independent instance of a2 and Rj)2. Ra2 an R¾2 (1 ) independently are H or
O
CH3, or (2) a2 and Rt>2 are "^- or ? or (3) two of CRa2Rb2 are v for each independent instance of Rcl and and Rdl (1) independently are H or CH3, or (2) and
Rdi are '¾ or ^ nr †wn of Κ„, ϊ¾.« are. - for each independent instance of c2
— j (3 and R,j2> Rc2 and
Figure imgf000083_0003
(1) independently are H or CH3, or (2) c2 and ¾2 are W orA or
Figure imgf000083_0004
[248] In some variations of formula (12), the catiomc dye moiety is selected from the group consisting of safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue. In some variations of formula (12), Dl and D2 are different cationic dye moieties. In other variations of formula (12), Dl and D2 are the same cationic dye moiety. [249] In some variations of formula (12) described in the paragraphs above, is 1-4, 1 -3, 1-2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[250] In some variations of formula (12) described in the paragraphs above, is 1 -4, 1-3, 1-2, 2-4, 2-3, 3-4, 1 , 2, 3, or 4.
[251] In some previous variations of formula (12) described in the paragraphs above, oi is 1-4, 1-3, 1 -2, 2-4, 2-3, 3-4, 1 , 2, 3, or 4.
[252] In some previous variations of formula (12) described in the paragraphs above, o2 is 1-4, 1-3, 1 -2, 2-4, 2-3, 3-4, 1 , 2, 3, or 4,
[253] In some variations of formula (12) described in the paragraphs above in which / is 1, ai and Rjji are both H. In some variations of formula (12) described in the paragraphs above in which / is 1, Raj is H and ¾j is CH3. In some variations of formula (12) described in the paragraphs above in which lj is 1 , Rai and M are both CH3. In some variations of formula (12) described in the paragraphs above in which lj is 1, Rai and ¾ι are V "¾Si . In some variations of
O
formula (12) described in the paragraphs above in which l} is 1, Raj and &j are '¾· ^ .
[254] In variations of formula (12) described in the paragraphs above in which U is 2, the two instances of Ra and Rb are indicated as ai and M and Ra2 and Rb2, respectively. In some variations of formula (12) described in the paragraphs above in which l} is 2, each of Rai and bt and Ra2 and Rj,2 is H. In some variations of formula (12) described in the paragraphs above in which // is 2, each of aj and &j and ^ and Rj,2 is CH3. In some variations of formula (12) described in the paragraphs above in which is 2, each of Rai and Ra2 i s H and each of Rbi and b2 is CH3. In some variations of formula (12) described in the paragraphs above in which l} is 2, each of Rai, Ra2, and ¾i is H and R¾2 is CH3.
[255] In some variations of formula (12) described in the paragraphs above in which lj is 2, each of Rai and Rm is H and Ra2 and Rb2 are "¾ . In some variations of formula ( 12) described in the paragraphs above in which lj is 2, each of Rai and R¾i is H and ^ and i,2 are O
'¾· . In some variations of formula (12) described in the paragraphs above in which lj is 2, each of Rai and w is CH3 and Ra2 and Rb2 are . In some variations of formula (12) described in the paragraphs above in which i} is 2, each of Rai and RM is CH3 and ^ and Rj,2 O
are
In some variations of formula (12) described in the paragraphs above in which i is 2, Rai is H, bi is CH3, and Ra2 and Rj,2 are
Figure imgf000085_0001
. In some variations of formula (12) described in the
O
paragraphs above in which l is 2, Rai is H, R¾i is CH3, and Ra2 and b2 are ' 1 ^\ In some variations of formula (12) described in the paragraphs above in which /; is 2, Rai and Rbi and
Ra2 and t,2 together are ^ In some variations of tormula (12) described in the paragraphs above in which li is 2, RaS and R¾i are "^- ^ and R¾2 are "^- , In some variations of tormula (12) described in the paragraphs above in which ¾ is 2, Ra! and R^ are '¾ aa and b2 described in the paragraphs above in which U is 2,
Figure imgf000085_0002
Ral and R&j are Ra2 and Rb2 are
[256] In variations of formula (12) described in the paragraphs above in which // is 3, the three instances of Ra and j, are indicated as Rai and bi; Ra2 and Rj,2; and as and ¾a, respectively. In some variations of formula (12) described in the paragraphs above in which l} is 3, In some variations of formula (12) described in the paragraphs above in which i} is 3, each of Rai,Rt>i, Ra2, Rb2, Ra3, and Rb3 is H. In some vari ations of formula (12) described in the paragraphs above in which ; is 3, each of Rai,Rbi, Ra2, Rb2, a3, and Rb3 s (Ί I ; In some variations of formula (12) described in the paragraphs above in which // is 3, each of Rai,Rbi, Ra2, and Rb2, is H and each of Ra3 and Rb3 is CH3. In some variations of formula (12) described in the paragraphs above in which // is 3, each of Rai,Rbi, Ra2, and Rb2, is CH3 and each of as and b.? is H. In some variations of formula (12) described in the paragraphs above in which ¾ is 3, Rai is H and each of Ra2, Ra3; Rbi, b2, and b3 is CH3. In some variations of formula (12) described in the paragraphs above in which ¾ is 3, each of Rai and Ra2 is H and each of Ra3; RM, Rb2, and Rbj is CH3. In some variations of formula ( 2) described in the paragraphs above in which / is 3, each of Rai, Ra2, and a3 is H and each of Rbi, R¾2, and ¾3 is CH3. [257] In some variations of formula (12) described in the paragraphs above in which l} is 3, each of Rai,¾i, Ra2, and J¾,2, is H and a3 and ¾3 are w "¾ . In some variations of formula (12) described in the paragraphs above in which is 3, each of Rai,Rbi, a2, and Rj>2, is CH3 and Ra3 and Rb3 are "^- . In some variations of formula (12) described in the paragrap above in which is 3, Rai is H and each of Ra2, R|>i, and Rb2 is CH3, and Ra3 and Ri)3 are
Figure imgf000086_0001
. In some variations of formula (12) described in the paragraphs above in which lj is 3, each of Rai and Ra2 is H and each of Rbi and ¾2 is CH3, and a3 and Rb3 are
Figure imgf000086_0002
[258] In some variations of formula (12) described in the paragraphs above in which l} is 3,
O
each of Rai,Rbi, Ra2, and j,?, is H and R^ and b3 are . In some variations of formula (12) described in the paragraphs above in which lj is 3, each of Rai,Rbi, Ra2, and RM, is CH3 and Ra3
O
and j>3 are ^\ In some variations of formula (12) described in the paragraphs above in which
O
// is 3, Rai is H and each of R^, Rbi, and j,2 is C¾, and and Rb3 are '¾· ** , In some variations of formula (12) described in the paragraphs above in which ij is 3, each of ai and Ra2
O
is H and each of i and ¾2 is CH3, and as and Rb3 are "^- ^\
[259] In some variations of formula (12) described in the paragraphs above in which l} is 3, Ral and Rw are '¾ ?~ , Ra2 and b2 are '¾ , and each of and R!)3 is H. In some variations of formula (12) described in the paragraphs above in which h i s 3, Rai and R¾i are "¾ ** , Ra2 and Rj,2 are "¾ , and each of Ra3 and s^ is CH3. In some variations of formula (12) described in the paragraphs above in which /2 is 3, Rai and ¾ι are '¾ Ra2 and ½ are 'x , ^ is H, and Rb3 is ( I f ;. In some variations of formula (12) described in the paragraphs above in which 1} i s 3, Rai and R i are "^- , Ra2 and R|>2 are '¾ and each of as and R s is H. In some variations of formula (12) described in the paragraphs above in which h is 3, ai and &j are la
(12) d
Figure imgf000087_0001
are
"¾ , Raj is H, and Rh3 is C¾.
[260] In some variations of formula (12) described in the paragraphs above in which / is 3, Rai and ¾i are
Figure imgf000087_0002
and each of and Rj>3 is H. In some variations of formula (12) described in the paragraphs above in which is 3, Rai and R i are '¾· , Ra2 and
Figure imgf000087_0003
some variations of formula (12) described in
O
the paragraphs above in which l} is 3, ai and M are "¾ ^\ Ra2 and j,2 are 5 , R^ is H, and Rb3 is CH3. In some variations of formula (12) described in the paragraphs above in which //
O
is 3, Rai and R¾i are '¾ ^\ Ra2 and Rs,2 are '¾· f" , and each of aj and Rb3 is Ii In some variations of formula (12) described in the paragraphs above in which i} is 3, Ra! and ¾j are
Figure imgf000087_0004
and each of A3 and b3 is CH3. In some variations of formula
(12) described in the paragraphs above in which / is 3, RaJ and M are "^- Ra2 and b2 are O
Figure imgf000087_0005
[261] In some variations of formula (12) described in the paragraphs above in which l} is 3, Rai
O 0
and RM are ¾ ** A· f <*\ Ra2 and R 2 are ¾ '¾A· and each of R¾3 and Rb3 is H. In some variations of
O
formula (12) described in the paragraphs above in which h is 3, Rai and R¾i are f\ Ra2 and
O
b2 are ¾ A and each of A3 and b3 is CH3. In some variations of formula (12) described in
O O
the paragraphs above in which i} is 3, Ral and ¾ι are ¾ 'Ai Ra2 and b2 are ¾A , is H, and Rbsis CH3. In some variations of formula (12) described in the paragraphs above in which
O O
is 3, Rai and ¾i are *" , Ra2 and Rb2 are "»- and each of ¾3 and Rb3 is H. In some variations of formula (12) described in the paragraphs above in which l} is 3, Rai and R¾i are O O
-\ and Rb2 are and each of and Rb3 is CH3. In some variations of formula (12)
O O
described in the paragraphs above in which // is 3, Ra} and are "*· , Ra2 and i,2 are '¾· ¾ ,
Figure imgf000088_0001
[262] In some variations of formula (12) described in the paragraphs above in which i} is 3, Rai and RM and Ra2 and Rj>2 together are - and each ot RA3 and .b3 is H. In some variations of formula (12) described in the paragraphs above in which lj is 3, ai and M and Ra2 and Rb2 together are ^ ^i^ anc each of Ra3 and R^is CH3. In some variations of formula (12) described in the paragraphs above in which / is 3, Rai and RM and Ra2 and Rj,2 together are V V
, Ra3 is H, and ^ is CH3. In some variations of formula (12) described in the paragraphs above in which // is 3, Ra3 and M and a2 and R¾,2 together are and Ra3 and i,3 are
'¾ . In some variations of formula (12) described in the paragraphs above in which is 3, ai
O
and M and Ra2 and ¾2 together are <· and a3 and R¾3 are <- .
[263] In variations of formula (12) described in the paragraphs above in which ¾ is 4, the three instances of Ra and j, are indicated as Rai and ; Ra2 and Rj,2; as and Rj,3; and 34 and R¾4, respectively. In some variations of formula (12) described in the paragraphs above in which l} is 4, In some variations of formula (12) described in the paragraphs above in which lj is 4, each of Rai,¾i, ¾2, ¾2, ¾3, ¾3, Ra4, and M is H. In some variations of formula (12) described in the paragraphs above in which h is 4, each of Raj,Rt>i, 2, 2, as, R&3, A4, and ¾4 is CH3. In some variations of formula (12) described in the paragraphs above in which l} is 4, each of Rai, M, Ra2, Rb2, a3, and &sis H and each of A4 and MIS CH3. In some variations of formula (12) described in the paragraphs above in which h is 4, each of Rai, M, a2, and Rj,2is H and each of Ra3, Rb3; RA4. and ^is CH3. In some variations of formula (12) described in the paragraphs above in which h is 4, each of Rai, , Ra2, ¾>2, a3, and ¾3is CH3 and each of RA4 and MIS H. [264] In some variations of formula (12) described in the paragraphs above in which l} is 4, each of Rai,Ra2, and Ra3 is H and each of w, Rb2, and j,3 is CH3. In some variations of formula (12) described in the paragraphs above in which is 4, Raj is H, M is CH3, and each of Ra2, ¾2, Ra3. and Rj>3 is CH3. In some variations of formula (12) described in the paragraphs above in which lj is 4, Rai is H, R1(i is CH3, and each of R^, R¾2, Ra3, and ¾3 is H. In some variations of formula ( 12) described in the paragraphs above in which l} is 4, each of Rai and a2 i s H, each of RM and RB2 is CH3, and each of and j,3 is H. In some variations of formula (12) described in the paragraphs above in which i} is 4, each of Rai and is H, each of Rm and Rb2 is CH3, and each of A3 and &3 is CH3.
[265] In some variations of formula (12) described in the paragraphs above in which I} is 4, Rai and RM are H, Ra2 and ϊ¾2 are H, Ra3 and R1(3 are H, and Ra4 and Rb are '¾ . In some variations of formula (12) described in the paragraphs above in which is 4, Ral and RM are H,
Ra2 and are H, Ra3 and Rb3 are CH3, and A4 and Rb4 are "¾ . In some variations of formula (12) described in the paragraphs above in which l} is 4, aj and R¾i are H, ^ and ¾2 are CH3, as and R¾3 are CH3, and RA4 and &4 are " L . In some variations of formula (12) described in the paragraphs above in which ; is 4, Rai and M are CH3, Ra2 and ¾2 are CH3,
Ra3 and Rj,3 are CH3, and A and RM are '¾· ^ ,
[266] In some variations of formula (12) described in the paragraphs above in which / is 4, as and Rbj are H, ^ and Rb2 are H, Ra3 and j,3 are '^- , and Ra4 and (,4 are "^- . In some variations of formula (12) described in the paragraphs above in which lj is 4, Rai and R¾i are I:
Ra2 and Rb2 are CH3, Ra3 and j,3 are
Figure imgf000089_0001
. In some variations of formula ( 12) described in the paragraphs above in which l} is 4, ai and ¾i are CH3, Ra2 and b2 are CH3, RA3 and RM are "¾ , and RA4 and I¾4 are '¾ . In some variations of formula (12) described in the paragraphs above in which lj is 4, RAI is H, M is CH3, RA2 and ^ are
('! ! :, Ra3 and R¾,3 are , and Ra and ¾ are " *· . In some variations of formula (12) described in the paragraphs above in which is 4, Rai is H, R¾i is CH3, Ra2 is H, ¾ is CH3, RA3 and j,3 are
Figure imgf000090_0001
[267] In some variations of formula (12) described in the paragraphs above in which l} is 4, Rai
Figure imgf000090_0002
and Rj>i are H, Ra2 and j>2 are , Ra3 and ¾3 are "¾ <* and Ra4 and Rb4 are '¾ . In some vari ations of formula (12) described in the paragraphs above in which lj is 4, Rai and Rbi are CH3, ^ and Rb2 are "¾ , RA3 and Ε*3 are "¾ , and RA4 and RM are "*· . In some variations of formula scribed in the paragraphs above in which lj is 4, Rai is H, ¾i is
CH3, Ra2 and ¾2 are
Figure imgf000090_0003
as and R 3 are '¾· and Ra4 and R|>4 are . In some variations of formula (12) described in the paragraphs above in which ; is 4, ai and M are
. _ w
"¾ Ra2 and R^ are '¾ Ra3 and j,3 are "^- ^\ and RA and Rj,4 are '¾ ^\
[268] In some variations of formula (12) described in the paragraphs above in which !j is 4, Rat
O
and Rbi are H, R^ and Rj,2 are H, as and ¾3 are H, and RA4 and Rb4 are ^ . In some variations of formula (12) described in the paragraphs above in which is 4, aj and 1(j are H,
O
Ra2 and RB2 are H, Ra3 and RB3 are CH3, and Ra4 and M are A · ^c-* . In some variations of formula (12) described in the paragraphs above in which ; is 4, ai and ¾i are H, Ra2 and (,2
O
are CH3, R^ and j,3 are CH3, and Ra4 and R 4 are · . In some variations of formula (12) described in the paragraphs above in which // is 4, Ra} and j,j are CH3, Ra2 and (,2 are CH3,
A -
Ra3 and RM are CH3, and Ra4 and R¾4 are .
[269] In some variations of formula (12) described in the paragraphs above in which lj is 4, ai
O
and RBJ are H, R^ and RB2 are H, Ra3 and ¾3 are and Ra4 and j,4 are v. In some variations of formula (12) described in the paragraphs above in which ij is 4, RAL and w are H,
A A
Ra2 and Rb2 are CH , as and B3 are "¾· and RA4 and Rb4 are In some variations of formula (12) described in the paragraphs above in which is 4, Rai and ¾ι are CH3, Ra2 and
O O
2 are CH3, Ra3 and ¾ are "^- and A4 and ¾4 are ^\ In some variations of formula (12) described in the paragraphs above in which lj is 4, Rai is H, ¾i is C¾, Ra2 and ¾2 are
Figure imgf000091_0001
described in the paragraphs above in which / is 4, RaJ is H, R¾i is CH3, Ra2 is H, ¾2 is CH3, Ra3
O O
and Rj,3 are ¼ "^A- ^\ and Rai and RM are ¼ · ^(\
[270] In some variations of formula (12) described in the paragraphs above in which i} is 4, Rai
0 0 o
and R[»i are H, Ra2 and .b2 are'^ Ra3 and R¾3 are and RA4 and M are' 4- ^\ In some variations of formula ( 12) described in the paragraphs above in which l} is 4, Rai and ¾i are
0 0 o
CH , Ra2 and ¾>2 are A / Ra3 and s,3 are % and Ra4 and j,4 are ¾ A ¾ . In some variations of formula (12) described in the paragraphs above in which is 4, Rai is H, Rbi is
0 0 o
CH , Ra2 and ¾>2 are'¾A Ra3 and R¾3 are "¾ A and A4 and RM are "¾A ^\ In some variations
0 of formula (12) described in the paragraphs above in which l} is 4, Rai and M are ¾ ' -A , Ra2 and R¾2 are
Figure imgf000091_0002
.
[271] In some variations of formula (12) described in the paragraphs above in which / is 4, Rai
*T 7 O and j,i are Ra2 and ϊ¾>2 are H, aj and Rb3 are H, and a4 and ^ are "^- In some variations of formula (12) described in the paragraphs above in which h is 4, Raj and &j are
'¾ r " , Ra2 and Rj>2 are CH3,
Figure imgf000091_0003
and R1(3 are CH3, and Ra4 and Rb4 are ¾ A· / In some variations of formula (12) described in the paragraphs above in which Jj is 4, Rai and Rbl are
Figure imgf000091_0004
Ra2
O
and j>2 are H, Ra3 and Rj>3 are CH3, and Ra4 and j,4 are . [272] In some variations of formula (12) described in the paragraphs above in which U is 4, Rai
Figure imgf000092_0001
and Ri>i are In some variations of formula (12) described in the paragraphs above in which // is 4, Rai and bi
Figure imgf000092_0002
are · f\ In some variations of formula (12) described in the paragraphs above in which l} is 4, Ra) and Rb! are
Figure imgf000092_0003
Ra3 and RM are CH3, and Ra4 and Rb4 are '¾· In some variations of formula (12) described in the paragraphs above in which l} is 4, R;, i and Rb! are
Figure imgf000092_0004
a2 and Rb2 are Ra3 and R!)3 are H, and Ra and RM are
[273] In some variations of formula (12) described in the paragraphs above in which l} is 4, Rai
Figure imgf000092_0005
and bi are . [274] In some variations of formula (12) described in the paragraphs above in which lj is 4, Rai
Figure imgf000092_0006
and R { are are * In some variations of formula (12) described in the paragraphs above in which is 4, Rai and R l are
Figure imgf000092_0007
In some vari ations of formula (12) described in the paragraphs above in which is 4, Rai and R i are
Figure imgf000092_0008
* Ra3 and Rb3 are CH3, and Ra4 and Rb4 are In some vari ations of formula (12) described in the paragraphs above in which /; is 4, Rai and RM are
Figure imgf000092_0009
are
[275] In some variations of formula (12) described in the paragraphs above in which // is 4, Rai
Figure imgf000092_0010
and Rbi are ¾ Ra2 and Rb2 are ' ¾· ^\ [276] In some variations of formula (12) described in the paragraphs above in which l} is 4, Rai and ¾i are
Figure imgf000093_0001
In some variations of formula (12) described in the paragraphs above in which h i s 4, ai and R¾i are 0 0 o
A Α A
'¾· Ra2 and Rb2 are Ra3 and Rb3 are CH3, and Ra4 and Rj>4 are ^ . In some variations of formula (12) described in the paragraphs above in which lj i s 4, Ra! and Rb! are 0 0 o
¾A ¾·^·
Ra2 and Rb2 are '^- Ra3 and Rb3 are CH3, and Ra4 and Rb4 are r\ In some variations of formula (12) described in the paragraphs above in which l} is 4, Ra! and Rb! are 0 0 o
< , Ra2 and Rb2 are ' *· Ra3 and ¾3 are H, and Ra4 and Rb4 are '¾· f\
[277] In some variations of formula (12) described in the paragraphs above in which l} is 4, Rai and Rbi are
Figure imgf000093_0002
.
[278] In some variations of formula (12) described in the paragraphs above in which i is 4, Rai and Rbi are H, and Rb2 are H, and Ra3 and Rb3 and Ra4 and Rb4 together are "^- . In some variations of formula (12) described in the paragraphs above in which l} is 4, Ral and Rbi are H, R^ and Rb2 are CH3, and Ra3 and Rb3 and Ra4 and RM together are '^- x . In some variations of formula (12) described in the paragraphs above in which ; is 4, ai and Ra2 are H,
Rbi and Rb2 are CH3, and Ra3 and Rb3 and Ra4 and Rb4 together are "*· [279] In some variations of formula (12) described in the paragraphs above in which l} is 4, ai
• 5S
and bi are H, R^ and Rb2 are '¾ ^\ and Ra3 and Rb3 and Ra4 and Rb4 together are ν¾· . In some variations of formula (12) described in the paragraphs above in which / is 4, Ral and bi
Figure imgf000093_0003
, Ra2 and Rb2 are CH3, and Ra3 and Rb3 and Ra4 and RM together are ' L x . In some variations of formula (12) described in the paragraphs above in which l} is 4, Rai is H, bi is
CH3, Ra2 and Rb2 are '¾ and Ra3 and R 3 and Ra4 and Rb4 together are ^ . [280] In some variations of formula (12) described in the paragraphs above in which l} is 4, Rai
O
and ¾i are H, Ra2 and R 2 are ¼ A and RA3 and R 3 and RA4 and R 4 together are ¾ . In some variations of formula (12) described in the paragraphs above in which lj is 4, Rai and Rbi
O
are A Ra2 and Rb2 are CH3, and Ra3 and Rb3 and Ra4 and RM together are "^- . In some variations of formula (12) described in the paragraphs above in which lj i s 4, Ra! is H, Rb{ i s
O
CH3, Ra2 and Rb2 are · and RA3 and B3 and Ra4 and Rb4 together are ¾ .
[281] In some variations of formula (12) described in the paragraphs above in which i} is 4, Rai
Figure imgf000094_0001
In some variations of formula 12) described in the paragraphs above in which i} is 4, Raj and
Rbi
Figure imgf000094_0002
. In some variations of formula ( 12) described in the paragraphs above in which is 4, Rai and Rbi O O
are % -A ^ , Ra2 and Rb2 are ¾A , and A3 and 3 and RA4 and B4 together are ¾^ Y V
[282] In some variations of formula (12) described in the paragraphs above in which h is 4, Rai and M are L Ra2 and Rb2 are '¾ and as and R 3 and Ra4 and Rb4 together are
[283] In some variations of formula (12) described in the paragraphs above in which // is 4, ai and jji and Ra2 and R 2 together are ' '- and aj and Rb3 and Ra4 and B4 together are
[284] In some variations of formula (12) described in the paragraphs above in which /? is 1, Rai and j>i are both H. In some variations of formula (12) described in the paragraphs above in which l2 is I, Rai is H and Rbi is CH3. In some variations of formula (12) described in the paragraphs above in which l2 is 1, Rai and Rbi are both CI-I3. In some variations of formula (12) described in the paragraphs above in which l2 is 1, Rai and bi are . In some variations of
O
formula (12) described in the paragraphs above in which l2 is 1 , ai and Rbi are ^\
[285] In variations of formula (12) described in the paragraphs above in which I? is 2, the two instances of Ra and Rb are indicated as Rai and Rbi and Ra2 and ¾2, respectively. In some variations of formula (12) described in the paragraphs above in which l2 is 2, each of Rai and M and Ra2 and R|,2 is H. In some variations of formula (12) described in the paragraphs above in which l2 is 2, each of Rai and R i and ^ and ¾2 is CH3. In some variations of formula (12) described in the paragraphs above in which l? is 2, each of Rai and Ra2 is H and each of bt and Rb2 is CH3. In some variations of formula (12) described in the paragraphs above in which l2 is 2, each of Ra{, Ra2, and bj is H and Rb2 is CH3.
[286] In some variations of formula (12) described in the paragraphs above in which l2 is 2,
Figure imgf000095_0001
each of Rai and Rbi is H and , In some variations of formula (12) described in the paragraphs above in which l2 is 2, each of Rai and Rbi is H and Ra2 and Rb2 are O
. In some variations ot formula (12) described in the paragraphs above in which l2 is 2, each of ai and bi is CH3 and Ra2 and 2 are "¾ . In some variations of formula (12) described in the paragraphs above in which l2 is 2, each of Rai and R¾i is CH3 and and Rb2 O
are ·- ^ .
In some variations of formula (12) described in the paragraphs above in which l2 i s 2, Rai is H,
M)l is CII3, and Ra2 and 2 are "¾ , jn some variations of formula (12) described in the
O
paragraphs above in which l2 is 2, Rai is H, R i is CH3, and Ra2 and Rb2 are ¾ '¾· . In some variations of formula (12) described in the paragraphs above in which l2 is 2, Ra! and Rb! and
Ra2 and Rb2 together are V In some variations of formula ( 12 described in the paragraphs above in which /? is 2, Rai and Rb
Figure imgf000095_0002
. In some variations of formula (12) described in the paragraphs above in which I? is 2, Ral and ¾i are *" Ra2 and O
Rj,2 are ' *· ^\ In some variations of formula (12) described in the paragraphs above in which l2
O Q
is 2, Ral and bi are '¾· and R *i 2 are
[287] In variations of formula (12) described in the paragraphs above in which l2 is 3, the three instances of Ra and R¾ are indicated as Rai and Rbi; a2 and Rj,2; and Ra3 and Ry, respectively. In some variations of formula (12) described in the paragraphs above in which is 3, In some variations of formula (12) described in the paragraphs above in which l2 i s 3 , each of Rai,Rjt>i, a2, ¾)2, a3, and Rbs is H. In some variations of formula (12) described in the paragraphs above in which l2 is 3, each of R i,Rbi, ¾2, Ri)2, Ra3, and ^ i CH3. In some variations of formula (12) described in the paragraphs above in which l2 is 3, each of Rai,Rbi, Ra2, and Rj>2, is H and each of Ra3 and Ri»3 is CH3. In some variations of formula (12) described in the paragraphs above in which l2 is 3, each of Rai,Rbi, R¾2, and Rj,2, is CH3 and each of Ra3 and Rs>3 is H. In some variations of formula (12) described in the paragraphs above in which l2 is 3, Raj is H and each of Ra2, Raj, R|>i, i>2, and ^ is CH3. In some variations of formula (12) described in the paragraphs above in which !.? is 3, each of Rai and Ra2 is H and each of Ra3, RM, ¾2, and R|,3 is CH3. In some variations of formula (12) described in the paragraphs above in which l2 is 3, each of Ra{, Ra2, and Ra3 is H and each of w, K, and Rt,3 is CH3.
[288] In some variations of formula (12) described in the paragraphs above in which l2 is 3, each of Rai,Rbi, Ra2, and Rt,2, is H and ^ and i»3 are '¾ . In some variations of formula (12) described in the paragraphs above in which l2 is 3, each of Rai,Rbj, a2, and Rj>2, is CH3 and Ra3 and Rb3 are " . In some variations of formula (12) described in the paragraphs above in which l2 is 3, Rai is H and each of Ra2, Rt>i, and Rb2 is CH3, and Ra and Rb3 are ^ . In some variations of formula (12) described in the paragraphs above in which l2 is 3, each of Rai and Ra2 is H and each of Rbi and ¾2 is CH3, and Ra3 and Rj,3 are "¾ *" \
[289] In some variations of formula (12) described in the paragraphs above in which l2 is 3,
O
each of Rai,Rbi, Ra2, and j,2, is H and R^ and Rj,3 are . In some variations of formula (12) described in the paragraphs above in which l2 is 3, each of Rai,Rbi, Ra2, and Rb2, is CH3 and Ra3 O
and R ? are . In some variations of formula (12) described in the paragraphs above in which
O
h is 3, Rai is H and each of Rbi, and ¾2 is CH3, and and Rb3 are , In some variations of formula (12) described in the paragraphs above in which l2 is 3, each of ai and Ra2
O
is H and each of bi and Rb2 is CH , and Ra3 and Rb3 are "^- ^\
}] In some variations of formula (12) described in the paragraphs above in which l2 is 3, Ral and R i are '¾ ?~ , Ra2 and Rb2 are '¾ , and each of and Rb3 is H. In some variations ot formula (12) described in the paragraphs above in which l2 is 3, ai and R¾i are "¾ Ra2 and Rb2 are "¾ and each of a3 and Rb3 is CH3. In some variations ot formula (12) described in the paragraphs above in which l2 is 3, Rai and Rbi are '¾ Ra2 and Rb2 are 'x , R^ is H, R 3 is CH3. In some variations of formula ( 12) described in the paragraphs above in which l2 is 3,
Rai and RM are '¾ ^ , Ra2 and R 2 are , and each of Ra3 and Rb3 is H. In some variations of formula (12) described in the paragraphs above in which l2 is 3, Rai and Rbi are
Figure imgf000097_0001
, Ra2 and R 2 are '¾ ^\ and each of Ra3 and 3 i s CH3. In some variations of formula (12) described in the paragraphs above in which l2 is 3, Rai and i are "¾ Ra2 and Rb2 are '¾ Ra3 is H, Rb3 is CH3.
[291] In some variations of formula (12) described in the paragraphs above in which l2 is 3, Ral and Rbi are "¾ ^*, Ra2 and Rb2 are and each of Ra3 and Rb3 is H. In some variations of formula (12) described in the paragraphs above in which h is 3, ai and bi are
Figure imgf000097_0002
Figure imgf000097_0003
some variations of formula (12) described the paragraphs above in which l2 is 3,
Figure imgf000098_0001
and Rb3 is CH3. In some variations of formula (12) described in the paragraphs above in which l2
O
is 3, Rai and R¾i are '¾ ^\ Ra2 and Rs,2 are '¾· f" , and each of Ra3 and Rs,3 is H. In some variations of formula (12) described in the paragraphs above in which l2 is 3, Ral and w are
O
a2 and Rb2 are X , and each of Ra3 and b3 is CH3. In some variations of formula
( 12) described in the paragraphs above in which l2 is 3, Rai and Rw are "^- , Ra2 and j,2 are
Figure imgf000098_0002
[292] In some variations of formula (12) described in the paragraphs above in which l2 is 3, Rai
O O
and Rbi are U *¾·-U f\ Ra2 and R^ are ¼ '¾A , and each of Ra3 and b3 is H, In some variations ot
O
formula (12) described in the paragraphs above in which l2 is 3, Rai and R¾i are ^\ Ra2 and
O
j,2 are ¾ A and each of A3 and b3 is CH3. In some variations of formula (12) described in
O O
the paragraphs above in which l2 is 3, Ral and ¾i are ¾ ' A */" , Ra2 and R¾2 are ¾A , is H, and Rb3 is ( I f ;. In some variations of formula (12) described in the paragraphs above in which l2
O 0
is 3, ai and 1(i are **A */" , Ra2 and ¾2 are ¾ '¾Α· / and each of R¾3 and ¾3 is H. In some variations of formula ( 12) described in the paragraphs above in which h is 3, Rai and ¾i are
O O
'¾A· / Ra2 and j,2 are ¾ '¾A· and each of A3 and b3 is CH3. In some variations of formula (12)
O O
described in the paragraphs above in which l2 is 3, Ral and M are ¾A , Ra2 and
Figure imgf000098_0003
are ' LA
Figure imgf000098_0004
[293] In some variations of formula (1 2) described in the paragraphs above in which l2 is 3, Rat and bi and Ra2 and !½ together are and each of Ra3 and ϊ¾3 is H. In some variations of formula (12) described in the paragraphs above in which l2 is 3, Rai and bi and ^ and ¾2 together are and each of Ra3 and R 3 is CH3. In some variations of formula (12) described in the paragraphs above in which l2 is 3, Rai and I¾i and Ra2 and Rb2 together are
RA3 is H, and ¾3 is CH3. In some variations of formula (12) described in the paragraphs above in which l2 is 3, Rai and ¾i and and ¾2 together are '*· 1 , and Ra3 and Rb3 are
" *· . In some variations of formula (12) described in the paragraphs above in which l2 is 3, Rai
9
and Rjji and Ra2 and Rb2 together are ^ and R and Rt>3 are .
[294] In variations of formula (12) described in the paragraphs above in which l2 is 4, the three instances of Ra and Rb are indicated as Ral and !¾; Ra2 and Rb2; Ra3 and Rb3; and Ra4 and R¾4, respectively. In some variations of formula (12) described in the paragraphs above in which l2 is 4, In some variations of formula (12) described in the paragraphs above in which l2 is 4, each of Rai,Rbj, Ra2, jj2, as, i,3. A4, and Rb4 is H. In some variations of formula (12) described in the paragraphs above in which l2 is 4, each of Rai,Rbi, R^, Rb2, R33, R¾3, RA4, and M is CH3. In some variations of formula (12) described in the paragraphs above in which l2 is 4, each of Rai, ex, Ra2, R¾2, A , and Rb3 is H and each of A4 and b4 is CH3. In some variations of formula (12) described in the paragraphs above in which l2 is 4, each of Rai, M, Ra2, and Rb2 is H and each of Ra3, ¾3, Ra ; and ^ is CH3. In some variations of formula (12) described in the paragraphs above in which l2 is 4, each of Rai, R*i, Ra2, R*2, A3, and Rb3 is CH3 and each of Ra and Rb4 is H.
[295] In some variations of formula (12) described in the paragraphs above in which l2 is 4, each of Rai,Ra2, and A3 is H and each of Rj,i, ¾2, and B3 is CH3. In some variations of formula (12) described in the paragraphs above in which l2 is 4, Rai is H, Rbi i s CH3, and each of Ra2, ¾2, Ra3. and Rb3 is CH3. In some variations of formula (12) described in the paragraphs above in which l2 is 4, Rai is H, R1(i is CH3, and each of ^, R¾2, 33, and R¾3 is H. In some variations of formula ( 12) described in the paragraphs above in which h is 4, each of Rai and Ra2 is H, each of w and Rb2 is CH3, and each of as and R|>3 is H. In some variations of formula (12) described in the paragraphs above in which l2 is 4, each of Rai and a? is H, each of Rbi and Rb2 is CH3, and each of Ra3 and Rb3 is CH3.
[296] In some variations of formula (12) described in the paragraphs above in which /? is 4, Rai and Rbi are H, ^ and Rb2 are H, Ra3 and Rw are H, and Ra4 and Rb4 are "¾ . In some variations of formula (12) described in the paragraphs above which l2 i s 4, ai and R i are H,
R¾2 and R¾2 are H, Ra3 and ¾3 are CH3, and RA4 and M are
Figure imgf000100_0001
. In some variations of formula (12) described in the paragraphs above in which l2 is 4, Ra! and ¾i are H, Ra2 and are CH3, Ras and ¾ are O . and Ra4 and R¾4 are "^- . In some variations of formula (12) described in the paragraphs above in which l2 is 4, Rai and i are CH3, a2 and ¾2 are CH3,
Ra3 and ¾3 are CH3, and Ra4 and R¾4 are '¾ ,
[297] In some variations of formula (12) described in the paragraphs above in which /? is 4, Rai and bi are H, ^ and Rb2 are H, Ra3 and Rw are "^- and Ra4 and Rj,4 are ^ . In some variations of formula ( 12) described in the paragraphs above in which /? is 4, ai and RM are H,
RA2 and b2 are CH3, Ra3 and b3 are
Figure imgf000100_0002
. In some variations of formula (1 2) described in the paragraphs above in which l2 i s 4, Raj and Rbi are CH3, Ra2 and
Rb2 are CH3, Ra3 and ¾3 are ^ , and Ra4 and RM are " L . In some variations of formula (12) described in the paragraphs above in which l2 is 4, Rai is H, RM is CH3, Ra2 and Rj>2 are
CH3, A3 and R&j are ^\ and Ra4 and I¾4 are "^- . In some variations of formula (12) described in the paragraphs above in which l2 is 4, Rai is H, R¾i is CH3, R^ is H, ¾2 is CH3, Ra3
Figure imgf000100_0003
and Rj,3 are .
[298] In some variations of formula (12) described in the paragraphs above in which /? is 4, Rai and Rbi are H, R^ and Rb2 are " V¾Si RA3 and Rb3 are ' V¾-%£ and Ra4 and RM are ' V¾ Si . In some variations of formula (12) described in the paragraphs above in which l2 is 4, Raj and Rbi are CH3, Ra2 and b2 are " V¾Si Ra and Rb are Hi and Ra and Rb4 are S ^£\ In some variations of formula (1 2) described in the paragraphs above in which l2 i s 4, Rai is H, RM i s
Figure imgf000100_0004
CH3, Ra2 and 2 are , In some variations of formula (12) described in the paragraphs above in which l2 is 4, Ra! and ¾ι an
Figure imgf000100_0005
< R„-> and RLi a arree » Ra3, a anndd a arree "'^¾- ^ and Ra4 and RM are 9] In some variations of formula (12) described in the paragraphs above in which l2 is 4, Rai p
and ¾i are H, Ra2 and ¾2 are H, Ra3 and ¾3 are H, and Ra4 and I¾ are ¼ "*A· . In some variations of formula (12) described in the paragraphs above in which l2 is 4, Rai and R¾i are H,
O
Ra2 and RB2 are H, Ra3 and j,3 are CH3, and Ra4 and RI I are "^- . In some variations of formula (12) described in the paragraphs above in which l2 is 4, Ra! and j,j are H, R^ and Rb2
O
are CH3, R^ and ¾3 are CH3, and Ra-i an RM are · ^\ In some variations of formula ( 12) described in the paragraphs above in which l2 is 4, Rai and w are CH3, Ra2 and ¾ are CH3,
O
A3 and ¾3 are CH3, and A4 and R&4 are ¾A .
[300] In some variations of formula (12) described in the paragraphs above in which l2 is 4, Rai
O
and Rbi are H, Ra2 and i,2 are H, Ra3 and ¾>3 are · , and Ra4 and Rb4 are v. In some variations of formula (12) described in the paragraphs above in which l2 is 4, ai and R i are H,
O O
Ra2 and (,2 are CH3, Ra3 and Rb3 are % A and A4 and &4 are % A ^\ In some variations of formula (12) described in the paragraphs above in which l2 is 4, ai and R i are CH3, Ra2 and
O O
Rb2 are CH3, Ra3 and Rb3 are · and A4 and RM are ^\ In some variations of formula (12) described in the paragraphs above in which /? is 4, Rai is H, ¾i is C¾, Ra2 and ¾2 are
O p
CH3, Ra3 and Rj,3 are % '¾A , and Ra4 and I¾4 are % ^ \ In some variations of formula (12) described in the paragraphs above in which !? is 4, RaJ is H, R¾i is C¾, Ra2 is H, ¾2 is CH3, A3 o o
and Rba are ¼ '^- ^\ and RA and M are ¼ ' *· ^ί\
[301] In some variations of formula (12) described in the paragraphs above in which l2 is 4, RaJ and i»i are H, Ra2
Figure imgf000101_0001
In some variations of formula (12) described in the paragraphs above in which l2 is 4, ai and ¾i are
0 0 o
CH3, Ra2 and ¾2 are ¾A ^\ Ra3 and ¾3 are A ** , and Ra4 and Rb4 are A ¾ . In some variations of formula (12) described in the paragraphs above in which l2 is 4, ai is H, Rbi is
0 0 o
O . Rai and ¾2 areA Ra3 and Rb3 are ¾ i and Ra4 and RM are Α In some variations
O
of tormula (12) described in the paragraphs above in which l2 is 4, Rai and M are - A2 and Rb2 are
Figure imgf000102_0001
.
[302] In some variations of formula (12) described in the paragraphs above in which l2 is 4, Ras — y O and RM are "^- ^*, A2 and ^ are H, and R1(3 are H, and RA4 and t,4 are *"¾· In some variations of formula (12) described in the paragraphs above in which l2 is 4, Ra! and w are
O
"¾ Ra2 and R¾2 are CH3, and RM are CH3, and 34 and ¾4 are f\ In some variations ot formula (12) described in the paragraphs above in which l2 is 4, RaJ and RbJ are '¾ , Ra2
O
and Rj,2 are H, Ra3 and j,3 are CH3, and RA4 a d Rj>4 are ¾ ' 1A ^ ,
[303] In some variations of formula (12) described in the paragraphs above in which l2 is 4, Raj
' ~7 S~~~7 O
and Rbi are ^ Ra2 and Rj,2 are "Q Ra3 and R1(3 are H, and Ra4 and Rb4 are A· In some variations of formula (12) described in the paragraphs above in which l2 is 4, Ral and M are " .¾ - , Ra2 and RB2 are
Figure imgf000102_0002
In some variations of formula ( 12) described in the paragraphs above in which l2 is 4, ai and ¾i are
Figure imgf000102_0003
. In some variations of formula (12) described in the paragraphs above in which l2 is 4, Rai and Rbi are
" ¾¾ , Ra2 and Rh2 are " ¾ , Ra3 and j,3 are H, and Ra4 and M are
Figure imgf000102_0004
.
[304] In some variations of formula (12) described in the paragraphs above in which /? is 4, Rai and RM are
Figure imgf000102_0005
5] In some variations of formula (12) described in the paragraphs above in which l2 is 4, Rai
Ό
and ¾i are ^\ Ra2 and Rb2 are '¾ r \ Ra3 and Rb3 are H, and Ra4 and Rb are f\ In some vari ations of formula (12) described in the paragraphs above in which /_? is 4, Rai and bi are vv , Ra2 and Rb2 are
Figure imgf000103_0001
In some variations of formula (12) described in the paragraphs above in which l2 is 4, Rai and Rb! are
Figure imgf000103_0002
Ra2 and Rb2 are In some variations of formula (12) described in the paragraphs above in which 12 is 4, Ra! and Rb! are
■r O O
¾A ¾A
"¾ a2 and Rb2 are '¾· a3 and R 3 are H, and Ra4 and R 4 are < \
[306] In some variations of formula (12) described in the paragraphs above in which l2 is 4, Rai
Figure imgf000103_0003
[307] In some variations of formula (12) described in the paragraphs above in which /? is 4, Rai and Rb{ are
Figure imgf000103_0004
In some variations of formula (12) described in the paragraphs above in which l2 is 4, Rai and R¾i are
Figure imgf000103_0005
In some vari ations of formula (12) described in the paragraphs above in which I? is 4, Rai and bi are
Figure imgf000103_0006
In some vari ations of formula (12) described in the paragraphs above in which !2 is 4, Ral and RM are
Figure imgf000103_0007
[308] In some variations of formula (12) described in the paragraphs above in which l2 is 4, as and Rbl are
Figure imgf000103_0008
, 9] In some variations of formula (12) described in the paragraphs above in which l2 is 4, Rai and ¾i are H, Ra2 and Rj>2 are H, and Ras and & and Ra4 and Rt>4 together are '¾ . In some variations of formula (12) described in the paragraphs above in which l2 is 4, Ral and RbJ are II, and R 2 are CH3, and Ra3 and Rb3 and a and RM together are " <~ V in some variations of formula (12) described in the paragraphs above in which l2 is 4, aj and Ra2 are H, i and j,2 are Cl¾, and as and b3 and a4 and ¾4 together are x .
[310] In some variations of formula (12) described in the paragraphs above in which l2 is 4, Rai and j,i are H, and ^ are
Figure imgf000104_0001
and Ra3 and b3 and a and Rb together are '^- , In some variations of formula (12) described in the paragraphs above in which l2 is 4, Rai and Rbi
Figure imgf000104_0002
, Ra2 and *,? are CH3, and a3 and 3 and a4 and b4 together are - . In some variations of formula (12) described in the paragraphs above in which l2 is 4, Rai is H, R¾i is
Figure imgf000104_0003
CI¾, Ra2 and R 2 are " N^
[311] In some variations of formula (12) described in the paragraphs above in which l2 is 4, Rai and Rbi are H, and 2 are
Figure imgf000104_0004
and Ra3 and ¾3 and Ra4 and Rb4 together are . In some variations of formula (12) described in the paragraphs above in which l2 is 4, ai and Rbi O
are ' <■ ¾ , a2 and ¾2 are CH3, and a3 and Rj,3 and Ra4 and b4 together are ' <· . In some variations of formula (12) described in the paragraphs above in which l2 is 4, Rai is H, i is
O
¾A
CH3, Ra2 and b2 are and Ra3 and Rb3 and Ra4 and b4 together are y Y
[312] In some variations of formula (12) described in the paragraphs above in which l2 is 4, Rai
O O
and i are ¾ A / a2 and b2 are '¾·^f and ^ and ? and Ra4 and 4 together are ""^ Y In some vari ations of formula (12) described in the paragraphs above in whi ch /? is 4, Rai and bi are
Figure imgf000104_0005
and Ra3 and R¾3 and Ra4 and R¾4 together are 1 . In some variations of formula (12) described in the paragraphs above in which /? is 4, Rai and Rbi are
Figure imgf000105_0001
and A3 and B3 and RA4 and Rb4 together are ¾ .
[313] In some variations of formula (12) described in the paragraphs above in which h is 4, Ral and R[»i are " Ra2 and Rb2 are and a3 and ¾3 and 34 and Rb4 together are
[314] In some variations of formula (12) described in the paragraphs above in which l2 is 4, Raj and M and Ra2 and 2 together are - and ^ and bj and A4 and RB4 together are
[315] In some variations of formula (12) described in the paragraphs above in which oj is 1, Rai and i are both H. In some variations of formula (12) described in the paragraphs above in which 0[ is 1, Raj is H and Rb! is CH3. In some variations of formula (12) described in the paragraphs above in whi ch o} i s 1, Rai and R¾i are both CH3. In some variations of formula (12) described in the paragraphs above in which o is 1, Rai and bi are "¾ . In some variations of formula (12) described in the paragraphs above in which o1 is 1, Rai and ϊ½ are
Figure imgf000105_0002
[316] In variations of formula (12) described in the paragraphs above in which oj is 2, the two instances of Ra and Rb are indicated as Ral and Rbl and a2 and Ι½, respectively. In some variations of formula (12) described in the paragraphs above in which o} is 2, each of Rai and Rbi and a2 and 2 i s H. In some variations of formula (12) described in the paragraphs above in which oi is 2, each of Rai and bi and a2 and R 2 is CH3. In some variations of formula (12) described in the paragraphs above in which oj is 2, each of Rai and Ra2 is H and each of Rbl and Rj,? is CH3. In some variations of formula ( 12) described in the paragraphs above in which o} is 2, each of Rai, Ra2, and Rbi i s H and Rb2 is CH3.
[317] In some variations of formula (12) described in the paragraphs above in which o} is 2,
Figure imgf000105_0003
each of Rai and Rbi is H and . In some variations of formula (12) described in the paragraphs above in which oj is 2, each of Ra{ and Rb) is H and Ra2 and R 2 are O
^ . In some variations ot formula (12) described in the paragraphs above in which o} is 2, each ot ai and RM is C¾ and and R 2 are "¾ ^*- . In some variations of tormula (12) described in the paragraphs above in which o} is 2, each of Rai and i is CH3 and Ra? and Rj>2
Figure imgf000106_0001
are
In some variations of formula (12) descri bed in the paragraphs above in which oi is 2, Rai is H,
Rbi is CH3, and Ra2 and ¾ are "^- . In some variations of formula (12) described in the
O
paragraphs above in which o} is 2, Ra! is H, Rbi is CH3, and Ra2 and j,? are Ά . In some variations of formula (12) described in the paragraphs above in which o} is 2, Rai and RM and
Ra2 and j,2 together are '^- V In some variations of formula ( 12) described in the paragraphs above in which o i s 2, ai and R i are '^- ^ Ra2 and R 2 are "^- ^\ In some variations of formula (12) described in the paragraphs above in which oj is 2, ai and i are '¾· Ra2 and
O
Rb? are ^ . In some variations of formula (12) described in the paragraphs above in which o}
O O
is 2, Rai and R1(i are R^ and R¾2 are .
[318] In variations of formula ( 12) described in the paragraphs above in which o} is 3, the three instances of Ra and ¾ are indicated as ai and Rbi; a2 and ¾2; and A3 and Κ¾3, respectively. In some variations of formula (12) described in the paragraphs above in which o is 3, In some variations of formula (12) described in the paragraphs above in which oj is 3, each of Rai,Rt>i, ¾2, 2, a3, and bs s H. In some variations of formula (12) described in the paragraphs above in which oj is 3, each of Rai,Rbi, Ra2, ¾>2, Ra3, and b.? is C¾. In some variations of formula ( 12) described in the paragraphs above in which oi i s 3, each of Rai,Rbi, ¾2, and Rj)2, i s H and each of Ra3 and bj is CH3. In some variations of formula (12) described in the paragraphs above in which oj i s 3, each of Rai,Rbi, ¾2, and Rj,2, is CH3 and each of aj and ¾3 is H. In some variations of formula (12) described in the paragraphs above in which oj is 3, ai is H and each of Ra2, RA3, Rbi, ¾2, and Rbj i CH3. In some variations of formula (12) described in the paragraphs above in which o is 3, each of Rai and Ra2 is H and each of R^. Rbi, M, and R^s is CH3. In some variations of formula (12) described in the paragraphs above in which oi is 3, each of Rai, Ra2, and RA3 is H and each of M, ¾, and b3 is
[319] In some variations of formula (12) described in the paragraphs above in which o is 3, each of Rai,Rbi, Ra2, and ¾2, Ϊ8 H and a3 and ¾3 are "¾ . In some variations of formula (12) described in the paragraphs above in which o} is 3, each of Rai,Rbi, Ra2, and Rb2, is CH3 and R¾3 an
Figure imgf000107_0001
variations of formula (12) described in the paragraphs above in which oi is 3, Rai is H and each of Ra2, Rbi, and Rj,2 is CH3, and A3 and 3 are "x . In some variations of formula (12) described in the paragraphs above in which o/ is 3, each of Rai and
Ra2 is H and each of w and (,2 is CH3, and as and b3 are
Figure imgf000107_0002
[320] In some variations of formula (12) described in the paragraphs above in which oi is 3,
O
each of Rai,Rbi, Ra2, and Rb2, is H and a3 and R^ are . In some variations of formula ( 12) described in the paragraphs above in which o} is 3, each of R3I,RM, Ra2, and ¾2, is CH3 and aj
O
and j,3 are '^- *" . In some variations of formula (12) described in the paragraphs above in which
O
oj is 3, Ra{ is H and each of ^, bi, and Rj,2 is CH3, and ^ and j,3 are <- 5 . In some variations of formula (12) described in the paragraphs above in which oi is 3, each of Rai and
O
Ra2 is H and each of M and b2 is CH3, and aj and Rb3 are .
[321] In some variations of formula (12) described in the paragraphs above in which oj is 3, Rai and R¾i are
Figure imgf000107_0003
, Ra2 and Rs,2 are "¾ and each of Ra3 and Rj,3 is H. In some variations of formula (12) described in the paragraphs above in which o} is 3, Rai and R¾i are "^- Ra2 and j,2 are " ^ , and each of Ras and B3 is CH3. In some variations of formula (12) described in the paragraphs above in which o} is 3, Ral and Rw are "¾ , Ra2 and Rb2 are '^- , Ra3 is H, and bs is CH3. In some variations of formula (12) described in the paragraphs above in which O] is 3, Ral and bi are , Ra2 and Rb2 are "^- ^ , and each of Ra3 and R^ is H. In some variations of formula (12) described in the paragraphs above in which oj is 3, Ral and Rbi
Figure imgf000108_0001
, Ra2 and Rb2 are s CH3. In some variations of formula
(12) described in the paragraphs above in which o is 3, Rai and bi are "¾ ^ and R 2 are
Figure imgf000108_0002
[322 ] In some variations of formula (12) described in the paragraphs above in which o} is 3, Raj and R j are "¾ Ra2 and Rb2 are "¾· ? and each of ¾.? and Rb3 is H. In some variations of formula (12) described in the paragraphs above in which oj is 3, Ra} and R j are "^- , Ka2
Figure imgf000108_0003
Rb3 is CH3. In some variations of formula (12) described
— 7 O
\ . ¾^· in the paragraphs above in which oj is 3, Raj and bj are "¾ Ra2 and Rb2 are '^- Ra3 is H, and Rbs is CH3. In some variations of formula (12) described in the paragraphs above in which o}
is 3, Rai and R¾i are " , Ra2 and R 2 are and each of a3 and 3 is H. In some variations of formula (12) described in the paragraphs above in which o} is 3, Raj and j,t are
O
^
'¾ and Rb2 are · ^1*, and each of Ra3 and Rb3 is CH3. In some variations of formula
(12) described in the paragraphs above in which O] is 3, Ral and R i are ^ Ha2 and Rb2 are O
-\ Ra3 is H, and Rb3 is CH3.
[323] In some variations of formula (12) described in the paragraphs above in which o is 3,
O O
Rai and i are 0 '¾·- Ra2 and Rb2 are 0 '^-0 <* and each of R^ and Rb3 i s H. in some variations of
O
formula (12) described in the paragraphs above in which } is 3, aj and bi are '¾· Ra2 and O
¾2 are ' *· and each of Ras and Rj>3 is CH3. In some variations of formula (12) described in
O O
the paragraphs above in which oj is 3, Rai and ¾i are "*· ΆΆ2 and R¾2 are RA3 is H, and fcj is CH3. In some variations of formula (12) described in the paragraphs above in which o}
O p
is 3, Rai and R¾i are Ra2 and Rj,2 are and each of and Rb3 is II. In some variations of formula (12) described in the paragraphs above in which o} is 3, Ra{ and Rj,t are O O
'¾ f\ Ra2 and j,2 are ' *· and each of Ras and ¾3 is CH3. In some variations of formula (12)
O O
described in the paragraphs above in which o} is 3, Raj and are Ra2 and Rj,2 are
Figure imgf000109_0001
[324] In some variations of formula (12) described in the paragraphs above in which oj is 3,
Raj and RM and a2 and ¾2 together are '^- and each of A3 and R&s is H. In some variations of formula (12) described in the paragraphs above in which 01 is 3, Rai and j,i and
Ra2 and ¾2 together are " , and each of as and is CH3. In some variations of formula (12) described in the paragraphs above in which o} is 3, Rai and J¾,i and Ra2 and ¾2 together are , a3 is H, and j,3 is CH3. In some variations of formula (12) described in the paragraphs above in which o} is 3, Ra! and &j and Ra2 and R¾2 together are and A and j,3 are
In some variations of formula (12) described in the paragraphs above in which o} is 3,
Rai and R¾i and Ra2 and i,2 together are
Figure imgf000109_0002
.
[325] In variations of formula (12) described in the paragraphs above in which o} is 4, the three instances of Ra and Rj, are indicated as Rai and j,i; Ra2 and ¾2; Ra3 and ^; and A4 and Rj>4, respectively. In some variations of formula (12) described in the paragraphs above in which o} is 4, In some variations of formula (12) described in the paragraphs above in which oj is 4, each of Rai,Rbi, Ra2, Rb2, Ra3, ¾3, ¾4, and RB4 is H, In some variations of formula ( 12) described in the paragraphs above in which 01 is 4, each of Rai,Rt>i, Ra2, Rt>2, a3, ¾3. Ra4, and R¾ is CH3. In some vari ations of formula (12) described in the paragraphs above in which o} is 4, each of Rai, Rbi, Ra2, b2, a3, and R¾3 is H and each of RA4 and M is CH3. In some variations of formula (12) described in the paragraphs above in which oi i s 4, each of Rai, R^, Ra2, and Ι½ i s H and each of Ra3, j,3> Ra4. and ^ is CH3. In some variations of formula (12) described in the paragraphs above in which oi is 4, each of Rai, Rt>i, Ra2, R¾2, Ra3, and 1(3 is CH3 and each of
Figure imgf000110_0001
In some variations of formula (12) described in the paragraphs above in which o} is 4, each of Rai,Ra2, and Ra3 is H and each of ¾i, 1½, and Rb3 is CH3. In some variations of formula (12) described in the paragraphs above in which Oj is 4, Ral is H, j,} is CH3, and each of Ra2, ¾2, Ra3, and Rj,3 is CH3. In some variations of formula (12) described in the paragraphs above in which oi is 4, ai is H, j,i is CH3, and each of Ra2, &2, a3, and Rj,3 is H. In some variations of formula (12) described in the paragraphs above in which oi is 4, each of Rai and Ra2 is H, each of M and R¾2 is CH3, and each of ^ and Rj,3 is H. In some variations of formula ( 12) described in the paragraphs above in which oj is 4, each of Rai and R^ is H, each of R^i and j,2 is CH3, and each of as and ¾3 is ('! .
[327] In some variati ons of formul a (12) described in the paragraphs above in which oj is 4,
Rai and RM are H, Ra2 and Rb2 are H, ^ and j,3 are H, and Ra4 and R¾4 are '¾ . In some variations of formula (12) described in the paragraphs above in which o,- is 4, ai and j>i are H,
Ra2 and j,2 are H, RA3 and RB3 are CH3, and R^ and B4 are "¾· , In some variations of formula (12) described in the paragraphs above in which oj is 4, Raj and Rj,i are H, Ra2 and Rb2 are CH3, Ra3 and B3 are CH3, and A4 and B4 are '^- *" . In some variations of formula (12) described in the paragraphs above in whic > is 4, Rai and bi are CH3, Ra2 and Rb2 are CH3,
Ra3 and B3 are CH3, and Ra4 and R1(4 are
Figure imgf000110_0002
[328] In some variations of formula (12) described in the paragraphs above in which O i is 4,
Rai and Rbi are H, Ra2 and b2 are H, Ra3 and b3 are "^- ^\ and Ra4 and Rb4 are "^- . In some vari ations of formula (12) described in the paragraphs above in which o} is 4, RaS and R¾i are H, 32 and Rb2 are CH3, Ra3 and Rb3 are "¾ and Ra4 and Rb4 are '¾ . In some variations of formula (12) described in the paragraphs above in which 0,- is 4, Ral and bi are
H3, a2 and ¾2 are CH3, Ra3 and R 3 are
Figure imgf000110_0003
In some variations of formula (12) described in the paragraphs above in which oj is 4, Rai is H, ¾i is CH3, Ra2 and
Rb2 are CH3, R¾3 and ¾j are
Figure imgf000111_0001
. In some variations of formula (12) described in the paragraphs above in which oj is 4, Raj is H, RM is CH3, R¾2 is H, ¾2 is
Figure imgf000111_0002
CH3, RA3 and ¾3 are [329] In some variati ons of formula (12) described in the paragraphs above in which oj is 4,
Ra3 and RM are H, Ra2 and Rb2 are " W Ra3 and Rb3 are '¾ Hi , and Ra4 and j,4 are "¾ S 5£ . In some variations of formula (12) described in the paragraphs above in which oi is 4, Rai and R|>i S VS£
are CH3, ^ and R|>2 are '¾ Ras and ¾3 are "^- and Ra4 and ^ are ^\ In some variations of formula (12) described in the paragraphs above in which o is 4, RaJ is H, RM is
CH3, Ra2 and ¾2 are W" , Ra3 and &3 are '¾ £ and Ra4 and RM are S ^i . In some variations of formula (12) described in the paragraphs above in which o; is 4, Rai and RM are
, a2 and R¾2 are Si Ra3 and ¾3 are Si and Ra4 and R*»4 are
Figure imgf000111_0003
[330] In some variations of formula (12) described in the paragraphs above in which o i is 4,
O
Rai and Rw are H, Ra2 and Kb2 are H, R^ and Rb3 are H, and Ra4 and j,4 are ¾ . In some variations of formula (12) described in the paragraphs above in which oj is 4, Rai and ^ are H,
O
Ra2 and Rb2 are H, Ra3 and R(,3 are CH3, and Ra4 and ¾4 are '¾· ^\ In some variations of formula (12) described in the paragraphs above in which o} is 4, Rai and Rbi are H, a2 and R¾2
O
are CH3, Ra3 and Rb3 are CH3, and Ra4 and ¾4 are ¾ '¾·% In some variations of formula (12) described in the paragraphs above in which o} is 4, RaS and R¾i are CH3, Ra2 and R1(2 are CH3,
O
Ra3 and Rj,3 are CH3, and Ra4 and M are "^- ^ .
[331] In some variations of formula (12) described in the paragraphs above in which o} is 4,
O
Rai and j,i are H, Ra2 and R|>2 are H, Ra3 and Rb3 are ^ and Ra4 and R are v. In some variations of formula (12) described in the paragraphs above in which o is 4, RaJ and Rbj are H, Ra2 and R¾2 are CH3, A3 and ¾3 are
Figure imgf000112_0001
In some variations of formula (12) described in the paragraphs above in which oj is 4, Rai and Rbi are CH3, a2 and o o
Rb2 are CH3, RA3 and ¾3 are '¾· * and A4 and ΜΜ are '¾· #\ In some variations of tormula (12) described in the paragraphs above in which Oj is 4, Rai is H, is CH3, Ra2 and Ι¾2 are
CH3, A3 and ¾3 are
Figure imgf000112_0002
In some variations of formula (12) described in the paragraphs above in which oj is 4, Rai is H, Rbi is CH3, Ra2 is H, j,2 is CH3,
Figure imgf000112_0003
Ra3 an Rw are an Ra4 an RM are
[332] In some variations of formula (12) described in the paragraphs above in which oj is 4,
Figure imgf000112_0004
In some vari ations of formula (12) described in the paragraphs above in which o/ is 4, Ra3 and M
0 0 o
are CH3, and j,2 are ¾ '¾A· <j Ra3 and Ri>3 are ¾ '^A- and Ra4 and R|>4 are ¾ LA ^ , In some variations of formula (12) described in the paragraphs above in which ο,· is 4, Rai is H, j,} is
Figure imgf000112_0005
In some variations
0 of formula (12) described in the paragraphs above in which o} is 4, Rai and Rbi are % "*A· Ra2 and
Figure imgf000112_0006
[333] In some variations of formula (12) described in the paragraphs above in which oj is 4, y ¾A
Raj and Rbi are Ra2 and (,2 are H, Ra3 and Rb3 are H, and Ra4 and &4 are '¾· ^ . In some variations of formula (12) described in the paragraphs above in which oi is 4, Rai and R|>i —j o
are ^\ Ra2 and j>2 are CH3, Ra3 and Rb3 are CH3, and Ra4 and Rt>4 are ¾ '^A- In some variations of formula (12) described in the paragraphs above in which oj is 4, Ral and Rbi are
Figure imgf000112_0007
.
I l l [334] In some variations of formula (12) described in the paragraphs above in which oi is 4,
Riii and M are Ra2 and R^i are "% ¾3 and Rb3 are H, and Ra4 and Rj,4 are '^- <*\ In some variations of formula (12) described in the paragraphs above in which o} is 4, RaS and R¾i
Figure imgf000113_0001
In some variations of formula (12) described in the paragraphs above in which o; is 4, Rai and j,i are
Figure imgf000113_0002
'¾ a2 and j,2 are ' *· ^* . In some variations of formula (12) described in the paragraphs above in which ο,- is 4, ai and M are
O
"¾ , a2 and R¾2 are , aj and ¾3 are H, and Ra4 and are '¾· .
[335] In some variations of formula (12) described in the paragraphs above in which o i is 4,
Rai and RM are NC Ra2 and Rj,2 are N ^i , Ra3 and Ι¾,3 are % and Ra4 and Rb4 are
O
[336] In some variations of formula (12) described in the paragraphs above in which oi is 4,
O O
Rai and Rbi are "¾ Ra2 and are Ra3 and j>3 are H, and Ra4 and Rb4 are ^ . In some variations of formula ( 12) described in the paragraphs above in which o} is 4, ai and j,i
O O
are " ^ , Ra2 and ϊ½ are '^- ^ and b3 are CH3, and Ra4 and Rb4 are ^\ In some variations of formula (12) described in the paragraphs above in which o; is 4, Rai and M are
"¾ G , Ra2 and R 2 aie
Figure imgf000113_0003
In some variations of formula (12) described in the paragraphs above in which oi is 4, as and i are
O O
"¾ Ra2 and Rb2 are % · Ra3 and Rb3 are H, and Ra4 and R 4 are % A· ^ , [337] In some variations of formula (12) described in the paragraphs above in which oi is 4,
Riii and R i are
Figure imgf000114_0001
and Rb4 are
O
[338] In some variations of formula (12) described in the paragraphs above in which O i is 4,
Rai and Rbi are
Figure imgf000114_0002
. In some variations of formula (12) described in the paragraphs above in which oj is 4, Rai and R i are
Figure imgf000114_0003
variations of formula (12) described in the paragraphs above in which o; is 4, Rai and bi are 0 0 o
A A A
'¾· <* a2 and Rb2 are "¾ Ra3 and Rb3 are CH3, and Ra4 and Rb4 are ^ . In some variations of formula (12) described in the paragraphs above in which o; is 4, Rai and bi are 0 0 o
¼· Ra2 and Rb2 are ½ Ra3 and Rb3 are H, and Ra4 and Rb4 are
[339] In some variations of formula (12) described in the paragraphs above in which o/ is 4,
Figure imgf000114_0004
[340] In some variations of formula (12) described in the paragraphs above in which o> is 4,
Ra3 and Rb3 are H, Ra2 and Rb2 are H, and Ra3 and Rb3 and Ra4 and Rb4 together are . In some variations of formula (12) described in the paragraphs above in which o, is 4, Rai and R i are H, R^ and Rb2 are CH3, and Ra3 and Rj,3 and Ra4 and Rb4 together are ' L . In some variations of formula (12) described in the paragraphs above in which oj is 4, Ral and Ra2 are H,
Rbi and Rb2 are CH3, and and Rb3 and Ra4 and Rb4 together are [341] In some variations of formula (12) described in the paragraphs above in which o> is 4,
Raj and j are H, Ra2 and R 2 are '¾ and a3 and 3 and Ra4 and R 4 together are . In some variations of formula (12) described in the paragraphs above in which o} is 4, Rai and Rbj are " Ra2 and Rb2 are CH3, and Ra3 and Rb3 and Ra4 and Rb4 together are ' ¾ . In some variations of formula (12) described in the paragraphs above in which o} is 4,
Ra3 is H, RbJ is CI¾, Ra2 and Rb2 are '¾ , and Ra3 and Rb3 and Ra4 and Rb together are
[342] In some variations of formula (12) described in the paragraphs above in which o > is 4,
O
Rai and R¾i are H, Ra2 and R 2 are and Ra3 and R 3 and Ra4 and Rb4 together are ^
In some variations of formula (12) described in the paragraphs above in which oi is 4, Ra! and
9
j,i are "*· Ra2 and R 2 are CH3, and a3 and R 3 and Ra4 and R 4 together are ¾ V In some variations of formula (12) described in the paragraphs above in which oi is 4, Rai is H, R i is CH3, Ra2 and Rb2 are
Figure imgf000115_0001
and Ra3 and Rb3 and Ra4 and Rb4 together are ¾ V
[343] In some variations of formula (12) described in the paragraphs above in which oi is 4, and Rb3 and Ra4 and R 4 together
Figure imgf000115_0002
In some variations of formula (12) described in the paragraphs above in which o > is 4, and Ri,i are
Figure imgf000115_0003
Ra2 and Rb2 are and a3 and R 3 and Ra4 and Rb4 together are . In some variations of formula (12) described in the paragraphs above in which o i is 4,
O O
% A/ A
Rai and Rb3 are '¾· Ra2 and Rb2 are - **, and ^ and Rb3 and Ra and Rb together are
[344] In some variations of formula (12) described in the paragraphs above in which oj is 4,
Rai and Rbj are "¾ Ra2 and Rb2 are
Figure imgf000115_0004
and Ra3 and Rb3 and Ra4 and Rb4 together are [345] In some variations of formula (12) described in the paragraphs above in which o i is 4, Riii and ¾i and Ra2 and Rj>2 together are "¾ and R¾3 and b3 and Ra4 and ^ together are
[346] In some variations of formula (12) described in the paragraphs above in which o2 is 1, Raj and M are both H. In some variations of formula (12) described in the paragraphs above in which Oi is 1, Rai is H and ^i is CH3. In some variations of formula (12) described in the paragraphs above in which o2 is 1, Raj and ¾j are both CH3. In some variations of formula (12) described in the paragraphs above in which o? is 1 , ai and RM are
Figure imgf000116_0001
. In some variations of
O
formula (12) described in the paragraphs above in which o2 is 1, Rai and j)i are * ,
[347 ] In variations of formula (12) described in the paragraphs above in which o2 is 2, the two instances of Ra and Rb are indicated as Rai and j,i and a2 and Rb2, respectively. In some variations of formula (12) described in the paragraphs above in which o2 is 2, each of Rai and j,i and a2 and &2 is H. In some variations of formula (12) described in the paragraphs above in which o2 i s 2, each of Rai and RM and Ra2 and Rb2 is CH3. In some variations of formula (12) described in the paragraphs above in which o2 is 2, each of Rai and Ra2 is H and each of Rbi and Rb2 is CH3. In some variations of formula (12) described in the paragraphs above in which o2 is 2, each of Rai, Ra2, and j>i is H and Rb2 is (Ί .
[348] In some variations of formula (12) described in the paragraphs above in which o2 is 2, each of RaJ and j,t is H and Ra2 and ¾2 are '¾ ^ . In some variations of formula (12) described in the paragraphs above in which o2 is 2, each of Rai and ϊ½ is H and Ra2 and j,2 n O
'¾· . In some variations oi formula (12) described in the paragraphs above in which o2 is 2, each of ai and M is CH3 and Ra2 and j,2 are '¾ . In some variations of formula (12) described in the paragraphs above in which o2 is 2, each of Rai and j,i is CH3 and Ra2 and j,2
Figure imgf000116_0002
are In some variations of formula (12) described in the paragraphs above in which o2 is 2, ai is H
Rex is CH3, and Ra2 and ¾2 are '¾ ^ . In some variations of formula (12) described in the
O
paragraphs above in which o2 is 2, ai is H, M is CH3, and Ra2 and Rb2 are "*· . In some variations of formula (12) described in the paragraphs above in which o2 is 2, Rai and Rbi and and Rb2 together are . In some variations of formula (12) described in the paragraphs e in which o2 is 2, Rai and R1(i are "^- and R1(2 are "^- . In some variations of formula (12) described in the paragraphs above in which o2 is 2, Rai and i»i are "¾ Ra2 and p
Rb2 are ¼ "*·Α· ί · In some variations of formula (12) described in the paragraphs above in which o2
A - A
is 2, Ra3 and j,j are ^ Ra2 and ^ are
[349] In variations of formula (12) described in the paragraphs above in which o2 is 3, the three instances of Ra and j, are indicated as Raj and ^; Ra2 and Rb2; and as and ¾3, respectively. In some variations of formula (12) described in the paragraphs above in which o2 is 3, In some variations of formula (12) described in the paragraphs above in which o2 is 3, each of Rai,Rw, a2, Rb2, R 3, and Rb3 is H. In some variations of formula (12) described in the paragraphs above in which o2 is 3, each of Rai,Rbi, R_ , ¾2, RA3, a d &j is CH3. In some variations of formula (12) described in the paragraphs above in which o2 is 3, each of Rai,Rbi, R_ , and Rj>2, is H and each of aa and R^a is CH3. In some variations of formula (12) described in the paragraphs above in which o2 is 3, each of Rai,Rbi, Ra2, and ¾2, is CH3 and each of 33 and Rb3 is H. In some variations of formula ( 12) described in the paragraphs above in which o2 is 3, Rai is H and each of Ra2, RA3; Rbi, 2, and ^ is CH . In some variations of formula (12) described in the paragraphs above in which o2 is 3, each of Rai and Ra2 is H and each of R^ Rbi, R*2, and R 3 is CH3. In some variations of formula (12) described in the paragraphs above in which o? is 3, each of Rai, Ra2, and Ras is H and each of RM, Rj,2, and j,3 is CH3.
[350] In some variations of formula (12) described in the paragraphs above in which each of Rai,Rbi, Ra2, and Rb2, is H and A3 and Rj>3 are '¾ . In some variations of formula ( 12) described in the paragraphs above in which o2 is 3, each of Rai,Rs>i, Ra2, and Rj>2, is CH3 and Ras and Rj,3 are "^- . In some variations of formula (12) described in the paragraphs above in which (>2 is 3, Raj is H and each of Ra2, M, and ¾2 is CH3, and A3 and RM are "¾ . In some variations of formula (12) described in the paragraphs above in which o2 is 3, each of Rai and a2 is H and each of Rm and R|,2 is (
Figure imgf000118_0001
[351] In some variations of formula (12) described in the paragraphs above in which o2 is 3,
O
each of Rai,Rj,i, a2, and &2, is H and as and Rj,3 are ^\ In some variations of formula (12) described in the paragraphs above in which o2 is 3, each of ai,Ri>i, a2, and Rb2, is CH3 and
O
and j>3 are Ά '¾ In some variations of formula (12) described in the paragraphs above in which
O
θ2 is 3, at is H and each of R^, R¾i, and ¾2 is CH3, and and Rj>3 are ' *· . In some variations of formula (12) described in the paragraphs above in which o2 is 3, each of Rai and
O
Ra2 is II and each ot Rw and ^ is CH3, and a3 and Rb3 are '¾· .
[352] In some variations of formula (12) described in the paragraphs above in which o2 is 3, Rai and M are '¾- , Ra2 and
Figure imgf000118_0002
a e "x and each of Ras and Rb3 s H. In some variations of formula (12) described in the paragraphs above in which o2 is 3, ai and bi are "¾ Ra2 and Rj,2 e ^ and each of Ras and ^s s CH3. In some variations of formul (12) described in the paragraphs above in which o2 is 3, Rai and RM are "¾ Ra2 and j,2 are
Figure imgf000118_0003
Ra3 is
H, and bs is CH3. In some variations of formula (12) described in the paragraphs above in which o2 is 3, Raj and R^i are I, , Ra2 and Rb2 are SI, , and each of A3 and ^ is H. In some vari ations of formula (12) described in the paragraphs above in which o2 is 3, ai and R¾i are '¾ **, Ra2 and R^ are "¾ , and each of Ra3 and ¾3 ίδ CH3. In some variations ot formula (12) described in the paragraphs above in which o? is 3, Ral and M are "¾¾ , Ra2 and Rb2 are
^ , ¾3 is H, and Rb3 is CH3. [353] In some variations of formula (12) described in the paragraphs above in which o2 is 3,
Rai and i are "¾ Ra2 and Rb2 are "^- and each of ^ and ^s is H. In some variations of iormuia (12) described in the paragraphs above in which o2 is 3, Rai and R|>i are ' Ra2
O
and Rj,2 are '¾· and each of aj and ¾ is CH3. In some variations of formula (12) described
O
in the paragraphs above in which o2 is 3, Rai and R i are "¾ Ra2 and Rb2 are L *" , Ra3 i s H, and Rb3 is CH3. In some variations of formula (12) described in the paragraphs above in which o2
O
is 3, Rai and bi are " Ra2 and Rb2 are < , and each of a3 and Rb3 is H. In some variations of formula (12) described in the paragraphs above in which o2 is 3, Rai and Rbi are — O
"¾ , Ra2 and Rb2 are and each of a3 and b3 is CH3. In some variations of formula
(12) described in the paragraphs above in which o is 3, ai and Rbi are "¾ *" , ^ and Rb2 are
O
, ¾- f\ a3 is H, and Rb3 is CH3.
[354] In some variations of formula (12) described in the paragraphs above in which o2 is 3,
O O
Rai and bi are Ra2 and R 2 are ' L , and each of a3 and 3 is H. In some variations of
O
formula ( 12) described in the paragraphs above in which o2 is 3, Ral and bi are r\ Ra2 and
9
Rb2 are and each of Ra3 and b3 i CH3. In some variations of formula (12) described in
O O
the paragraphs above in which o2 is 3, Rai and Rw are "¾A· ^ and Rb2 are ¾ '¾A· Ra3 is H, and Rb3 is CH3. In some variations of formula (12) described in the paragraphs above in which o2 o o
is 3, Rai and R¾i are Ra2 and Rj,2 are ' L and each of Ras and 3 is H. In some variations of formula (12) described in the paragraphs above in which o2 is 3, ai and Rbi are o o
< , Ra2 and j,2 are and each of aj and ¾3 is CH3. In some variations of tormula (12)
O O
described in the paragraphs above in which o2 is 3, Rai and i are ' 1 Ra2 and 2 are '^- is H, and ^is CH
[355] In some variations of formula (12) described in the paragraphs above in which o2 is 3,
Rai and bi and Ra2 and Rj>2 together are "¾ , and each of Ra3 and Rb3is H. In some variations of formula (12) described in the paragraphs above in which o2 is 3, Rai and M and
Ra2 and ¾ together are ^1- and each of ¾3 and bsis CH3. In some variations of formula (12) described in the paragraphs above in which o2 is 3, Ra3 and Rbi and Ra2 and R¾,2 together are
^"τ^ ¾a3 jg J ] anc Ris3is CH3. In some variations of formula (12) described in the paragraphs above in which o2 is 3, Rai and R i and ^ and Rj,2 together are · and Ras and 3 are
" . In some variations of formula (12) described in the paragraphs above in which o2 is 3,
Figure imgf000120_0001
Rai and M and Ra2 and j,2 together are
[356] In variations of formula (12) described in the paragraphs above in which o2 is 4, the three instances of Ra and j, are indicated as Rai and Rbi; Ra2 and ¾2; A3 and ϊ¾3; and A4 and &4, respectively. In some variations of formula (12) described in the paragraphs above in which o2 is 4, In some variations of formula (12) described in the paragraphs above in which o2 is 4, each of Rai,R¾i, 2, ¾2, a3, Rb3, Ra , and ¾4 is H. In some variations of formula (12) described in the paragraphs above in which o2 is 4, each of Rai,Rbi, Ra2, R2, A3, Rb3, ¾ , and RM is CH3. In some variations of formula (12) described in the paragraphs above in which o2 is 4, each of Rai, R*i, ¾2, i>2, a3, andRb3is H and each of Ra4 and Rb4is CH3. In some variations of formula (12) described in the paragraphs above in which o2 is 4, each of RaJ, Rbi, Ra2, and j,2 is H and each of Ra3, ¾3, Ra- and Rb4is CH3. In some variations of formula (12) described in the paragraphs above in which o2 is 4, each of Rai, Rbi, Ra2, ¾2, Ras, and bsis CH3 and each of A4 and R¾4 is H. [357] In some variations of formula (12) described in the paragraphs above in which o2 is 4, each of Rai,RA2, and Ra3 is H and each of Rb!, Rb2, and Rb3 is CH3. In some variations of formula (12) described in the paragraphs above in which o2 is 4, ai is H, Rm is CH3, and each of Ra2, R 2, Ra3, and R is (Ί . In some variations of formula (12) described in the paragraphs above in which o2 is 4, aj is H, RM is CH3, and each of Ra2, ¾2, Ra3. a d ¾3 is H. In some variations of formula ( 12) described in the paragraphs above in which o2 is 4, each of Rai and Ra2 is H, each of Rw and Rb2 is CH3, and each of ^ and Rb3 is H. In some variations of formula (12) described in the paragraphs above in which o2 is 4, each of Ral and is H, each of Rbi and Rb2 is CH3, and each of A3 and Rb3 is CH3.
[358] In some variations of formula (12) described in the paragraphs above in which o2 is 4,
Rai and RM are H, Ra2 and Rb2 are H, and Rb3 are H, and Ra4 and Rb4 are '¾ ^ , In some variations of formula (12) described in the paragraphs above in which o2 is 4, Rai and Rj,i are H,
Ra2 and Rb2 are H, Ra3 and Rb3 are CH3, and A4 and R 4 are "¾ . In some variations of formula (12) described in the paragraphs above in which o2 is 4, Rai and bi are H, Ra2 and are CH3, as and R 3 are CH3, and Ra4 and R^ are " L . In some variations of formula (12) described in the paragraphs above in whic is 4, Raj and i are CH3, Ra2 and Rb2 are CH3, and Rb3 are CH3, and A4 and Rb4 are
Figure imgf000121_0001
[359] In some variations of formula (12) described in the paragraphs above in which o? is 4,
Figure imgf000121_0002
Raj and M are H, Ra2 and RB2 are H, ^ and R 3 are "*· and A4 and R 4 are . In some variations of formula (12) described in the paragraphs above in which o? is 4, Rai and Rbi are H, Ra2 and Rb2 are CH3, RA3 and Rb3 are '¾ and Ra4 and Rb are ^ . In some variations of formula ( 12) described in the paragraphs above in which o2 is 4, RAI and RM are
O . Ra2 and ¾2 are CH3, Ra3 and Rb3 are "^- and Ra4 and Rb4 are "^- . In some variations of formula (12) described in the paragraphs above in which o2 is 4, Ral is H, Rbi is CH3, Ra2 and are CH3, Ra3 and R 3 are ' *· , and Ra4 and Rb4 are " . In some variations of formula 12) described in the phs above in which is 4, Rai is H, ¾i is CH3, RA2 is H, R¾2 s
CH3, Ra3 and R,3 are
Figure imgf000122_0001
and Ra4 and M are
[360] In some variations of formula (12) described in the paragraphs above in which o2 is 4,
Rai and R¾i are H, Ra2 and R¾2 are VN£ RA3 and j,3 are " V¾N ^i", and Ra4 and R¾4 are ^ί . In some vari ations of formula (12) described in the paragraphs above in which o2 is 4, RaS and R¾i are CH3, ^ and Rb2 are "¾ , Ra3 and |,3 are "¾ , and Ra4 and ^ are "*· . In some variations of formula scribed in the paragraphs above in which o2 is 4, Rai is H, R|>i is
CH3, Ra2 and ¾2 are
Figure imgf000122_0002
Ra3 and R 3 are · and Ra4 and Rj, are . In some variations of formula (12) described in the paragraphs above in which <¾· is 4, RaJ and Rbj are
. _ w
"¾ Ra2 and Rb2 are '¾ Ra3 and R|,3 are "^- ^\ and Ra4 and Rj,4 are '¾ ^\
[361] In some variations of formula (12) described in the paragraphs above in which o2 is 4,
O
Rai and Rt>i are H, Ra2 and Rb2 are H, ^ and j,? are H, and R^ and ¾ are . In some variations of formula (12) described in the paragraphs above in which o? is 4, Ral and j,i are H,
O
Ra2 and Rj)2 are H, Ra3 and j,3 are CH3, and A and M are A '¾· ^c-* . In some variations of formula (12) described in the paragraphs above in which o2 is 4, aj and j,i are H, Ra2 and &2
O
are CH3, R.^ and R|>3 are CH3, and RA and R are s '¾A· e . In some variations of formula (12) described in the paragraphs above in which o2 is 4, ai and M are CH3, Ra2 and &2 are CH3,
A'
Ra3 and t,3 are CH3, and 34 and R¾4 are .
[362] In some variations of formula (12) described in the paragraphs above in which o2 is 4,
O
Ra3 and M are H, Ra2 and Rb2 are H, ^ and j,3 are "*· and Ra4 and M are v. In some variations of formula (12) described in the paragraphs above in which o2 is 4, Ral and Rj,i are H,
A A
Ra2 and ¾2 are CH3, Ra3 and i,3 are "¾· and Ra4 and RM are In some variations of formula (12) described in the paragraphs above in which o2 is 4, Rai and Rbi are CH3, a2 and
O O
Rb2 are CH3, RA3 and ¾ are "^- and A4 and ¾4 are ^\ In some variations of formula (12) described in the paragraphs above in which o2 is 4, RAS is H, RM is CH3, Ra2 and Rb2 are CH3, RA3 and R¾,3 are
Figure imgf000123_0001
In some variations of formula (12) described in the paragraphs above in which o2 is 4, RA3 is II, RB! is CH3, RA2 is H, 2 is CH3,
Figure imgf000123_0002
[363] In some variations of formula (12) described in the paragraphs above in which o2 is 4,
0 0 0
¾A <* ¾A / ¾A
Rai and bi are II, a2 and b2 are'¾- a3 and 3 are 'h- i , and RA4 and RB4 are'¾- . In some variations of formula (12) described in the paragraphs above in which o2 is 4, ai and Rbi are CH3, a2 and b2 are
Figure imgf000123_0003
In some variations of formula (12) described in the paragraphs above in which o2 is 4, Rai is H, i is
Figure imgf000123_0004
In some variations of formula (12) described in the paragraphs above in which o2 is 4, RAI and bi are
Figure imgf000123_0005
and Rb2 are
Figure imgf000123_0006
[364] In some variations of formula (12) described in the paragraphs above in which o? is 4,
Rai and R i are
Figure imgf000123_0007
. In some variations of formula (12) described in the paragraphs above in which o2 is 4, ai and bj are
Figure imgf000123_0008
In some variations of formula (12) described in the paragraphs above in which o2 is 4, ai and M are
r— 7 O
"¾ a2 and RB2 are H, a3 and 3 are CH3, and RA4 and RB4 are '¾· ? [365] In some variations of formula (12) described in the paragraphs above in which o? is 4,
Riii and M are Ra2 and n,? are "% ¾3 and Rb3 are H, and RA4 and Rj,4 are '^- <*\ In some variations of formula (12) described in the paragraphs above in which o2 is 4, RaS and R¾i
Figure imgf000124_0001
In some variations of formula (12) described in the paragraphs above in which o2 is 4, Rai and j,i are
Figure imgf000124_0002
'¾ a2 and j,2 are ' *· ^* . In some variations of formula (12) described in the paragraphs above in which o2 is 4, ai and M are
O
"¾ , a2 and R¾2 are , aj and ¾3 are H, and Ra4 and are '¾· .
[366] In some variations of formula (12) described in the paragraphs above in which o2 is 4, NC 2 and j,2 are N ^i %
Rai and RM are '^- Ra , Ra3 and Ι¾,3 are and Ra4 and Rb4 are
O
[367] In some variations of formula (12) described in the paragraphs above in which o? is 4,
O O
Rai and Rbi are "¾ Ra2 and are Ra3 and j>3 are H, and Ra4 and Rb4 are ^ . In some variations of formula ( 12) described in the paragraphs above in which o2 is 4, ai and j,i
O O
are " ^ , Ra2 and Rj,2 are '^- ^ and &3 are CH3, and Ra4 and ¾4 are ^\ In some variations of formula (12) described in the paragraphs above in which o is 4, Rai and M are
"¾ G , Ra2 and j)2 aie
Figure imgf000124_0003
In some variations of formula (12) described in the paragraphs above in which o2 is 4, as and RM are
O O
"¾ Ra2 and Rj>2 are % · Ra3 and are H, and Ra4 and R1( are % A· ^ , [368] In some variations of formula (12) described in the paragraphs above in which o? is 4,
Riii and R i are "¾ Ra2 and R 2 are
Figure imgf000125_0001
, and a4 and Rb4 are
O
[369] In some variations of formula (12) described in the paragraphs above in which o? is 4,
0 0 o
Rai and Rbi are A Ra2 and Rb2 are ' «a3 and b3 are H, and a4 and 4 are % '¾· . In some variations of formula (12) described in the paragraphs above in which o2 is 4, Rai and R i are
Figure imgf000125_0002
In some variations of formula (12) described in the paragraphs above in which o is 4, Rai and bi are
Figure imgf000125_0003
. In some variations of formula (12) described in the paragraphs above in which o2 is 4, Rai and bi are 0 0 o
¼· Ra2 and Rb2 are ½ Ra3 and Rb3 are H, and Ra4 and Rb4 are
[370] In some variations of formula (12) described in the paragraphs above in which o is 4,
Rai and bi are
Figure imgf000125_0004
[371] In some variations of formula (12) described in the paragraphs above in which o2 is 4,
Ra3 and Rb3 are H, Ra2 and Rb2 are H, and Ra3 and Rb3 and Ra4 and Rb4 together are . In some variations of formula (12) described in the paragraphs above in which o2 is 4, Rai and i are H, R^ and Rb2 are CH3, and Ra3 and Rj,3 and Ra4 and Rb4 together are ' L . In some variations of formula (12) described in the paragraphs above in which o? is 4, Ral and Ra2 are H,
Rbi and Rb2 are CH3, and and Rb3 and Ra4 and Rb4 together are [372] In some variati ons of formula (12) described in the paragraphs above in which o2 is 4,
Raj and j are H, Ra2 and R 2 are '¾ and a3 and 3 and Ra4 and R 4 together are . In some variations of formula (12) described in the paragraphs above in which o2 Rai and Rbj are " Ra2 and Rb2 are CH3, and Ra3 and Rb3 and Ra4 and Rb4 together are ' ¾ . In some variations of formula (12) described in the paragraphs above in which o2 is 4,
Ra3 is H, RbJ is CI¾, Ra2 and Rb2 are '¾ , and Ra3 and Rb3 and Ra4 and Rb together are
[373] In some variations of formula (12) described in the paragraphs above in which o? is 4,
O
Rai and R¾i are H, Ra2 and R 2 are and Ra3 and R 3 and Ra4 and Rb4 together are ^
In some variations of formula (12) described in the paragraphs above in which o2 is 4, Ra! and
9
j,i are "*· Ra2 and R 2 are CH3, and a3 and R 3 and Ra4 and R 4 together are ¾ V In some variations of formula (12) described in the paragraphs above in which o? is 4, Rai is H, R i is CH3, Ra2 and Rb2 are
Figure imgf000126_0001
and Ra3 and Rb3 and Ra4 and Rb4 together are ¾ V
[374] In some variations of formula (12) described in the paragraphs above in which o? is 4, and Rb3 and Ra4 and R 4 together
Figure imgf000126_0002
In some variations of formula (12) described in the paragraphs above in which o? is 4, and Ri,i are
Figure imgf000126_0003
Ra2 and Rb2 are and a3 and R 3 and Ra4 and Rb4 together are . In some variations of formula (12) described in the paragraphs above in which o2 is 4,
O O
% A/ A
Rai and Rb3 are '¾· Ra2 and Rb2 are - ^\ and ^ and Rb3 and Ra and Rb together are
[375] In some variations of formula (12) described in the paragraphs above in which o? is 4,
Rai and Rbj are "¾ Ra2 and Rb2 are "*~ and Ra3 and Rb3 and Ra4 and Rb4 together are [376] In some variations of formula (12) described in the paragraphs above in which <¾> is 4, Riii and ¾i and Ra2 and Rj>2 together are "¾ and R¾3 and b3 and Ra4 and R^ together are
[377] In some variations of formula (12) described in the paragraphs above, ring A is:
Figure imgf000127_0001
optionally substituted with halo or C1 -C6 linear or branched aikyl;
Figure imgf000127_0002
optionally substituted with halo or C1 -C6 linear or branched aikyl; or
Figure imgf000127_0003
Figure imgf000128_0001
optionally substituted with halo or C 1-C6 linear or branched aikyi.
[378] In some variations of formula (12) described in the paragraphs above, ring A is substituted with halo. In some variations, the halo is F, Br, I, or Ci.
[379] In some variations of formula (12) described in the paragraphs above, ring A is substituted with C1-C6 linear or branched alky! (e.g., C 1-C6, C1-C5, C1-C4, C1-C3, C 1-C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl).
[380] In some variations of formula (12) described in the paragraphs above, n is 1-4, 1 -3, 1-2, 2-4, 2-3, 3 4, 1, 2, 3, or 4.
[381] In some variations of formula (12) described in the paragraphs above, Dl is safranin-O. In some variations of formula (12) described in the paragraphs above, 1)2 is safranin-O. In some variations of formula (12) described in the paragraphs above, Dl and D2 are safranin-O.
[382] In some variations of formula (12) described in the paragraph above, the pendant phenyl ring of Dl is unsubstituted. In some variations of formula (12) described in the paragraph above, the pendant phenyl ring of 1)1 is substituted with 1-3 (e.g., 1-3, 1 -2, 1, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— NH2,— -NHR,— -NR2,— OH,— O",
— NHCOCH3,— HCOR, ΟΠ I : .— OR,— C2H5,— , and G.l k wherein R is C1-C6 linear or branched alkyl (e.g., C1 -C6, C 1 -C5, C1-C4, C 1 -C3, C1-C2, C I, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— N02,— NR3 +, halo (e.g., F, Br, CI, I), trihaiide (e.g., CF3, --CCI3, --CBr3, --CI3),— CN, - - SO3H, --COOH,—COOR,—CHO, and — COR, wherein R is C 1-C6 linear or branched alkyl (e.g., C 1-C6, C1-C5, C 1-C4, C 1-C3, CI- C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
[383] In some variations of formula (12) described in the paragraph above, the pendant phenyl ring of D2 is unsubstituted. In some variations of formula (12) described in the paragraph above, the pendant phenyl ring of D2 is substituted with 1-3 (e.g., 1-3, 1 -2, 1, 2, or 3) electron-donating or electro -with drawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— 'NH2,— -NHR,— NR2,— OH,— O",
— HCOCH3, -—NHCOR,— OCH3,— OR,— C2H5,— R, and— C6H5, wherein R is C 1-C6 linear or branched alkyl (e.g., C1 -C6, C 1 -C5, C1 -C4, C 1 -C3, C1 -C2, C I, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— 02,— ΝΙ^ , halo (e.g., F, Br, CI, I), trihaiide (e.g.,— CF3,— CCI3,— CBr3,— CI3),— CN, SO U,— COOH,— COOR,— CHO, and —COR, wherein R is C1-C6 linear or branched alkyl (e.g., C 1-C6, C1-C5, C 1-C4, C 1-C3, Cl - C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
[384] In some of the variations of formula (12) described above, Dl and D2 are safranin-0 moieties, as shown in formula (12a):
Figure imgf000130_0001
(12a) in which l l2, n, o , o2, ring A, Rai, ¾i, Ra2, ¾2, ¾ί, Rdi, ¾2, a d ]½ are as described in the paragraphs above, Ri, R?, R3, ¾, R5, and ¾ independently are absent or independently are selected from \i k— NHR,— NR2,—OH,— O",— NHCOCH3,— NHCOR,— OCH.
--C2H5, R, C,,! l NO ,— R3 +, halo (e.g., F, Br, CI, I), trihalide (e.g., --CF3, --CCI3, — CBr3, C I : },— CN,— SO3H,— COOH,— COOR,— CHO, and— COR), and R is C 1-C6 linear or branched alky! (e.g., C 1-C6, C 1-C5, C1-C4, C 1-C3, C1-C2, CI , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl).
[385] Some cationic dye dimers fall within formula (12b):
Figure imgf000130_0002
^b) _ which each of Dl and D2 is a cationic dye moiety; h, , n, independently are 1-4; o}, and o2 independently are 1-8; ring A is aryl, heteroaryl, cycloalkyl, or heterocyclyl; for each independent instance of Rai and s,i; ai
O
and Rj,i (1) independently are H or CH3, or (2) Rai and R¾i are ^ or L ^ , or (3) two of CRaiRbi are "^- **· ; for each independent instance of a2 and ^, a2 and Rj,2 (1) independently are H or CH3, or (2) ^ and R¾2 are 'x ** or "¾ , or (3) two of CRa2Rb2 are for each independent instance of Rci and R,u; Rci and ¾i (1 ) independently are or
CH3, or (2) ci and di are
Figure imgf000130_0003
or (j) two iRdi are for each independent instance of Rc2 and ϊ½; Re2 and ¾2 (1) independently are H or CH3, or (2) R^ and
R<!2 are
Figure imgf000131_0001
or (3) two of CRc2Rd2 are
[386] In some variations of formula (12b), each of Dl and D2 is a cationic dye moiety; ring . is aryf, heteroaryl, cycloalkyl, or heterocyclyl; n is 1 -4; // and L are each 1 ; o} and o2
O O
independently are 1-8; RaJ and Rj,j are 4 ; Ra2 and R¾2 are '¾ for each independent instance of Rci and Rfji, ci and Ι¾ι (1) independently are H or CH3, or (2) Rci and ^i are
O
≠ o orr ¾ '¾ * , o orr n (3U) twwoo n off f CRR.ci,Rdi a arree '¾ ¾ ; for each independent instance of c2 and
γ O (i2, c2 and (i2 (1) independently are H or CH3, or (2) R<;2 and R,¾2 are "¾ or ' *· , or (3) two of CRc2 d2 are "¾ V
O
[387] In some variations of formula (12b), n is 2; // and h are each 1 ; Ra! and Rj,i are '¾ ¾i ;
O
Ra2 and Rj>2 are ' L and each ring A independently is aryl, heteroaryl, cycloal kyl , or heterocyclyl, wherein the rings are joined together to form one of the regioisomeric moieties shown, where each ring A is exemplified as a phenyl ring:
Figure imgf000131_0002
In other similar variations of formula ( 12b), n is 3 or 4, each risig A independently is aryl, heteroaryl, cycloalkyl, or heterocyclyl and are linked together to form extended regioisomeric chains. In particular variations, ring A is aryl or heteroaryl.
[388] In some of the variations of formula (12b) described above, Dl and D2 are safranin-0 moieties, as shown in formula (12c):
Figure imgf000132_0001
(12c) in which //, l2, n, oh o2, ring A, RAJ, RM, Ra2, ¾2, ¾ι, ¾ι, ¾2 and Rd2 are as described for formula (12b), Ri, R?, R3, ¾, R5, an ¾ independently are absent or independently are selected from— H¾— NHR,— NR2,—OH,—0 — NHCOCH3,— NHCOR,— OCH3,— OR,— C2¾,
R, C\,i k— N02, \ R ; \ halo (e.g. , F, Br, CI, I), trihalide (e.g. , --CF3, --CO3, CBr3, — CI3),— CN,— SO3H,— COOH,— COOR,— CHO, and— COR), and R is C 1-C6 linear or branched alkyl (e.g. , C1 -C6, C1 -C5, C1 -C4, C 1 -C3, C 1 -C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl).
[389] In some of the variations of formula (12c), each oj and o2 is 1-8, each , Rai, Rc2 and <i2 is H, and Rj to ¾ are as described above for formula (12b). In some of these variations, o} and o2 are 6 or 8, each Ra and Rh is H, and each of Ri to Re independently is absent or is a halo. In particular variations, o2 and o2 are 6 or 8, each Ra and Rif is H, and i to ¾ are ail absent.
[390] In some of the variations of formula (12c), each oj and o? is 1-8, each Rd, di, c2 and (i2 are either H or and R{ to e are as described above for formula (12b). In some of these variations, o}
Figure imgf000132_0002
and o2 are 6 or 8, Ra and Rb are either H or each of Rj to Re independently is absent or is a halo. In particular variations, o} and o2 are 6 or 8, Ra and j> are either H or
Figure imgf000132_0003
i to Re are all absent.
[391] In some of the variations of formula (12c), each o} and o2 is 1-8, each Rc!, Rdj. Rci and
Rij2 are either H or
Figure imgf000132_0004
, and j to R6 are as described above for formula (12b). In some of these variations, o} and o2 are 6 or 8, Ra and Rb are either H or
Figure imgf000132_0005
and each of ¾ to R6 independently is absent or is a halo. In particular variations, o} and o2 are 6 or 8, Ra and R¾ are O
either H or '¾ , and Ri to Re are all absent.
In some of the variations of formula (12c), each oj and o2 is 1-8, each , Rdi, c2 and
Ro2 are either H or two of CRciRai and C ^ cu are and i to ¾ are as described above for formula (12b). In some of these variations, 01 and o2 are 6 or 8, each Rd, iii, c2 and ,S2 are either II or two of CRdRdi and CRc2 <i2 are \ and each of Ri to R45
independently is absent or is a halo. In particular variations, o} and o2 are 6 or8, each Rd, ^i, s;2 and d2 are either H or two of CRdRdi and C ^ eu are ' <■ ¾ , and R{ to « are all absent.
[393] One of ski ll in the art can readily visualize and prepare other cationic multimers falling within formulae (12) or (12b) in which other cationic dye moieties are used in place of one or both of the safranin-0 moieties,
[394] Some cationic dye dimers fall within formula (13):
Figure imgf000133_0001
wherein each of Dl and D2 is a cationic dye moiety is 0-6, and rij
[395] In some variations of formula (13), Dl and 1)2 are different cationic dye moieties. In other variations of formula (13), Dl and D2 are the same cationic dye moiety. In some variations of formula (13), Dl and 1)2 are independently selected from the group consisting of safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue.
)6] In some variations of formula (13) described in the paragraphs above, n is 0-6, 0-5, 0-4, 0-3, 0-2, 0-1, 1-6, 1-5, 1-4, 1-3, 1-2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, 5-6, 0, I, 2, 3, 4, 5, or 6.
[397] In some variations of formula (13) described in the paragraphs above, n} is 1-4, 1-3, 2-4, 2-3, 3-4, I, 2, 3, or 4. [398] In some variations of formula (13) described in the paragraphs above, 1)1 is safranin-O. In some variations of formula (13) described in the paragraphs above, D2 is safranin-O. In some variations of formula (13) described in the paragraphs above, Dl and D2 are safranin-O.
[399] In some variations of formula (13) described in the paragraph above, the pendant phenyl ring of Dl is unsubstituted. In some variations of formula (13) described in the paragraph above, the pendant phenyl ring of Dl is substituted with 1-3 (e.g., 1 -3, 1-2, 1 , 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— NH?,— NHR,— 2,— OH,— O",
--NHCOCH3, N I K OR --OCH3, -----OR, --C2H5, --R, and O.S k wherein R is C1 -C6 linear or branched aikyi (e.g., C 1-C6, C 1-C5, C 1-C4, C 1-C3, C 1-C2, CI, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched aikyi ). In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— NO2,— R3 1, halo (e.g., F, Br, CI, I), trihalide (e.g., --CF3, --CCI3, ---CBr3, --CI3), --CN, --SO3H, --COOH, --COOR, --CHO, and — COR, wherein R is C 1-C6 linear or branched alkyl (e.g., C 1-C6, C 1-C5, C1-C4, C 1-C3, C l - C2, CI , C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched aikyi).
[400] In some variations of formula (13) described in the paragraph above, the pendant phenyl ring of D2 is unsubstituted. In some variations of formula (13) described in the paragraph above, the pendant phenyl ring of D2 is substituted with 1 -3 (e.g., 1 -3, 1-2, 1 , 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— -NH2,— HR,— R2,— OH,— O",
— NHCOCH3, X I li OR (X I k—OR,— C2H5,— R, and G,i k wherein R is C 1-C6 linear or branched aikyi (e.g., C 1-C6, C 1-C5, C 1-C4, C 1-C3, C1-C2, CI , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched aikyi ). In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— O?,— R3 , halo (e.g., F, Br, CI, I), trihalide (e.g., --CF3, --CCI3, ---CBr3, --CI3), --CN, --SO3H, --COOH, --COOR, --CHO, and — COR, wherein R is C 1-C6 linear or branched alkyl (e.g., C 1-C6, C 1-C5, C1-C4, C 1-C3, C l- C2, CI , C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched aikyi ).
1 j j Examples of Cationic Dye Trimers and Other Multimers
Some cationic dye trimers fall within formula (14):
Figure imgf000135_0001
, in which each of Dl, D2, and D3 is a cationic dye moiety, n is 0-6, m is 1-4, is 0-6, and mi is 0-6. f 402] In some variations of formula (14), Dl, D2, and D3 are different cationic dye moieties. In some variations of formula (14), Dl, D2, and D3 are the same cationic dye moiety. In other variations of formula (14), Dl and D2 are the same cationic dye moiety and D3 is a different cationic dye moiety. In other variations of formula (14), Dl and D3 are the same cationic dye moiety and D2 is a different catiomc dye moiety. In other variations of formula (14), D2 and D3 are the same cationic dye moiety and Dl is a different cationic dye moiety. In some variations of formula (14), each of Dl, D2, and D3 independently is selected from the group consisting of safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue.
[403] In some variations of formula (14) described in the paragraphs above, n is 0-6, 0-5, 0-4, 0-3, 0-2, 0-1, 1 -6, 1-5, 1-4, 1-3, 1-2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, 5-6, 0, 1 , 2, 3, 4, 5, or 6.
[404] In some variations of formula (14) described in the paragraphs above, W/ is 1-4, 1-3, 1 -2, 2-4, 2-3, 3-4, 1 , 2, 3, or 4,
[405] In some variations of formula (14) described in the paragraphs above, nh is 0-6, 0-5, 0-4, 0-3, 0-2, 0-1 , 1 -6, 1-5, 1 -4, 1-3, 1-2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, 5-6, 0, 1 , 2, 3, 4, 5, or 6.
[406] In some variations of formula (14) described in the paragraphs above, nhi is 1-4, 1-3, 1 -2, 2-4, 2-3, 3-4, 1 , 2, 3, or 4.
[407] In some variations of formula (14) described in the paragraphs above, Dl is safranin-O. In some variations of formula (14) described in the paragraphs above, D2 is safranin-O. In some vari ations of formula (14) described in the paragraphs above, D3 is safranin-O. In some variations of formula (14) described in the paragraphs above, Dl and D2 are safranin-O. In some variations of formula (14) described in the paragraphs above, 1)1 and D3 are safranin-O. In some variations of formula (14) described in the paragraphs above, D2 and D3 are safranin-O.
[408] In some variations of formula (14) described in the paragraph above, the pendant phenyl ring of Dl is unsubstituted. In some variations of formula (14) described in the paragraph above, the pendant phenyl ring of Dl is substituted with 1-3 (e.g., 1 -3, 1-2, 1 , 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— -NH2,— NHR,— NR2,— OH,— O",
— NHCOCH3,— NHCOR,— OCH3,—OR,— C2H5,— R, and— C6¾, wherein R is C 1-C6 linear or branched alky! (e.g., C 1-C6, C 1-C5, C1-C4, C 1-C3, C1-C2, CI , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— -NO2,— - R3 +, halo (e.g., F, Br, CI, I), trihalide (e.g.,— CF3,— CCI3,— CBr3, (' ! : )..— CN,— SO3H,— COOH,— COOR,— CHO, and — COR, wherein R is C1-C6 linear or branched alkyl (e.g., C 1 -C6, C 1-C5, C1 -C4, C 1-C3, C l- C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
[409] In some variations of formula (14) described in the two paragraphs above, the pendant phenyl ring of D2 is unsubstituted. In some variations of formula (14) described in the paragraph above, the pendant phenyl ring of D2 is substituted with 1-3 (e.g., 1-3, 1-2, I, 2, or 3) electron- donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— NH2,— NHR,— NR2,— OH,— O",
— NHCOCH3,— -NHCOR, --OCH3,—OR, --C2H5, --R, and C,,l k wherein R is C1-C6 linear or branched alkyl (e.g., C I-C6, C 1-C5, C1-C4, C I-C3, C1-C2, C I , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— -N02,— -NR3 +, halo (e.g., F, Br, CI, I), trihalide (e.g.,— CF3,— CCI3,— CBr3,— CI3),— CN,— SO3H, -—COOH,— COOR,—CHO, and — COR, wherein R is C1.-C6 linear or branched al kyl (e.g., C 1 -C6, C1-C5, C 1 -C4, C 1 -C3, C l- C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl). [410] In some variations of formula (14) described in the three paragraphs above, the pendant phenyl ring of D3 is unsubstituted. In some variations of formula (14) described in the paragraph above, the pendant phenyl ring of D3 is substituted with 1-3 (e.g., 1 -3, 1-2, 1, 2, or 3) electron- donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of D3 is substituted, the substituents are selected independently from— -NH2,— HR,—NR2,— OH,— O",
— ICOCH3,— NHCOR,— OCH3,—OR,— C2H5,— R, and C-j k wherein R is C1-C6 linear or branched alky! (e.g., C1-C6, C1-C5, C1-C4, C1-C3, C1-C2, CI , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of 1)3 is substituted, the substituents are selected independently from— 02,— R3 , halo (e.g., F, Br, CI, I), trihaiide (e.g., --CF3, CCU ---CBr3,— CI3),— CN, --SO3H, --COOH, --COOR, --CHO, and — COR, wherein R is C1-C6 linear or branched alkyl (e.g., C1-C6, C1-C5, C1-C4, C 1-C3, Cl- C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
Some cationic dye trimers fall within formula (15):
Figure imgf000137_0001
> , i n w hi ch each of I) 1 ,
D2, and D3 is a cationic dye moiety, n and nb independently are 0-6, and n} and nh}
independently are 1-4.
[412] In some variations of formula (15), Dl, D2, and D3 are different cationic dye moieties. In some variations of formula (15), Dl, D2, and D3 are the same cationic dye moiety. In other variations of formula (15), Dl and D2 are the same cationic dye moiety and D3 is a different cationic dye moiety. In other variations of formula (15), Dl and D3 are the same cationic dye moiety and D2 is a different catiomc dye moiety. In other variations of formula (15), D2 and D3 are the same cationic dye moiety and Dl is a different cationic dye moiety. In some variations of formula (15), each of Dl, D2, and D3 independently is selected from the group consisting of safranin-O, toiuidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue. [413] In some variations of formula (15) described in the paragraphs above, n is « is 0-6, 0-5, 0-4, 0-3, 0-2, 0-1, 1-6, 1-5, 1-4, 1-3, 1-2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, 5-6, 0, 1, 2, 3, 4, 5, or 6,
[414] In some variations of formula (15) described in the paragraphs above, «/ is 1-4, 1-3, 1-2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[415] In some variations of formula (15) described in the paragraphs above, nb is 0-6, 0-5, 0-4, 0-3, 0-2, 0-1, 1 -6, 1-5, 1-4, 1-3, 1-2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, 5-6, 0, 1 , 2, 3, 4, 5, or 6,
[416] In some variations of formula (15) described in the paragraphs above, % is 1-4, 1-3, 1 -2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[417] In some variations of formula (15) described in the paragraphs above, 1)1 is safranin-O. In some variations of formula (15) described in the paragraphs above, D2 is safranin-O. In some variations of formula (15) described in the paragraphs above, D3 is safranin-O. In some variations of formula (15) described in the paragraphs above, Dl and D2 are safranin-O. In some variations of formula (15) described in the paragraphs above, Dl and D3 are safranin-O. In some variations of formula ( 15) described in the paragraphs above, D2 and D3 are safranin-O.
[418] In some variations of formula (15) described in the paragraph above, the pendant phenyl ring of Dl is unsubstituted. In some variations of formula (15) described in the paragraph above, the pendant phenyl ring of Dl is substituted with 1-3 {e.g., 1-3, 1-2, 1, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of Dl is substituted, the
substituents are selected independently from— -NH2,— NHR,— NR2,— OH,— O",
— NHCOCH3, --NHCOR, --OCH3,—OR, --C2H5,—R, and C,,l k wherein R is C1-C6 linear or branched alkyl (e.g., C1-C6, C1-C5, C1-C4, C1-C3, C1-C2, CI , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— -N02,— -N 3 +, halo (e.g., F, Br, CI, I), trihalide (e.g.,— CF3,— CCI3,— CBr3,— CI3),— CN,— SO3H,— COOH,— COOR,— CHO, and — COR, wherein R is C1-C6 linear or branched alkyl (e.g., C 1 -C6, C1-C5, C1 -C4, C1-C3, Cl- C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl). [419] In some variations of formula (15) described in the two paragraphs above, the pendant phenyl ring of D2 is unsubstituted. In some variations of formula (15) described in the paragraph above, the pendant phenyl ring of D2 is substituted with 1 -3 (e.g., 1 -3, 1-2, 1 , 2, or 3) electron- donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— ·ΝΗ2,— NHR,— NR2,— OH,— O",
— ICOCH3,—NHCOR,— OCH3,—OR,— C2H5,— R, and C-j k wherein R is C 1-C6 linear or branched alky! (e.g., C 1-C6, C 1-C5, C1-C4, C 1-C3, C1-C2, CI , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of 1)2 is substituted, the substituents are selected independently from— N02,— NR3 , halo (e.g., F, Br, CI, I), trihaiide (e.g., --CF3, --CCI3, ---CBr3, --CI3), --CN, --SO3H, --COOH, --COOR,— CHO, and — COR, wherein R is C1-C6 linear or branched alkyl (e.g., C 1 -C6, C 1-C5, C1 -C4, C 1-C3, C l- C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched aikyi ).
[420] In some variati ons of formula (15) described in the three paragraphs above, the pendant phenyl ring of D3 is unsubstituted. In some variations of formula (15) described in the paragraph above, the pendant phenyl ring of D3 is substituted with 1-3 (e.g., 1-3, 1-2, 1, 2, or 3) electron- donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of D3 is substituted, the substituents are selected independently from— -NH2,— 'NHR,— NR2,— OH,— O",
--NHCOCH3,— -NHCOR, --OCH3,—OR,— C2H5,— R, and C,,l k wherein R is C1-C6 linear or branched alkyl (e.g., C1-C6, C 1-C5, C1-C4, C 1-C3, C1-C2, C I , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of D3 is substituted, the substituents are selected independently from— -N02,— -NR3 +, halo (e.g., F, Br, CI, I), trihaiide (e.g.,— CF3,— CCI3,— CBr3,— CI3),— CN,— SO3H,— COOH,— COOR,— CHO, and — COR, wherein R is C1.-C6 linear or branched al kyl (e.g., C I -C6, C1-C5, C I -C4, C 1 -C3, C l- C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
Some cationic dye trimers fall within formula (16):
Figure imgf000140_0001
^ , in which each of Dl, D2, and D3 is a cationic dye moiety, n and nb independently are 0-6; tti and w/ independently are 1-4; for each independent instance of Raj and I½ Rai and I¾i (1) independently are H or CH3, or (2) ai and
O
ibi are or ¾ or (3) two of CRaiRbi are ; and, for each i ce of Ra2 and j,2, ¾2 and Rb2 (1) independently are H or CH3, or (2) Ra2 and
Figure imgf000140_0002
O
\ or (3) two of CRaiRbi are ,
[422] In some variations of formula (16), Dl, D2, and D3 are different cationic dye moieties. In some variations of formula ( 16), Dl , D2, and D3 are the same catiomc dye moiety. In other variations of formula ( 16), Dl and D2 are the same cationic dye moiety and D3 is a different cationic dye moiety. In other variations of formula (16), Dl and D3 are the same cationic dye moiety and D2 is a different cationic dye moiety. In other variations of formula (16), D2 and D3 are the same cationic dye moiety and Dl is a different cationic dye moiety. In some variations of formula ( 16), each of Dl, D2, and D3 independently is selected from the group consisting of safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue.
[423] In some variations of formula (16) described in the paragraphs above, n is 0-6, 0-5, 0-4, 0-3, 0-2, 0-1, 1-6, 1 -5, 1-4, 1 -3, 1-2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, 5-6, 0, 1, 2, 3, 4, 5, or 6.
In some variations of formula (16) described in the paragraphs above, «/ is 1-4, 1-3, 1-2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[425] In some variations of formula (16) described in the paragraphs above, nb is 0-6, 0-5, 0-4, 0-3, 0-2, 0-1, 1-6, 1-5, 1-4, 1-3, 1-2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, 5-6, 0, 1, 2, 3, 4, 5, or 6.
[426] In some variations of formula (16) described in the paragraphs above, n^i is 1-4, 1-3, 1-2, 2-4, 2-3, 3-4, 1, 2, 3, or 4. [427] In some variations of formula (16) described in the paragraphs above, Rai is H and ¾ι is H. In some variations of formula (16) described in the paragraphs above, Rai is H and RM is CH3. In some variations of formula (16) described in the paragraphs above, Rai and RM are both some variations of formula (16) described in the paragraphs above, Rai and RM are In some variations of formula (16) described in the paragraphs above, Rai and Rbi are n some variations of formula (16) described in the paragraphs above, two of C ai j,i are
Figure imgf000141_0001
[428] In some variations of formula (16) described in the paragraphs above, Ra2 is H and ¾2 is H, In some variations of formula (16) described in the paragraphs above, Ra2 is H and R^ is O . In some variations of formula (16) described in the paragraphs above, Ra2 and j>2 are both n some variations of formula (16) described in the paragraphs above, Ra2 and i»2 are n some variations of formula (16) described in the paragraphs above, Ra2 and ¾2 are n some variations of formula (16) described in the paragraphs above, two of CRa2I¾,2 are
Figure imgf000141_0002
[429] In some variations of formula (16) described in the paragraphs above, Dl is safranin-O. In some variations of formula (16) described in the paragraphs above, D2 is safranin-O. In some variations of formula (16) described in the paragraphs above, D3 is safranin-O. In some variations of formula (16) described in the paragraphs above, Dl and D2 are safranin-O. In some variations of formula (16) described in the paragraphs above, Dl and D3 are safranin-O. In some variations of formula (16) described in the paragraphs above, D2 and D3 are safranin-O.
[430] In some variations of formula (16) described in the paragraph above, the pendant phenyl ring of Dl is un substituted. In some variations of formula ( 16) described in the paragraph above, the pendant phenyl ring of Dl is substituted with 1-3 (e.g., 1-3, 1-2, 1, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of Dl is substituted, the
substituents are selected independently from— NH2,— NHR,— NR2,— OH,— O",
M lCOC ! h.— NHCOR, O . -----OR, ---C2H5, --R, and C„i k wherein R is C1-C6 linear or branched alkyl (e.g., C 1 -C6, C 1 -C5, C 1-C4, C 1 -C3, C 1-C2, CI, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched aikyi). In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— N02,— NR , halo (e.g., F, Br, CI, I), trihalide (e.g.,— CF3, C U. ---CBr3, --CI3),— CN, --SO3H, --COOH, --COOR, --CHO, and — COR, wherein R is C 1-C6 linear or branched alkyl (e.g., C 1-C6, C 1-C5, C1-C4, C 1-C3, C l - C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
[431] In some variations of formula (16) described in the two paragraphs above, the pendant phenyl ring of D2 is unsubstituted. In some variations of formula (16) described in the paragraph above, the pendant phenyl ring of D2 is substituted with 1 -3 (e.g. , 1 -3, 1-2, 1 , 2, or 3) electron- donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— -NH2,— NHR,— R2,— OH,— O",
— NHCOCH3,— NHCOR, (X I k— OR,— C2H5,— R, and G,! k wherein R is C 1-C6 linear or branched alkyl (e.g., C 1-C6, C 1-C5, C 1-C4, C 1-C3, C1-C2, C I , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl ). In some embodiments in which the pendant phenyl ring of 1)2 is substituted, the substituents are selected independently from— O?,— NR3 , halo (e.g., F, Br, CI, I), trihalide (e.g., --CF3, --CCI3, ---CBr3, --CI3),— CN, SO ;! !, --COOH, --COOR, --CHO, and — COR, wherein R is C 1-C6 linear or branched alkyl (e.g. , C 1-C6, C 1-C5, C1-C4, C 1-C3, C l- C2, CI , C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
[432] In some variations of formula (16) described in the three paragraphs above, the pendant phenyl ring of D3 is unsubstituted. In some variations of formula (16) described in the paragraph above, the pendant phenyl ring of D3 is substituted with 1 -3 (e.g., 1 -3, 1-2, 1 , 2, or 3) electron- donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of D3 is substituted, the substituents are selected independently from— -NH2,— NHR,— NR2,— OH,— O",
— NHCOCH3,— HCOR,— OCH3,—OR,— C2H5,— , and— C6¾, wherein R is C 1-C6 linear or branched alkyl (e.g., C 1-C6, C 1-C5, C1-C4, C 1-C3, C1-C2, CI , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl ). In some embodiments in which the pendant phenyl ring of 1)3 is substituted, the substituents are selected independently from— -N02,— -NR3 +, halo (e.g., F, Br, CI, I), trihalide (e.g. ,— CF3,— CCI3,— CBr3, (' ! : )..— CN,— SO3H,— COOH,— COOR,— CIIO, and —COR, wherein R is C1-C6 linear or branched alkyl (e.g., C1-C6, C1 -C5, C1-C4, C1-C3, Cl - C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
[433] Some cationic dye trimers fall within formula (1 7):
Figure imgf000143_0001
^ ^ , in which each of Dl, D2, and
D3 is a cationic dye moiety; kj is 2-10; k2 is 2-10; for each independent instance of Rai and Rbi,
O
Rai and M (1) independently are H or CH3, or (2) Rai and R|>i are ^ or "¾ * or (3) two of CRaiRbi are "¾ ¾ ; and, for each independent instance of Ra? and j,?, a2 and ¾2 (1)
— O
independently are H or CH3, or (2) ^ and ¾2 are ' O¾Q or " 0¾-0 # or (3) two of CRa2Rb2 are
[434] In some variations of formula (17), Dl, D2, and D3 are different cationic dye moieties. In some variations of formula (17), Dl, D2, and D3 are the same cationic dye moiety. In other variations of formula (17), Dl and D2 are the same cationic dye moiety and D3 is a different cationic dye moiety. In other variations of formula (17), Dl and D3 are the same cationic dye moiety and D2 is a different catiomc dye moiety. In other variations of formula (17), D2 and D3 are the same cationic dye moiety and Dl is a different cationic dye moiety. In some variations of formula (17), each of Dl, D2, and D3 independently is selected from the group consisting of safranin-O, toiuidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue.
[435] In some variations of formula (17) described in the paragraphs above, ki is 2-10, 2-9, 2-8, 2-7, 2-6, 2-5, 2-4, 2-3, 3-10, 3-9, 3-8, 3-7, 3-6, 3-5, 3-4, 4-10, 4-9, 4-8, 4-7, 4-6, 4-5, 5-10, 5-9, 5- 8, 5-7, 5-6, 6-10, 6-9, 6-8, 6-7, 7-10, 7-9, 7-8, 8-10, 8-9, 9-10, 2, 3, 4, 5, 6, 7, 8, 9, or 10.
[436] In some variations of formula (17) described in the paragraphs above, k2 is 2-10, 2-9, 2-8, 2-7, 2-6, 2-5, 2-4, 2-3, 3-10, 3-9, 3-8, 3-7, 3-6, 3-5, 3-4, 4-10, 4-9, 4-8, 4-7, 4-6, 4-5, 5-10, 5-9, 5- 8, 5-7, 5-6, 6-10, 6-9, 6-8, 6-7, 7-10, 7-9, 7-8, 8-10, 8-9, 9-10, 2, 3, 4, 5, 6, 7, 8, 9, or 10. [437] In some variations of formula (17) described in the paragraphs above, each Rai is H and each Rj,i is H. In some variations of formula (17) described in the paragraphs above, each Rai is H and each RM is CH3. In some variations of formula (17) described in the paragraphs above, each Rai and ¾i is
Figure imgf000144_0001
, In some variations of formula (17) described in the paragraphs above,
O
each Ral and ¾i is . In some variations of formula ( 17) described in the paragraphs above, each two of CRaiRbi are
[438] In some variations of formula (17) described in the paragraphs above, in a first occurrence of Rai and Rbi, each of Rai and Rbi is H, and the remaining occurrences of RAI and ex are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in a first occurrence of Rai and Rbi, each of ai and i is ( I f and the remaining occurrences of Rai and Rbi are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in a first occurrence of ai and RW, a first Raj is H, a first M is CH3, and the remaining occurrences of Rai and M are as defined above for formula (17). In some variations of ) described in the paragraphs above, in a first occurrence of Rai and Rbi, Rai and i
Figure imgf000144_0002
and the remaining occurrences of Rai and Rbi are as defined above for formula (17). In some variations of formula (17) described in the paragraph s above, in a first occurrence of Rai and Rbi, aj and R1(i are
Figure imgf000144_0003
, and the remaining occurrences of Rai and Rbi are as defined above for formula (17).
[439] In some variations of formula (17) described in the paragraphs above, in two occurrences of Rai and Rbi, each of Rai and ¾i is H, and the remaining occurrences of Rai and Rbi are as defined above for formula (17), In some variations of formula (17) described in the paragraphs above, in two occurrences of Rai and Rbi, each of Rai and I¾>i is CH3, and the remaining occurrences of Rai and bi are as defined above for forniuia (17). In some variations of formula (17) described in the paragraphs above, in two occurrences of Rai and i, two of Rai are H, two of bj are CH3, and the remaining occurrences of Rai and Rbi are as defined above for formula (17), In some variations of formula (17) described in the paragraphs above, in two occurrences of
Rai and Rbi, Rai and bi are
Figure imgf000144_0004
and the remaining occurrences of Rai and Rbi are as defined above for formula (17). In some variations of formula ( 17) described in the paragraphs above, in two occurrences of Rai and R , Rai and R¾i are
Figure imgf000145_0001
and the remaining occurrences of Rai and ¾i are as defined above for formula (17).
[440] In some variations of formula (17) described in the paragraphs above, in three occurrences of Rai and , each of Rai and RM is H, and the remaining occurrences of RAI and RM are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in three occurrences of Rai and Rm, each of Rai and M is CH3, and the remaining occurrences of Raj and are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in three occurrences of Rai and RM, three of Rai are H, three of are CH3, and the remaining occurrences of RA{ and M are as defined above for formula (17). In some variations of formula 17) described in the paragraphs above, in three occurrences of ai and RM, ai and R¾i
Figure imgf000145_0002
and the remaining occurrences of ai and j>i are as defined above for formula (17). In some variations of formula ( 17) described in the paragraphs above, in three occurrences of RA{ and RM, RaJ and RM are
Figure imgf000145_0003
, and the remaining occurrences of RAI and M are as defined above for formula ( 17).
[441] In some variations of formula (17) described in the paragraphs above, in four occurrences of Rai and RM, each of Rai and R¾i is H, and the remaining occurrences of Rai and RM are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in four occurrences of Rai and , each of Rai and is CH3, and the remaining occurrences of RAI and M are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in four occurrences of Rai and , four of Rai are H, four of are CH3, and the remaining occurrences of Rai and are as defined above for formula (17). In some variations of formula described in the paragraphs above, in four occurrences of RA} and M, Rai and RM are
Figure imgf000145_0004
and the remaining occurrences of ai and M are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in four occurrences of R¾i and , ai and are
Figure imgf000145_0005
and the remaining occurrences of Rai and M are as defined above for formula (1 7).
[442] In some variations of formula (17) described in the paragraphs above, in five occurrences of Rai and Rw, each of Rai and R1(i is H, and the remaining occurrences of Rai and RM are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in five occurrences of Ra! and w, each of Rai and M is CH3, and the remaining occurrences of Rai and ¾ι are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in five occurrences of ai and Rbi, five of ai are H, five of Rbi are CH3, and the remaining occurrences of Rai and Rbi are as defined above for formula (17). In some variations of form 17) described in the paragraphs above, in five occurrences of Rai and Rbi, Rai and Rbi are
Figure imgf000146_0001
and the remaining occurrences of Rai and Rt>i are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in five occurrences of Rai and RM, Rai and RM are
Figure imgf000146_0002
and the remaining occurrences of ai and ^ are as defined above for formula (17).
[443] In some variations of formula (17) described in the paragraphs above, in six occurrences of Rai and Rbi, each of Rai and Rbi is H, and the remaining occurrences of Rai and i are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in six occurrences of Rai and Rbi, each of Rai and Rbi is CH3, and the remaining occurrences of Rai and bi are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in six occurrences of Rai and Rbi, six of Rai are H, six of bi are CH3, and the remaining occurrences of Ra{ and i are as defined above for formula ( 17). In some variations of formula (17) described in the paragraphs above, in six occurrences of
Rai and RM, Rat and R i are
Figure imgf000146_0003
and the remaining occurrences of Rai and M are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in
O
six occurrences of ai and Rbi, Rai and bi are " A¾ t, and the remaining occurrences of Rai and Rbi are as defined above for formula ( 17).
[444] In some variations of formula (17) described in the paragraphs above, in seven occurrences of ai and Rbi, each of Rai and bi is H, and the remaining occurrences of Rai and bi are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in seven occurrences of Rai and R i, each of Rai and Rbi is CH3, and the remaining occurrences of Raj and bj are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in seven occurrences of Rai and Rbi, seven of Rai are H, seven of RM are CH3, and the remaining occurrences of Rai and RM are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in seven occurrences of Ra! and Rw, Rai and are , and the remaining occurrences of Rai and RM are as defined above for formula (17). In some variations of formula (17) described in
O
the paragraphs above, in seven occurrences of Rai and RM, ai and ¾i are "¾ and the remaining occurrences of ai and R¾i are as defined above for formula (17).
[445] In some variations of formula (17) described in the paragraphs above, in eight occurrences of aj and Rt>i, each of Ra{ and RM is H, and the remaining occurrences of Rai and Rbi are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in eight occurrences of aj and j,j, each of Ra{ and j,t is CH3, and the remaining occurrences of Rai and R|>i are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in eight occurrences of Ra{ and Rj,i, eight of Rai are H, eight of M are CH3, and the remaining occurrences of Rai and RM are as defined above for formula ( 7). In some variations of 7) described in the paragraphs above, in eight occurrences of ai and M, Rai and Rt>i
Figure imgf000147_0001
, and the remaining occurrences of ai and RM are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in eight occurrences of Rai and ϊ¾ι, Rai and Rbi are
Figure imgf000147_0002
and the remaining occurrences of Raj and ¾i are as defined above for formula (17).
[446] In some variations of formula (17) described in the paragraphs above, in nine occurrences of Ra{ and Rj,t, each of Rai and M is H, and the remaining occurrences of Ra{ and j,i are as defined above for formula (17), In some variations of formula (17) described in the paragraphs above, in nine occurrences of Rai and RM, each of Raj and ^i is CH3, and the remaining occurrences of Rai and RM are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in nine occurrences of Rai and ¾j , nine of Rai are H, nine of w are C¾, and the remaining occurrences of Rai and 1(i are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in nine occurrences of Rai and RM, Rai and j,i are " w¾ and the remaining occurrences of Rai and j,i are as defined above for formula (17), In some variations of formula (17) described in the
0
paragraphs above, in nine occurrences of Rai and R1(i, Rai and RM are '¾ and the remaining occurrences of Rai and Rbi are as defined above for formula (17), [447] In some variations of formula (17) described in the paragraphs above, in ten occurrences of Rai and Rw, each of Rai and RM is H, and the remaining occurrences of Rai and j,j are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in ten occurrences of Rai and Rbi, each of Rai and ¾i is CH3, and the remaining occurrences of Rai and Rbi are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in ten occurrences of Raj and ¾i , ten of Rai are H, ten of Rbi are CH , and the remaining occurrences of Raj and bi are as defined above for formula
(17), In some variations of formula (17) described in the paragraphs above, in ten occurrences of
Rai and Rbi, Rai and ϊ¾ι are
Figure imgf000148_0001
and the remaining occurrences of Rai and Rbi are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in
O
ten occurrences of Rai and Rbi, Rai and ¾ι are ' , and the remaining occurrences of Rai and Rbi are as defined above for formula (17).
[448] In some variati ons of formul a (17) described in the paragraphs above, two occurrences of
Rai and ¾i are "'ζ and the remaining occurrences of Rai and Rbi are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, four occurrences of Rai and i are - and the remaining occurrences of Rai and ¾i are as defined above for formula (1 7), In some variations of formula (17) described in the paragraphs above, six occurrences of Raj and bi are ^ ^^i^ and the remaining occurrences of Rai and Rbi are as defined above for formula (17), In some variations of formula (17) described in the paragraphs above, eight occurrences of Rai and bi are ^ and the remaining occurrences of Rai and Rbi are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, five occurrences of Rai and i are t- V
In some variations of formula (17) described in the paragraphs above, each Ra2 is H and each Rb2 is H. In some variations of formula (17) described in the paragraphs above, each Ra2 is H and each Rb2 is CH3. In some variations of formula (17) described in the paragraphs above, each Ra2 and I¾2 is . In some variations of formula ( 1 7) described in the paragraphs above, O
each Ra2 and R¾2 is "x ^\ In some variations ot formula (17) described in the paragraphs above, each two of CR^R^ are y ""*·
In some variations of formula (17) described in the paragraphs above, in a first occurrence of Ra2 and Ι½, each of and Rj,2 is H, and the remaining occurrences of Ra2 and Rj,2 are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in a first occurrence of Ra2 and Rj,2, each of Ra2 and j)2 is CH3, and the remaining occurrences of Ra2 and Rj,2 are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in a first occurrence of Ra2 and Rj,2, a first a2 is H, a first Rt>2 is CH3, and the remaining occurrences of Ra2 and ¾2 are as defined above for formula (17). In some vari ations of formula (17) described in the paragraphs above, in a first occurrence of Ra2 and Rj,2, Ra2 and Rb2 are '¾ , and the remaining occurrences of Ra2 and ¾2 are as defined above for formula (17). In some variations of formula (17) described in the
O
paragraphs above, in a first occurrence of Ra2 and R(,2, Ra2 and ¾2 are ·- * and the remaining occurrences of Ra2 and j)2 are as defined above for formula (17).
[451] In some variations of formula (17) described in the paragraphs above, in two occurrences of Ra2 and R^, each of Ra2 and Rb2 is H, and the remaining occurrences of Ra2 and ϊ¾2 are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in two occurrences of Ra2 and ¾2, each of Ra2 and Rj>2 is CH3, and the remaining occurrences of Ra2 and ¾2 are as defined above for formula ( 17). In some variations of formula (17) described in the paragraphs above, in two occurrences of ^ and R¾2, two of Ra2 are H, two of RM are CH3, and the remaining occurrences of Ra2 and Rb2 are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in two occurrences of
Ra2 and R(,2, Ra2 and i,2 are "¾ *" , and the remaining occurrences of A2 and Rj,2 are as defined above for formula (17), In some variations of formula ( 17) described in the paragraphs above, in
O
two occurrences of Ra2 and Rb2, Ra2 and ¾2 are '¾ and the remaining occurrences of Ra2 and i»2 are as defined above for formula (17),
[452 ] In some variations of formula (17) described in the paragraphs above, in three
occurrences of Ra2 and ¾2, each of Ra2 and ¾2 is H, and the remaining occurrences of Ra2 and Rb2 are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in three occurrences of Ra2 and Rb2, each of Ra2 and Rb2 is CH3, and the remaining occurrences of Ra2 and R 2 are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in three occurrences of Ra2 and R 2, three of R¾2 are H, three of ¾2 are C¾, and the remaining occurrences of Ra2 and Rb2 are as defined above for formula (17). In some variations of formula 17) described in the paragraphs above, in three occurrences of Ra2 and Rb2, a2 and Rb2
Figure imgf000150_0001
, and the remaining occurrences of Ra2 and Rb2 are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in three occurrences of Ra2 and R 2, Ra2 and Rb2 are
Figure imgf000150_0002
remaining occurrences of Ra2 and ¾2 are as defined above for formula (17).
[453] In some variations of formula (17) described in the paragraphs above, in four occurrences of Ra2 and R 2, each of Ra2 and Rb2 is H, and the remaining occurrences of Ra2 and R 2 are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in four occurrences of Ra2 and Rb2, each of Ra? and Rb2 is CH3, and the remaining occurrences of Ra2 and Rj,2 are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in four occurrences of Ra2 and Rb2, four of Ra2 are H, four of Rb2 are C¾, and the remaining occurrences of a2 and ¾2 are as defined above for formula (17). In some variations of formula described in the paragraphs above, in four occurrences of Ra2 and Rb2, Ra2 and Rb2 are
Figure imgf000150_0003
and the remaining occurrences of Ra2 and Rb2 are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in four occurrences of a2 and b2, Ra2 and Rb2 are
Figure imgf000150_0004
and the remaining occurrences of a2 and Rj>2 are as defined above for formula ( 17).
[454] In some variations of formula (17) described in the paragraphs above, in fi ve occurrences of Ra2 and ¾2, each of Ra2 and I½ is H, and the remaining occurrences of and Rb2 are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in five occurrences of Ra2 and R¾2, each of Ra2 and Rb2 is CH3, and the remaining occurrences of Ra2 and R 2 are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in five occurrences of Ra2 and R 2, five of ^ are H, five of Rb2 are CH3, and the remaining occurrences of Ra2 and b2 are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in five occurrences of Ra2 and Rb2, a2 and Rb2 are "^- and the remaining occurrences of Ra2 and Rb2 are as defined above for formula (17), In some variations of formula (17) described in the paragraphs above, in five occurrences of Ra2 and Rb2, ¾2 and Rb2 are
Figure imgf000151_0001
and the remaining occurrences of Ra2 and R 2 are as defined above for formula (17).
[455] In some variations of formula (17) described in the paragraphs above, in six occurrences of Ra2 and Rb2, each of Ra2 and Rb2 is H, and the remaining occurrences of R^ and Rb2 are as defined above for formula (17), In some variations of formula (17) described in the paragraphs above, in six occurrences of Ra2 and Rb2, each of Ra2 and Rb2 is CH , and the remaining occurrences of Ra2 and Rb2 are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in six occurrences of Ra2 and Rb2, six of Ra2 are H, six of Rb2 are CH3, and the remaining occurrences of Ra2 and Rb2 are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in six occurrences of
Ra2 and Rb2, ^ and R 2 are
Figure imgf000151_0002
and the remaining occurrences of Ra2 and Rb2 are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in six occurrences of Ra2 and Rb2,
Figure imgf000151_0003
and R 2 are as defined above for formula (17).
[456] In some variations of formula (17) described in the paragraphs above, in seven occurrences of Ra2 and R 2, each of Ra2 and R 2 is H, and the remaining occurrences of Ra2 and Rb2 are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in seven occurrences of and Rb2, each of Ra2 and Rb2 is CH3, and the remaining occurrences of Ra2 and Rb2 are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in seven occurrences of Ra2 and R 2, seven of Ra2 are H, seven of Rb2 are CH3, and the remaining occurrences of a and R 2 are as defined above for formula (17). In some variations of form (17) described in the paragraphs above, in seven occurrences of Ra2 and Rb2, Ra2 and Rb2 are
Figure imgf000151_0004
, and the remaining occurrences of Ra2 and R 2 are as defined above for formula (17). In some variations of formula (17) described in
O
the paragraphs above, in seven occurrences of Ra2 and Rb2, Ra2 and Rb2 are ' *· and the remaining occurrences of Ra2 and Rb2 are as defined above for formula (17). [457] In some variations of formula (17) described in the paragraphs above, in eight occurrences of Ra2 and Rb2, each of Ra2 and Rb2 is H, and the remaining occurrences of Ra2 and b2 are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in eight occurrences of Ra2 and Rb2, each of Ra2 and b2 is CH3, and the remaining occurrences of R¾2 and J¾,2 are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in eight occurrences of Ra2 and Rb2, eight of Ra2 are H, eight of R¾2 are C¾, and the remaining occurrences of Ra2 and Rb2 are as defined above for formula (17). In some variations of 7) described in the paragraphs above, in
Figure imgf000152_0001
eight occurrences of and Rb2, Ra2 and R|>2 , and the remaining occurrences of Ra2 and Rs,2 are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in eight occurrences of Ra2 and ¾2, a2 and ¾2 are
Figure imgf000152_0002
and the remaining occurrences of Ra2 and R 2 are as defined above for formula (17).
[458] In some variations of formula (17) described in the paragraphs above, in nine occurrences of a2 and b2, each of Ra2 and Rb2 is H, and the remaining occurrences of ¾2 and Rb2 are as defined above for formula (17), In some variations of formula (17) described in the paragraphs above, in nine occurrences of Ra2 and Rb2, each of Ra2 and Ri)2 is CH3, and the remaining occurrences of Ra2 and ¾ are as defined above for formula (17). In some variations of formula ( 17) described in the paragraphs above, in nine occurrences of Ra2 and Rb2, nine of R^ are H, nine of Rb2 are CH3, and the remaining occurrences of Ra2 and Rb2 are as defined above for formula (17). In some variations of formula described in the paragraphs above, in nine occurrences of a2 and b2, Ra2 and Rb2 are
Figure imgf000152_0003
, and the remaining occurrences of Ra2 and
Rb2 are as defined above for formula (17). In some variations of formula (17) described in the
O
paragraphs above, in nine occurrences ot Ra2 and Rb2, Ra2 and Rb2 are "¾ ~, and the remaining occurrences of Ra2 and Rb2 are as defined above for formula (17).
[459] In some variations of formula (17) described in the paragraphs above, in ten occurrences of Ra2 and Κ¾2, each of Ra2 and Rb2 is H, and the remaining occurrences of ^ and Κ¾2 are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in ten occurrences of Ra2 and Rb2, each of Ra2 and R¾2 is CH3, and the remaining occurrences of Ra2 and b2 are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in ten occurrences of Ra2 and Μ&2, ten of a2 are H, ten of R¾2 are CH3, and the remaining occurrences of Ra2 and ¾2 are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, in ten occurrences of
Ra2 and ¾2, a2 and ¾2 are "^- and the remaining occurrences of and I¾2 are as defined above for formul a (17). In some variations of formula (17) described in the paragraphs above, in
O
ten occurrences of and Rj>2, Ra2 and Rb2 are "¾ and the remaining occurrences of R^ and Rh2 are as defined above for formula (17).
[460] In some variations of formula (17) described in the paragraphs above, two occurrences of
Ra2 and ^ are '^- L , and the remaining occurrences of R^ and Rb2 are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, four occurrences of Ra2 and Rb2 are "^- , and the remaining occurrences of Ra2 and ¾2 are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, six occurrences of a2 and Rf,2 are "*· and the remaining occurrences of ^ and R¾2 are as defined above for formula (17). In some variations of formula (17) described in the paragraphs above, eight occurrences of a and ^ are and the remaining occurrences of Ra2 and ϊ¾>2 are as defined above for formula (17), In some variations of formula (17) described in the paragraphs above, five occurrences of a2 and ¾2 are '^- .
In some variations of formula (17) described in the paragraphs above, Dl is safratiin-O. In some variations of formula (17) described in the paragraphs above, D2 is safranin-O. In some variations of formula (17) described in the paragraphs above, D3 i s safranin-O. In some variations of formula (17) described in the paragraphs above, Dl and D2 are safranin-O. In some vari ations of formula (17) described in the paragraphs above, Dl and D3 are safranin-O. In some variations of formula (17) described in the paragraphs above, D2 and 1)3 are safranin-O.
[462] In some variations of formula (17) described in the paragraph above, the pendant phenyl ring of Dl is un substituted. In some variations of formula (17) described in the paragraph above, the pendant phenyl ring of Dl is substituted with 1-3 (e.g., 1-3, 1-2, 1, 2, or 3) electron-donating or electro -with drawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of Dl is substituted, the
substituents are selected independently from— NH2,— NHR,— NR2,— OH,— O",
— - HCOCH3,— NHCOR, - -OCH3, -----OR, ---C2H5, --R, and C„S k wherein R is C1-C6 linear or branched alkyl (e.g., C1 -C6, C 1 -C5, C1 -C4, C 1 -C3, C1 -C2, C I, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— 02,— ΙΙι , halo (e.g., F, Br, CI, I), trihaiide (e.g. ,— CF3,— CC13,— CBr3,— CI3),— CN, SO 1 I,— COOH,— COOR,— CHO, and —COR, wherein R is C1-C6 linear or branched alkyl (e.g., C 1-C6, C1-C5, C 1-C4, C 1-C3, C I - C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
[463] In some variations of formula (17) described in the two paragraphs above, the pendant phenyl ring of 1)2 is un substituted. In some variations of formula (17) described in the paragraph above, the pendant phenyl ring of D2 is substituted with 1-3 (e.g., 1-3, 1-2, I, 2, or 3) electron- donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— NH2,— IR,— NR2,— OH,— O",
— - HCOCH3,— NHCOR, --OCH3, OR, ----- C2H5,— R, and C„i k wherein R is C1-C6 linear or branched alkyl (e.g., C 1 -C6, C 1 -C5, C 1-C4, C 1 -C3, C 1-C2, CI, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— 'N02,— 'NR3 T, halo (e.g., F, Br, CI, I), trihaiide (e.g. ,— CF3, ~~CCU,— CBr3,— CI3),— CN,— SO3H,—COOH,—COOR,—CHO, and —COR, wherein R is C1 -C6 linear or branched alkyl (e.g., C 1-C6, C1 -C5, C1-C4, C 1-C3, Cl - C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
[464] In some variations of formula (17) described in the three paragraphs above, the pendant phenyl ring of D3 is unsubstituted. In some variations of formula (17) described in the paragraph above, the pendant phenyl ring of D3 is substituted with 1 -3 (e.g., 1 -3, 1-2, 1 , 2, or 3) electron- donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of D3 is substituted, the substituents are selected independently from— NH2,— NHR,— NR2,— OH,— O",
— -NHCOCH3, N I OR. OCH3, OR, --C2H5,— R, and O.i k wherein R is C1 -C6 linear or branched alkyl (e.g., C 1-C6, C 1-C5, C 1-C4, C 1-C3, C 1-C2, CI, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl ). In some embodiments in which the pendant phenyl ring of D3 is substituted, the substituents are selected independently from— N02,— R3 1, halo (e.g., F, Br, CI, I), trihaiide (e.g., {'!· =. --€<¾, --CBr3,—CI3),— CN, -- SO3H,—COOH,—COOR,—CHO, and — COR, wherein R is C1-C6 linear or branched alkyl (e.g., C 1-C6, C1-C5, C1-C4, C 1-C3, CI- C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
[465] Some cationic dye dimers fall within formula (18):
Figure imgf000155_0001
wherein each of Dl, D2, and D3 is a cationic dye moiety, n and nh independently are 0-6, and n} and itbi independently are 1-4.
[466] In some variations of formula (18), Dl, D2, and D3 are different cationic dye moieties. In some variations of formula (18), Dl , D2, and D3 are the same cationic dye moiety. In other variations of formula (18), Dl and D2 are the same cationic dye moiety and D3 is a different cationic dye moiety. In other variations of formula (18), Dl and D3 are the same cationic dye moiety and D2 is a different cationic dye moiety. In other variations of formula (18), D2 and D3 are the same cationic dye moiety and Dl is a different cationic dye moiety. In some variations of formula ( 18), each of Dl, D2, and D3 independently is selected from the group consisting of safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavme, and methylene blue.
[467] In some variations of formula (18) described in the paragraphs above, n is 0-6, 0-5, 0-4, 0-3, 0-2, 0-1, 1-6, 1 -5, 1-4, 1 -3, 1-2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, 5-6, 0, 1, 2, 3, 4, 5, or 6.
[468] In some variations of formula (18) described in the paragraphs above, nb is 0-6, 0-5, 0-4, 0-3, 0-2, 0-1, 1-6, 1-5, 1-4, 1-3, 1-2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, 5-6, 0, 1, 2, 3, 4, 5, or 6.
[469] In some variations of formula (18) described in the paragraphs above, nj is 1-4, 1-3, 1-2, 2-4, 2-3, 3-4, 1 , 2, 3, or 4,
[470] In some variations of formula (18) described in the paragraphs above, nbl is 1-4, 1-3, 1-2, 2-4, 2-3, 3-4, 1 , 2, 3, or 4, [471] In some variations of formula (18) described in the paragraphs above, 1)1 is safranin-O. In some variations of formula (18) described in the paragraphs above, D2 is safranin-O. In some variations of formula (18) described in the paragraphs above, D3 is safranin-O. In some variations of formula (18) described in the paragraphs above, Dl and D2 are safranin-O. In some variations of formula (18) described in the paragraphs above, Dl and D3 are safranin-O. In some variations of formula (18) described in the paragraphs above, D2 and D3 are safranin-O.
[472] In some variations of formula (18) described in the paragraph above, the pendant phenyl ring of Dl is unsubstituted. In some variations of formula (18) described in the paragraph above, the pendant phenyl ring of Dl is substituted with 1-3 (e.g., 1-3, 1-2, 1, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— -NH2,— NHR,— NR2,— OH,— O",
— NHCOCH3,— NHCOR, --OCH3,—OR, --C2H5,— R, and C,,l k wherein R is C1-C6 linear or branched alkyl (e.g., C1-C6, C 1-C5, C1-C4, C 1-C3, C1-C2, C I , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— -N02,— -N 3 +, halo (e.g., F, Br, CI, I), trihalide (e.g.,— CF3,— CCI3,— CBr3,— CI3),— CN,— SO3H,—COOH,— COOR,— CHO, and — COR, wherein R is C1-C6 linear or branched al kyl (e.g., C 1 -C6, C1-C5, C 1 -C4, C 1 -C3, C l- C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
[473 ] In some variations of formula (18) described in the two paragraphs above, the pendant phenyl ring of D2 is unsubstituted. In some variations of formula (18) described in the paragraph above, the pendant phenyl ring of D2 is substituted with 1-3 (e.g., 1-3, 1 -2, 1, 2, or 3) electron- donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— NH2,— NHR,— NR2,— OH,— O",
NHCOCH3,— -NHCOR, --OCH3,—OR,— C2H5,— R, and (\j k wherein R is C1-C6 linear or branched alkyl (e.g., C1-C6, C 1-C5, C1-C4, C 1-C3, C 1-C2, C I, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— -N02,— -NR3 +, halo (e.g., F, Br, CI, I), trihalide (e.g.,— CF3,— CCI3,— CBr3,— CI3),— CN, --SO3H, COOH,—COOR,— -CHO, and — COR, wherein R is C1-C6 linear or branched alkyl (e.g., C 1 -C6, C1-C5, C 1 -C4, C 1-C3, CI- C2, CI , C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-
C6, C5, or C6 linear or branched alkyl).
[474] In some variations of formula (18) described in the three paragraphs above, the pendant phenyl ring of D3 is unsubstituted. In some variations of formula (18) described in the paragraph above, the pendant phenyl ring of D3 is substituted with 1-3 (e.g., 1 -3, 1-2, 1, 2, or 3) electron- donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of D3 is substituted, the substituents are selected independently from— -NH2,— NHR,— NR2,— OH,— O",
— NHCOCH3,— HCOR,— OCH3,—OR,— C2H5,— R, and— C6¾, wherein R is C1-C6 linear or branched alkyl (e.g., C1-C6, C1-C5, C1-C4, C1-C3, C1-C2, CI , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl ). In some embodiments in which the pendant phenyl ring of 1)3 is substituted, the substituents are selected independently from— -NO2,— - R3 +, halo (e.g., F, Br, CI, I), trihaiide (e.g.,— CF3,— CCI3,— CBr3,— CI3),— CN,— SO3H,— COOH,— COOR,— CHO, and — COR, wherein R is C1-C6 linear or branched alkyl (e.g., C1-C6, C1-C5, C1-C4, C 1-C3, Cl- C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
Some cationic dye dimers fall within formula (19):
Figure imgf000157_0001
wherein each of Dl, D2, and D3 is a cationic dye moiety, n} and nb} independently are 0-5, and «2 and Hb2 independently are 1-5,
[476] In some variations of formula (19), Dl, D2, and D3 independently are selected from the group consisting of safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue. In some variations of formula (19), Dl and D2 are different cationic dye moieties. In other variations of formula (19), Dl and D2 are the same cationic dye moiety. [477] In some variations of formula (19) described in the paragraphs above, n} is 0-5, 0-4, 0-3, 0-2, 0-1, 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, I, 2, 3, 4, or 5.
[478] In some variations of formula (19) described in the paragraphs above, ηι,ι is 0-5, 0-4, 0-3,
0- 2, 0-1, 1 -5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1, 2, 3, 4, or 5,
[479] In some variations of formula (19) described in the paragraphs above, n2 is 1-5, 1-4, 1 -3,
1- 2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, I, 2, 3, 4, or 5.
[480] In some variations of formula (19) described in the paragraphs above, nb2 is 1-5, 1-4, 1- 3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, I, 2, 3, 4, or 5.
[481] In some variations of formula (19) described in the paragraphs above, 1)1 is safranin-O. In some variations of formula (19) described in the paragraphs above, D2 is safranin-O. In some variations of formula (19) described in the paragraphs above, D3 is safranin-O. In some variations of formula (19) described in the paragraphs above, Dl and D2 are safranin-O. In some variations of formula (19) described in the paragraphs above, Dl and D3 are safranin-O. In some variations of formula (19) described in the paragraphs above, D2 and D3 are safranin-O.
[482] In some variations of formula (19) described in the paragraph above, the pendant phenyl ring of Dl is unsubstituted. In some variations of formula (19) described in the paragraph above, the pendant phenyl ring of Dl is substituted with 1-3 {e.g., 1-3, 1-2, 1, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of Dl is substituted, the
substituents are selected independently from— -NH2,— NHR,— NR2,— OH,— O",
— NHCOCH3,— HCOR,— OCH3,—OR,— C2H5,— R, and— C&¾, wherein R is C1-C6 linear or branched alky! {e.g., C1-C6, C1-C5, C1-C4, C1-C3, C1-C2, CI , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— -NO2,— - R3 +, halo {e.g., F, Br, CI, I), trihalide {e.g.,— CF3,— CCI3,— CBr3,— CI3),— CN,— SO3H,— COOH,— COOR,— CHO, and — COR, wherein R is C1-C6 linear or branched alkyl {e.g., C 1 -C6, C1-C5, C1 -C4, C1-C3, Cl- C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
[483] In some variations of formula (19) described in the two paragraphs above, the pendant phenyl ring of D2 is unsubstituted. In some variations of formula (19) described in the paragraph above, the pendant phenyl ring of 1)2 is substituted with 1-3 (e.g., 1-3, 1 -2, 1, 2, or 3) electron- donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— NH2,— -NHR,— -NR2,— OH,— O",
— NHCOCH3,— HCOR, ΟΠ I : .— OR,— C2H5,— R, and G.l k wherein R is C1-C6 linear or branched alkyl (e.g., C1 -C6, C 1 -C5, C1-C4, C 1 -C3, C1-C2, C I, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— N02,— NR3 +, halo (e.g., F, Br, CI, I), trihaiide (e.g., CF3, --CCI3, --CBr3, --CI3),— CN, - - SO3H, --COOH,—COOR,—CHO, and — COR, wherein R is C 1-C6 linear or branched alkyl (e.g., C 1-C6, C1-C5, C 1-C4, C 1-C3, Cl- C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
[484] In some variations of formula (19) described in the three paragraphs above, the pendant phenyl ring of D3 is unsubstituted. In some variations of formula (19) described in the paragraph above, the pendant phenyl ring of D3 is substituted with 1-3 (e.g., 1-3, 1 -2, 1, 2, or 3) electron- donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of D3 is substituted, the substituents are selected independently from— NH2,— -NHR,— NR2,— OH,— O",
— HCOCH3, -—NHCOR,— OCH3,— OR,— C2H5,— , and— C6H5, wherein R is C 1-C6 linear or branched alkyl (e.g., C1 -C6, C 1 -C5, C1 -C4, C 1 -C3, C1 -C2, C I, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of D3 is substituted, the substituents are selected independently from— 02,— ΝΙ^ , halo (e.g., F, Br, CI, I), trihaiide (e.g.,— CF3,— CCI3,— CBr3,— CI3),— CN, SO 1 1,— COOH,— COOR,— CHO, and —COR, wherein R is C1-C6 linear or branched alkyl (e.g., C 1-C6, C1-C5, C 1-C4, C 1-C3, Cl - C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
Some cationic dye trimers fall within formula (20):
Figure imgf000160_0001
^β) , in which each of Dl and D2 is a cationic dye moiety, n; and ribi independently are 0-5 and n2 and nb2 independently are 1-5.
[486] In some variations of formula (20), each ofDl, D2, and D3 independently is selected from the group consisting of safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue. In some variations of formula (20), Dl, D2, and D3 are different cationic dye moieties. In some variations of formula (20), Dl, D2, and D3 are the same cationic dye moiety. In other variations of formula (20), Dl and D2 are the same cationic dye moiety and D3 is a different cationic dye moiety. In other variations of formula (20), Dl and D3 are the same cationic dye moiety and D2 is a different cationic dye moiety. In other variations of formula (20), D2 and D3 are the same cationic dye moiety and Dl is a different cationic dye moiety.
[487] In some variations of formula (20) described in the paragraphs above, n} is 0-5, 0-4, 0-3,
0- 2, 0-1, 1 -5, 1-4, 1 -3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1, 2, 3, 4, or 5 ,
[488] In some variations of formula (20) described in the paragraphs above, n2 is 1-5, 1-4, 1-3,
1 - 2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5.
[489] In some variations of formula (20) described in the paragraphs above, i is 0-5, 0-4, 0-3,
0- 2, 0-1, 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1, 2, 3, 4, or 5.
[490] In some variations of formula (20) described in the paragraphs above, nh2 is 1 -5, 1.-4, 1-3,
1- 2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, I, 2, 3, 4, or 5.
[491] In some variations of formula (20) described in the paragraphs above, Dl is safranin-O. In some variations of formula (20) described in the paragraphs above, D2 is safranin-O. In some variations of formula (20) described in the paragraphs above, D3 is safranin-O. In some variations of formula (20) described in the paragraphs above, Dl and D2 are safranin-O. In some variations of formula (20) described in the paragraphs above, Dl and D3 are safranin-O. In some variations of formula (20) described in the paragraphs above, D2 and D3 are safranin-O. [492] In some variations of formula (20) described in the paragraph above, the pendant phenyl ring of Dl is unsubstituted. In some variations of formula (20) described in the paragraph above, the pendant phenyl ring of Dl is substituted with 1-3 (e.g., 1 -3, 1-2, 1 , 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— -NH2,— NHR,— NR2,— OH,— O",
— - NHCOCH3,—NHCOR,— OCH3,—OR,— C2H5,— R, and C-j k wherein R is C 1-C6 linear or branched alky! (e.g., C 1-C6, C 1-C5, C1-C4, C 1-C3, C1-C2, CI , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— N02,— R3 , halo (e.g., F, Br, CI, I), trihalide (e.g. , --CF3, CCU ---CBr3,— CI3),— CN, --SO3H, --COOH, --COOR,— CHO, and — COR, wherein R is C1-C6 linear or branched alkyl (e.g., C 1 -C6, C 1-C5, C1 -C4, C 1-C3, C l- C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched aikyi ).
[493] In some variati ons of formula (20) described in the two paragraphs above, the pendant phenyl ring of D2 is unsubstituted. In some variations of formula (20) described in the paragraph above, the pendant phenyl ring of D2 is substituted with 1-3 (e.g., 1-3, 1-2, I, 2, or 3) electron- donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— -NH2,— NHR,— NR2,— OH,— O",
--NHCOCH3,— -NHCOR, --OCH3,—OR,— C2H5,— R, and C,,l k wherein R is C1-C6 linear or branched alkyl (e.g., C1-C6, C 1-C5, C1-C4, C 1-C3, C1-C2, C I , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— -N02,— -NR3 +, halo (e.g., F, Br, CI, I), trihalide (e.g. ,— CF3,— CCI3,— CBr3,— CI3),— CN,— SO3H,— COOH,— COOR,— CHO, and — COR, wherein R is C1.-C6 linear or branched al kyl (e.g., C I -C6, C1-C5, C I -C4, C 1 -C3, C l- C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
[494] In some variations of formula (20) described in the three paragraphs above, the pendant phenyl ring of D3 is unsubstituted. In some variations of formula (20) described in the paragraph above, the pendant phenyl ring of D3 is substituted with 1-3 (e.g., 1-3, 1 -2, 1, 2, or 3) electron- donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of D3 is substituted, the substituents are selected independently from— H2,— NHR,— R2,— OH,— O",
— ICOCH3, X I li OR. (X I k—OR,— C2H5,— R, and G,i k wherein R is C 1-C6 linear or branched aikyi (e.g., C 1-C6, C 1-C5, C 1-C4, C 1-C3, C1-C2, CI , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched aikyi ). In some embodiments in which the pendant phenyl ring of D3 is substituted, the substituents are selected independently from— NO?,— NR3 , halo (e.g., F, Br, CI, I), trihalide (e.g. ,— CF3, --CCI3, ---CBr3,— CI3),— CN, SO ;! !, --COOH, --COOR,— CHO, and — COR, wherein R is C 1-C6 linear or branched alkyl (e.g. , C 1-C6, C 1-C5, C1-C4, C 1-C3, C l- C2, CI , C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched aikyi).
Some cationic dye trimers fall within formula (21);
Figure imgf000162_0001
> , in which each of Dl, D2, and D3 is a cationic dye moiety, n} and /¾/ independently are 0-5 and n2 and nh2 independently are 1-5.
[496] In some variations of formula (21), Dl, D2, and D3 are different cationic dye moieties. In some variations of formula (21 ), Dl , 1)2, and D3 are the same cationic dye moiety. In other variations of formula (21), Dl and D2 are the same cationic dye moiety and D3 is a different cationic dye moiety. In other variations of formula (21), Dl and D3 are the same cationic dye moiety and D2 is a different cationic dye moiety. In other variations of formula (21 ), D2 and D3 are the same cationic dye moiety and Dl is a different cationic dye moiety. In some variations of formula (21 ), each of Dl, D2, and D3 independently is selected from the group consisting of safranin-O, toiuidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue.
[497] In some variations of formula (21 ) described in the paragraphs above, ni is 0-5, 0-4, 0-3, 0-2, 0-1, 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1, 2, 3, 4, or 5.
[498] In some variations of formula (21) described in the paragraphs above, n2 is 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5 , [499] In some variations of formula (21) described in the paragraphs above, % is 0-5, 0-4, 0-3,
0- 2, 0-1, 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1, 2, 3, 4, or 5.
[500] In some variations of formula (21) described in the paragraphs above, ni,2 is 1-5, 1-4, 1 -3,
1- 2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, I, 2, 3, 4, or 5.
[501] In some variations of formula (21) described in the paragraphs above, Dl is safranin-O. In some variations of formula (21) described in the paragraphs above, D2 is safranin-O. In some variations of formula (21) described in the paragraphs above, D3 is safranin-O. In some variations of formula (21) described in the paragraphs above, Dl and D2 are safranin-O. In some variations of formula (21 ) described in the paragraphs above, 1)1 and D3 are safranin-O. In some variations of formula (21) described in the paragraphs above, D2 and D3 are safranin-O.
[502] In some variations of formula (21) described in the paragraph above, the pendant phenyl ring of Dl is unsubstituted. In some variations of formula (21) described in the paragraph above, the pendant phenyl ring of Dl is substituted with 1-3 (e.g., 1 -3, 1-2, 1 , 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of Dl is substituted, the
substituents are selected independently from— M k— NHR,— NR2,— OH,— O",
— NHCOCH3,—NHCOR,— OCH3,—OR,— C2H5,— R, and C-j k wherein R is C 1-C6 linear or branched alky! (e.g., C 1-C6, C 1-C5, C1-C4, C 1-C3, C1-C2, CI , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched aikyi). In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— N02,— R3 , halo (e.g., F, Br, CI, I), trihalide (e.g.,— CF3,— CCI3,— CBr3, (' ! : )..— CN, SO : I f .— COOH,— COOR,— CHO, and — COR, wherein R is C1-C6 linear or branched alkyl (e.g., C 1 -C6, C 1-C5, C1 -C4, C 1-C3, C l- C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched aikyi ).
[503] In some variati ons of formula (21) described in the two paragraphs above, the pendant phenyl ring of D2 is unsubstituted. In some variations of formula (21 ) described in the paragraph above, the pendant phenyl ring of D2 is substituted with 1-3 (e.g., 1-3, 1-2, I, 2, or 3) electron- donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— -NH2,— NHR,— NR2,— OH,— O",
— HCOCH3,— HCOR,— OCH3,—OR,— C2H5,— , and— C&¾, wherein R is C 1-C6 linear or branched alkyl (e.g., C1 -C6, C 1 -C5, C1 -C4, C 1 -C3, C1 -C2, C I, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— 02,— ΝΙΙι , halo (e.g., F, Br, CI, I), trihaiide (e.g. ,— CF3,— CCi3,— CBr3, ('! =},— CN, SO 1 I,— COOH,— COOR,— CHO, and —COR, wherein R is C1-C6 linear or branched alkyl (e.g., C 1-C6, C1-C5, C 1-C4, C 1-C3, C I - C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
I] In some variations of formula (21) described in the three paragraphs above, the pendant phenyl ring of 1)3 is un substituted. In some variations of formula (21) described in the paragraph above, the pendant phenyl ring of D3 is substituted with 1-3 (e.g., 1-3, 1-2, I, 2, or 3) electron- donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of D3 is substituted, the substituents are selected independently from— NH2,— IR,— NR2,— OH,— O",
— - HCOCH3,— NHCOR, --OCH3, OR, ----- C2¾,— R, and C„i k wherein R is C1-C6 linear or branched alkyl (e.g., C 1 -C6, C 1 -C5, C 1-C4, C 1 -C3, C 1-C2, CI, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of D3 is substituted, the substituents are selected independently from— 'N02,— 'NR3 T, halo (e.g., F, Br, CI, I), trihaiide (e.g. ,— CF-i, ~~CCU,— CBr3,— CI3),— CN,— S03H,—COOH,—COOR,—CHO, and —COR, wherein R is C1 -C6 linear or branched alkyl (e.g., C 1-C6, C1 -C5, C1-C4, C 1-C3, Cl - C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
[505] Some cationic dye trimers fall within formula (22):
Figure imgf000164_0001
, in which each of Dl, D2, and D3 is a cationic dye moiety, nj, n2, nl and nbj independently are 1-5.
[506] In some variations of formula (22), Dl, D2, and D3 are different cationic dye moieties. In some variations of formula (22), Dl , D2, and D3 are the same cationic dye moiety. In other variations of formula (22), Dl. and D2 are the same cationic dye moiety and D3 is a different cationic dye moiety. In other variations of formula (22), Dl and D3 are the same cationic dye moiety and D2 is a different cationic dye moiety. In other variations of formula (22), D2 and D3 are the same cationic dye moiety and Dl is a different cationic dye moiety. In some variations of formula (22), each of Dl, D2, and D3 independently is selected from the group consisting of safranin-O, toiuidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue.
[507] In some variations of formula (22) described in the paragraphs above, iti is 1 -5, 1-4, 1 -3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5.
[508] In some variations of formula (22) described in the paragraphs above, n2 is 1 -5, 1-4, 1 -3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5.
[509] In some variations of formula (22) described in the paragraphs above, nn is 1.-5, 1 -4, 1 -3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5.
[510] In some variations of formula (22) described in the paragraphs above, nbi is 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5.
[511] In some variations of formula (22) described in the paragraphs above, Dl is safranin-O. In some variations of formula (22) described in the paragraphs above, D2 is safranin-O. In some variations of formula (22) described in the paragraphs above, D3 is safranin-O. In some variations of formula (22) described in the paragraphs above, Dl. and D2 are safranin-O. In some variations of formula (22) described in the paragraphs above, Dl and D3 are safranin-O. In some variations of formula (22) described in the paragraphs above, D2 and D3 are safranin-O.
[512] In some variations of formula (22) described in the paragraph above, the pendant phenyl ring of Dl is unsubstituted. In some variations of formula (22) described in the paragraph above, the pendant phenyl ring of Dl is substituted with 1-3 {e.g., 1-3, 1 -2, 1, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of Dl is substituted, the
substituents are selected independently from— H2,— HR,— NR2,— OH,— O",
NHCOCI k,— -NHCOR, OCj h OR, --C2H5,—R, and (\j k wherein R is C1-C6 linear or branched aikyi {e.g., C 1-C6, C 1-C5, C1-C4, C 1-C3, C 1-C2, C I, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched aikyi). In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— -N02,— -N 3 +, halo (e.g., F, Br, CI, I), trihalide (e.g.,— CF3,— CC13,— CBr3,— CI3),— CN,— S03H, -COOH,— COOR,— CHO, and — COR, wherein R is C1-C6 linear or branched alkyl (e.g., C 1-C6, C1-C5, C1-C4, C 1-C3, Cl- C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
[513 ] In some variations of formula (22) described in the two paragraphs above, the pendant phenyl ring of D2 is unsubstituted. In some variations of formula (22) described in the paragraph above, the pendant phenyl ring of 1)2 is substituted with 1-3 (e.g., 1-3, 1 -2, 1, 2, or 3) electron- donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of 1)2 is substituted, the substituents are selected independently from— NH2,— HR,— R2,— OH,— O",
--NHCOCH3,— -NHCOR, --OCH3,—OR, --C2H5,—R, and G,l k wherein R is C1-C6 linear or branched alkyl (e.g., C1 -C6, C 1 -C5, C1-C4, C 1 -C3, C1-C2, C I, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— N02,— NR3 +, halo (e.g., F, Br, CI, I), trihalide (e.g., CF3, --CCI3, --CBr3, --CI3),— CN, --SO3H, COO I i, COOR. CHO, and —COR, wherein R is C 1-C6 linear or branched alkyl (e.g., C 1-C6, C1-C5, C 1-C4, C 1-C3, Cl- C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
[514] In some variations of formula (22) described in the three paragraphs above, the pendant phenyl ring of D3 is unsubstituted. In some variations of formula (22) described in the paragraph above, the pendant phenyl ring of D3 is substituted with 1-3 (e.g., 1-3, 1 -2, 1, 2, or 3) electron- donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of D3 is substituted, the substituents are selected independently from— NH2,— -NHR,— -NR2,— OH,— O",
— NHCOCH3,—NHCOR,— OCH3,—OR,— C2H5,— , and— C6H5, wherein R is C 1-C6 linear or branched alkyl (e.g., C1 -C6, C 1 -C5, C1 -C4, C 1 -C3, C1 -C2, C I, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of D3 is substituted, the substituents are selected independently from— N02,— NR3 +, halo (e.g., F, Br, CI, I), trihalide (e.g.,— CF3,— CCI3,— CBr3,— CI3),— CN, SO I i, COOH, COOR. CHO, and —COR, wherein R is C1-C6 linear or branched alkyl (e.g., C 1-C6, C1-C5, C 1-C4, C 1-C3, Cl - C2, CI , C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-
C6, C5, or C6 linear or branched alkyl).
[515] Some cationic dye trimers fall within formula (23):
Figure imgf000167_0001
in which each of Dl, D2, and D3 is a cationic dye moiety and n and nb independently are 1-6,
[516] In some variations of formula (23), Dl, D2, and D3 are different cationic dye moieties. In some variations of formula (23), Dl, D2, and D3 are the same cationic dye moiety. In other variations of formula (23), Dl and D2 are the same cationic dye moiety and D3 is a different cationic dye moiety. In other variations of formula (23), Dl and D3 are the same cationic dye moiety and D2 is a different cationic dye moiety. In other variations of formula (23), D2 and D3 are the same cationic dye moiety and Dl is a different cationic dye moiety. In some variations of formula (23), each of Dl, D2, and D3 independently is selected from the group consisting of safranin-O, toiuidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue.
[517] In some variations of formula (23) described above, n is 1-6, 1-5, 1-4, 1-3, 1-2, 2-6, 2-5, 12-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, 5-6, 1, 2, 3, 4, 5, or 6.
[518] In some variations of formula (23) described above, nb is 1-6, 1-5, 1-4, 1-3, 1-2, 2-6, 2-5, 12-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, 5-6, 1, 2, 3, 4, 5, or 6,
[519] In some variations of formula (23) described in the paragraphs above, Dl is safranin-O. In some variations of formula (23) described in the paragraphs above, D2 is safranin-O. In some variations of formula (23) described in the paragraphs above, D3 is safranin-O. In some variations of formula (23) described in the paragraphs above, Dl and D2 are safranin-O. In some variations of formula (23) described in the paragraphs above, Dl. and D3 are safranin-O. In some variations of formula (23) described in the paragraphs above, D2 and D3 are safranin-O. [520] In some variations of formula (23) described in the paragraph above, the pendant phenyl ring of Dl is unsubstituted. In some variations of formula (23) described in the paragraph above, the pendant phenyl ring of Dl is substituted with 1-3 (e.g., 1 -3, 1-2, 1 , 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— -NH2,— NHR,— NR2,— OH,— O",
— NHCOCH3,—NHCOR,— OCH3,—OR,— C2H5,— R, and C-j k wherein R is C 1-C6 linear or branched alky! (e.g., C 1-C6, C 1-C5, C1-C4, C 1-C3, C1-C2, CI , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— N02,— R3 , halo (e.g., F, Br, CI, I), trihalide (e.g. , --CF3, CCU ---CBr3,— CI3),— CN, --SO3H, --COOH, --COOR,— CHO, and — COR, wherein R is C1-C6 linear or branched alkyl (e.g., C 1 -C6, C 1-C5, C1 -C4, C 1-C3, C l- C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched aikyi ).
[521] In some variati ons of formula (23) described in the two paragraphs above, the pendant phenyl ring of D2 is unsubstituted. In some variations of formula (23) described in the paragraph above, the pendant phenyl ring of D2 is substituted with 1-3 (e.g., 1-3, 1-2, I, 2, or 3) electron- donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— -NH2,— NHR,— NR2,— OH,— O",
--NHCOCH3,— -NHCOR, --OCH3,—OR,— C2H5,— R, and C,,l k wherein R is C1-C6 linear or branched alkyl (e.g., C1-C6, C 1-C5, C1-C4, C 1-C3, C1-C2, C I , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— -N02,— -NR3 +, halo (e.g., F, Br, CI, I), trihalide (e.g. ,— CF3,— CCI3,— CBr3,— CI3),— CN,— SO3H,— COOH,— COOR,— CHO, and — COR, wherein R is C1.-C6 linear or branched al kyl (e.g., C I -C6, C1-C5, C I -C4, C 1 -C3, C l- C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
[522] In some variations of formula (23) described in the three paragraphs above, the pendant phenyl ring of D3 is unsubstituted. In some variations of formula (23) described in the paragraph above, the pendant phenyl ring of D3 is substituted with 1-3 (e.g., 1-3, 1 -2, 1, 2, or 3) electron- donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of D3 is substituted, the substituents are selected independently from— H2,— NHR,— R2,— OH,— O",
— ICOCH3, X I li OR. (X I k—OR,— C2H5,— R, and G,i k wherein R is C 1-C6 linear or branched aikyi (e.g., C 1-C6, C 1-C5, C 1-C4, C 1-C3, C1-C2, C I , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched aikyi ). In some embodiments in which the pendant phenyl ring of D3 is substituted, the substituents are selected independently from— NO?,— NR3 , halo (e.g., F, Br, CI, I), trihalide (e.g. ,— CF3, --CCI3, ---CBr3,— CI3), --CN, SO ;! !, --COOH, --COOR, --CHO, and — COR, wherein R is C 1-C6 linear or branched alkyl (e.g., C 1-C6, C 1-C5, C1-C4, C 1-C3, C l- C2, CI , C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched aikyi).
Some cationic dye mul timers fall within formula (24):
Figure imgf000169_0001
, in which m is 2; each of Dl, a first D2, and a second D2 is a cationic dye moiety; h and S2 independently are 1 -4; ring A is aryl, heteroaryl,
cycloaikyi, or heterocyciyl; for each independent instance of Raj and
Figure imgf000169_0002
Rai and RM (1)
Q independently are H or CH3, or (2) ai and R¾i are '¾ or "¾ , or (3) two of C ai j,i are '^- L ; and, for each independent instance of Ra2 and Rj>2; ^ and Rt>2 (1) independently are H or CH3, or (2) Ra2 and j,2 are " or ·"?. or (3) two of C a2 b2 are "¾ ¾ .
[524] In some variations of formula (24), Dl, the first 1)2, and the second D2 are different cationic dye moieties. In some variations of formula (24), Dl, the first D2, and the second D2 are the same cationic dye moiety. In other variations of formula (24), Dl and the first D2 are the same cationic dye moiety and the second D2 is a different cationic dye moiety. In other variations of formula (24), Dl and the second D2 are the same cationic dye moiety and the first D2 is a different cationic dye moiety. In other variations of formula (24), the first D2 and the second D2 are the same cationic dye moiety and Dl is a different cationic dye moiety. In some variations of formula (24), each of 1)1 , the first D2, and the second 1)2 independently is selected from the group consisting of safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue.
[525] In some variations of formula (24), is 1-4, 1-3, 1-2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[526] In some variations of formul a (24) described in the paragraphs above, ? is 1-4, 1-3, 1-2, 2-4, 2-3, 3-4, 1 , 2, 3, or 4.
[527] In some variations of formul a (24) described in the paragraphs above in which / is 1, Rai and Rjji are both H. In some variations of formula (24) described in the paragraphs above in which / is 1, Raj is H and R&j is CH3. In some variations of formula (24) described in the paragraphs above in which is 1 , Rai and M are both CH3. In some variations of formula (24) described in the paragraphs above in which l is 1, Rai and Rw are ' V¾Si . In some variations of
O
formula (24) described in the paragraphs above in which l} is 1, Raj and &j are "^- \
[528] In variations of formula (24) described in the paragraphs above in which h is 2, the two instances of Ra and Rb are indicated as ai and M and Ra2 and Rj,?, respectively. In some variations of formula (24) described in the paragraphs above in which h is 2, each of Rai and ¾i and Ra2 and Rj,2 is H. In some variations of formula (24) described in the paragraphs above in which // is 2, each of aj and &j and
Figure imgf000170_0001
is CH3. In some variations of formula (24) described in the paragraphs above in which is 2, each of Rai and Ra2 is H and each of Rbi and Rb2 is CH3. In some variations of formula (24) described in the paragraphs above in which // is 2, each of Rai, Ra2, and Rm is H and R 2 is CH3.
[529] In some variations of formula (24) described in the paragraphs above in which lj is 2, each of Rai and RM is H and Ra2 and ¾2 are "¾ . In some variations of formula (24) described in the paragraphs above in which lj is 2, each of Rai and R¾i is H and Ra2 and Rt,2 are O
A · ^c . In some variations of f ormula (24) described in the paragraphs above in which lj is 2, each of Rai and j,i is CH3 and R^ and j)2 are '¾ ^ . In some variations of formula (24) described in the paragraphs above in which is 2, each of Rai and R¾i is Q¾ and Ra2 and Rj>2
Figure imgf000171_0001
are
In some variations of formula (24) described in the paragraphs above in which is 2, Rai is H, is (Ί f and Ra2 and R 2 are '¾ . In some variations of formula (24) described in the
O
paragraphs above in which U is 2, Rai is H, i is CH3, and Ra2 and ¾2 are '¾· f" . In some variations of formula (24) described in the paragraphs above in which h is 2, Ra! and i and
Ra2 and R¾2 together are 1 . In some variations of formula (24) described in the paragraphs above in which /2 is 2, Rai and R
Figure imgf000171_0002
. In some variations of formula (24) described in the paragraphs above in which l} is 2, Rai and 1(i are ^4- ^ ^ and
O
Rb2 are - ^ . In some variations of formula (24) described in the paragraphs above in which li
O O
is 2, ai and ¾i are ^ and 2 are "¾·
[530] In variations of formula (24) described in the paragraphs above in which is 3, the three instances of Ra and Rb are indicated as ai and i; Ra2 and R*->2; and A3 and Rj,3, respectively. In some variations of formula (24) described in the paragraphs above in which I is 3 , In some variations of formula (24) described in the paragraphs above in which l} is 3, each of Rai,Rbi, Ra2, R¾2, a3, and bs is H. In some variations of formula (24) described in the paragraphs above in which 1} is 3 , each of Rai, Rbi, Ra2, Rb2, Ra3, and ^ is CH3. In some variations of formula (24) described in the paragraphs above in which Ij is 3 , each of Rai,Rbi, R_ , and ½, is H and each of Ra3 and ^ is CH3. In some variations of formula (24) described in the paragraphs above in which / is 3 , each of Rai,Rj,t, Ra2, and R 2, is CH3 and each of ^ and Rj,3 is H. In some variations of formula (24) described in the paragraphs above in which Ij is 3 , Rai is H and each of Ra2, A3, Rbi , 2, and B3 is CH3. In some variations of formula (24) described in the paragraphs above in which Ij is 3 , each of Ral and Ra2 is H and each of Raj, Rbi, *2, and 3 is CH3. In some variations of formula (24) described in the paragraphs above in which is 3 , each of Rai, Ra2, and 33 is H and each of Rbi, Rb2, and bs is (Ί \ . [531] In some variations of formula (24) described in the paragraphs above in which l} is 3, each of Rai,¾i, Ra2, and J¾,2, is H and a3 and ¾3 are w "¾ . In some variations of formula (24) described in the paragraphs above in which l} is 3, each of Rai,Rbi, a2, and Rj>2, is CH3 and Ra3 and Rb3 are "^- . In some variations of formula (24) described in the paragrap above in which is 3, Rai is H and each of Ra2, Rj,i, and Rb2 is CH3, and Ra3 and Ri)3 are
Figure imgf000172_0001
. in some variations of formula (24) described in the paragraphs above in which lj is 3, each of Rai and Ra2 is H and each of RM and ¾2 is CH3, and A3 and Rj,3 are
Figure imgf000172_0002
[532] In some variations of formula (24) described in the paragraphs above in which l} is 3,
O
each of Rai,Rbi, Ra2, and j,?, is H and R^ and Rj,3 are . In some variations of formula (24) described in the paragraphs above in which lj is 3, each of R i,Rbi, Ra2, and R^, s CH3 and Ra3
O
and j>3 are ^\ In some variations of formula (24) described in the paragraphs above in which
O
// is 3, Rai is H and each of R^, Rbj, and Rj,2 is C¾, and and Rb3 are '¾· ** , In some variations of formula (24) described in the paragraphs above in which ij is 3, each of Rai and Ra2
O
is H and each of Rbi and ¾2 is CH3, and as and Rb3 are "^- ^\
[533] In some variations of formula (24) described in the paragraphs above in which l} is 3, Ral and Rw are '¾ ?~ , Ra2 and b2 are '¾ , and each of and R!)3 is H. In some variations of formula (24) described in the paragraphs above in which h i s 3, Rai and R¾i are "¾ ** , Ra2 and Rj,2 are "¾ , and each of Raj and s^ is CH3. In some variations of formula (24) described in the paragraphs above in which /2 is 3, Rai and ¾ι are "¾ Ra2 and ¾2 are '¾ , ^ is H, and Rb3 is ( I f ;. In some variations of formula (24) described in the paragraphs above in which 1} i s 3, Rai and R i are "^- , Ra2 and R|>2 are '¾ and each of as and R s is H. In some variations of formula (24) described in the paragraphs above in which h is 3, ai and i are la
(24) d
Figure imgf000173_0001
are
"¾ , Raj is H, and Rh3 is C¾.
[534] In some variations of formula (24) described in the paragraphs above in which / is 3, Rai and ¾i are
Figure imgf000173_0002
and each of and j>3 is H. In some variations of formula (24) described in the paragraphs above in which is 3, Rai and R i are '¾· , Ra2 and
Figure imgf000173_0003
O
the paragraphs above in which l} is 3, ai and M are "¾ ^\ RA2 and 2 are 5 , ^ is H, and Rb3is CH3. In some variations of formula (24) described in the paragraphs above in which //
O
is 3, Rai and R¾i are '¾ ^\ Ra2 and Rs,2are '¾· f", and each of R¾3 and ^i Ii In some variations of formula (24) described in the paragraphs above in which i} is 3, Ra! and ¾j are
¾¾ O
"^- a2 and Rb2areA '¾· and each of A3 and b3is CH3. In some variations of formula
(24) described in the paragraphs above in which / is 3, RaJ and M are "^- Ra2 and b2 are O
Figure imgf000173_0004
[535] In some variations of formula (24) described in the paragraphs above in which l} is 3, Rai
O O
and bi are ¾ ** A· f <*", Ra2 and 2are ¾ '¾A· and each of R¾3 and ji H. In some variations of
O
formula (24) described in the paragraphs above in which h is 3, Rai and R¾i are f\ Ra2 and b2 are
Figure imgf000173_0005
of A3 and b3 is CH3. In some variations of formula (24) described in the paragraphs above in which i} is 3, Ral and ¾ι are
Figure imgf000173_0006
and Rbsis CH3. In some variations of formula (24) described in the paragraphs above in which
O O
is 3, Rai and ¾i are *" , Ra2 and Rb2 are "»- and each of ¾3 and Rb3 is H. In some variations of formula (24) described in the paragraphs above in which l} is 3, Rai and R¾i are O O
-\ and Rb2 are and each of and Rb3 is CH3. In some variations of formula (24)
O O
described in the paragraphs above in which // is 3, Ra} and are "*· , Ra2 and i,2 are '¾· ¾ ,
Figure imgf000174_0001
[536] In some variations of formula (24) described in the paragraphs above in which i} is 3, Rai and RM and Ra2 and Rj>2 together are - and each of RA3 and .b3 is H. In some variations of formula (24) described in the paragraphs above in which lj is 3, ai and M and Ra2 and Rb2 together are ^ ^i^ anc each of Ra3 and R^is CH3. In some variations of formula (24) described in the paragraphs above in which / is 3, Rai and RM and Ra2 and Rj,2 together are V V
, Ra3 is H, and ^ is CH3. In some variations of formula (24) described in the paragraphs above in which // is 3, Ra3 and M and a2 and R¾,2 together are and Ra3 and i,3 are
'¾ . In some variations of formula (24) described in the paragraphs above in which is 3, ai
O
and M and Ra2 and ¾2 together are <· and a3 and R¾3 are <- .
[537] In variations of formula (24) described in the paragraphs above in which ¾ is 4, the three instances of Ra and j, are indicated as Rai and ; Ra2 and Rj,2; as and Rj,3; and 34 and R¾4, respectively. In some variations of formula (24) described in the paragraphs above in which l} is 4, In some variations of formula (24) described in the paragraphs above in which lj is 4, each of Rai,¾i, ¾2, ¾2, ¾3, ¾3, Ra4, and M is H. In some variations of formula (24) described in the paragraphs above in which l} is 4, each of Raj,Rt>i, 2, 2, as, R&3, A4, and ¾4 is CH3. In some variations of formula (24) described in the paragraphs above in which l} is 4, each of Rai, M, Ra2, Rb2, a3, and &sis H and each of A4 and MIS CH3. In some variations of formula (24) described in the paragraphs above in which h is 4, each of Rai, M, a2, and Rj,2is H and each of Ra3, Rb3; RA4. and ^is CH3. In some variations of formula (24) described in the paragraphs above in which h is 4, each of Rai, , Ra2, ¾>2, a3, and ¾3is CH3 and each of RA4 and jrfis H. [538] In some variations of formula (24) described in the paragraphs above in which l} is 4, each of Rai,Ra2, and Ra3 is H and each of w, Rb2, and j,3 is CH3. In some variations of formula (24) described in the paragraphs above in which is 4, Raj is H, M is CH3, and each of Ra2, ¾2, Ra3. and RB3 is CH3. In some variations of formula (24) described in the paragraphs above in which lj is 4, Rai is H, R1(i is CH3, and each of R^, R¾2, Ra3, and ¾3 is Ii In some variations of formula (24) described in the paragraphs above in which l} is 4, each of Rai and a2 i s H, each of RM and RB2 is CH3, and each of and j,3 is H. In some variations of formula (24) described in the paragraphs above in which i} is 4, each of Rai and is H, each of Rm and Rb2 is CH3, and each of A3 and &3 is CH3.
[539] In some variations of formula (24) described in the paragraphs above in which I} is 4, Rai and RM are H, Ra2 and ϊ¾2 are H, Ra3 and R1(3 are H, and Ra4 and Rb are '¾ . In some variations of formula (24) described in the paragraphs above in which is 4, Ral and RM are H,
Ra2 and are H, Ra3 and Rb3 are CH3, and A4 and Rb4 are "¾ . In some variations of formula (24) described in the paragraphs above in which l} is 4, aj and R¾i are H, ^ and ¾2 are CH3, as and ¾3 are CH3, and RA4 and &4 are " L . In some variations of formula (24) described in the paragraphs above in which ; is 4, Rai and M are CH3, Ra2 and ¾2 are CH3,
Ra3 and Rj,3 are CH3, and A and RM are '¾· ^ ,
[540] In some variations of formula (24) described in the paragraphs above in which / is 4, as and Rbj are H, ^ and Rb2 are H, Ra3 and &3 are '^- , and Ra4 and (,4 are "^- . In some variations of formula (24) described in the paragraphs above in which lj is 4, Rai and R¾i are I:
Ra2 and Rb2 are CH3, Ra3 and j,3 are
Figure imgf000175_0001
. In some variations of formula (24) described in the paragraphs above in which l} is 4, ai and ¾i are CH3, Ra2 and b2 are CH3, RA3 and RM are "¾ , and RA4 and I¾4 are '¾ . In some variations of formula (24) described in the paragraphs above in which lj is 4, RAI is H, M is CH3, RA2 and ^ are
CI I3, Ra3 and j,3 are and Ra and ¾ are " *· . In some variations of formula (24) described in the paragraphs above in which is 4, Rai is H, R¾i is CH3, Ra2 is H, ¾ is CH3, RA3 and j,3 are
Figure imgf000176_0001
[541] In some variations of formula (24) described in the paragraphs above in which l} is 4, Rai
Figure imgf000176_0002
and Rj>i are H, Ra2 and j>2 are , aj and 3 are "¾ <* and Ra4 and 4 are '¾ . In some vari ations of formula (24) described in the paragraphs above in which lj is 4, Rai and ¾i are CH3, ^ and Rb2 are "¾ , RA3 and Ε*3 are "¾ , and RA4 and are "*· . In some variations of formula scribed in the paragraphs above in which lj is 4, Rai is H, is
CH3, Ra2 and ¾2 are
Figure imgf000176_0003
as and R 3 are '¾· and Ra4 and R|>4 are . In some variations of formula (24) described in the paragraphs above in which ; is 4, ai and M are
. _ w
"¾ Ra2 and b2 are '¾ Ra3 and j,3 are "^- ^\ and RA and j,4 are '¾ ^\
[542] In some variations of formula (24) described in the paragraphs above in which !j is 4, Rat
O
and Rbi are H, R^ and j,2 are H, Ra3 and ¾3 are H, and RA4 and j,4 are ^ . In some vari ations of formula (24) described in the paragraphs above in which is 4, aj and 1(j are H,
O
Ra2 and j,2 are H, Ra3 and j,3 are CH3, and Ra4 and M are A · ^c-* . In some variations of formula (24) described in the paragraphs above in which ; is 4, ai and M are H, Ra2 and (,2
O
are CH3, ^ and j,3 are CH3, and Ra4 and R 4 are · . In some variations of formula (24) described in the paragraphs above in which // is 4, Ra} and j are CH3, Ra2 and ¾ are CH3,
A-
Ra3 and RM are CH3, and 34 and b4 are .
[543] In some variations of formula (24) described in the paragraphs above in which lj is 4, ai
O
and bi are H, R^ and RB2 are H, Ra3 and ¾3 are and Ra4 and B4 are v. In some variations of formula (24) described in the paragraphs above in which ij is 4, RAL and w are H,
A A
Ra2 and Rb2 are CH, as and *,3 are "¾· and RA4 and b4 are In some variations of formula (24) described in the paragraphs above in which is 4, Rai and ¾ι are CH3, Ra2 and
O O
2 are CH3, Ra3 and ¾ are "^- and A4 and ¾4 are ^\ In some variations of formula (24) described in the paragraphs above in which lj is 4, RAI is H, ¾ι is C¾, Ra2 and ¾2 are
Figure imgf000177_0001
described in the paragraphs above in which / is 4, RAJ is H, R¾i is CH3, Ra2 is H, ¾2 is CH3, Ra3
O O
and Rj,3 are ¼ "^A- ^\ and Rai and RM are ¼ · ^(\
[544] In some variations of formula (24) described in the paragraphs above in which i} is 4, Rai
0 0 o
and R[»i are H, Ra2 and .b2 are'^ Ra3 and R¾3 are and RA4 and M are' 4- ^\ In some variations of formula (24) described in the paragraphs above in which l} is 4, Rai and ¾i are
0 0 o
CH , Ra2 and ¾>2 are A / Ra3 and s,3 are % and Ra4 and j,4 are A ¾ . In some variations of formula (24) described in the paragraphs above in which is 4, Rai is H, Rbi is
0 0 o
CH , Ra2 and ¾>2 are'¾A Ra3 and R¾3 are "¾ A and A4 and RM are "¾A ^\ In some variations
0 of formula (24) described in the paragraphs above in which l} is 4, Rai and M are ¾ ' -A , Ra2 and R¾2 are
Figure imgf000177_0002
.
[545] In some variations of formula (24) described in the paragraphs above in which / is 4, Rai
*T 7 O and j,i are Ra2 and ϊ¾>2 are H, aj and Rb3 are H, and a4 and ^ are "^- In some variations of formula (24) described in the paragraphs above in which h is 4, Raj and &j are
'¾ r " , Ra2 and Rj>2 are CH3,
Figure imgf000177_0003
and R1(3 are CH3, and Ra4 and Rb4 are ¾ A· / In some variations of formula (24) described in the paragraphs above in which Jj is 4, Rai and Rbl are
Figure imgf000177_0004
Ra2
O
and j>2 are H, Ra3 and Rj>3 are CH3, and Ra4 and j,4 are . [546] In some variations of formula (24) described in the paragraphs above in which l} is 4, Rai and Rbi are
Figure imgf000178_0001
In some variations of formula (24) described in the paragraphs above in which // is 4, Rai and RM
Q are <*\ Ra2 and 3½ are ^\ Ra3 and Rb3 are CH3, and Ra4 and Rb4 are · f\ In some variations of formula (24) described in the paragraphs above in which l} is 4, Rai and Rb! are
Figure imgf000178_0002
Ri3 and RM are CH3, and Ra and Rb are '¾· In some variations of formula (24) described in the paragraphs above in which l} is 4, Ra! and R()i are
Figure imgf000178_0003
Ra2 and Rb2 are Ra3 and R!)3 are H, and Ra and Rb4 are f 547] In some variations of formula (24) described in the paragraphs above in which l} is 4, Rai and Rbi are
Figure imgf000178_0004
. [548] In some variations of formula (24) described in the paragraphs above in which i is 4, Rai and Rj,] are '¾ Ra2 and R 2 are "¾ <*\ Ra3 and Rb3 are H, and Ra4 and Rb4 are · f\ In some variations of formula (24) described in the paragraphs above in which is 4, Rai and R l are
Figure imgf000178_0005
In some variations of formula (24) described in the paragraphs above in which is 4, ai and R i are
Figure imgf000178_0006
In some variations of formula 24 described in the ara ra hs above in which / is 4 RaJ and RM are
Figure imgf000178_0007
[549] In some variations of formula (24) described in the paragraphs above in which // is 4,
Figure imgf000178_0008
and R i are [550] In some variations of formula (24) described in the paragraphs above in which l} is 4, Rai and ¾i are
Figure imgf000179_0001
In some variations of formula (24) described in the paragraphs above in which h i s 4, ai and R¾i are 0 0 o
A Α A
'¾· Ra2 and Rb2 are Ra3 and Rb3 are CH3, and Ra4 and Rj>4 are ^ . In some variations of formula (24) described in the paragraphs above in which lj i s 4, Ra! and Rb! are 0 0 o
¾A ¾·^·
Ra2 and Rb2 are '^- Ra3 and Rb3 are CH3, and Ra4 and Rb4 are r\ In some variations of formula (24) described in the paragraphs above in which l} is 4, Ra! and Rb! are 0 0 o
< , Ra2 and Rb2 are ' *· Ra3 and ¾3 are H, and Ra4 and Rb4 are '¾· f\
[551] In some variations of formula (24) described in the paragraphs above in which l} is 4, Rai and Rbi are
Figure imgf000179_0002
.
[552] In some variations of formula (24) described in the paragraphs above in which i is 4, Rai and Rbi are H, and Rb2 are H, and Ra3 and Rb3 and Ra4 and Rb4 together are "^- . In some variations of formula (24) described in the paragraphs above in which l} is 4, Ral and Rbi are H, R^ and Rb2 are CH3, and Ra3 and Rb3 and Ra4 and RM together are '^- x . In some variations of formula (24) described in the paragraphs above in which ; is 4, ai and Ra2 are H,
Rbi and Rb2 are CH3, and Ra3 and Rb3 and Ra4 and Rb4 together are "*· [553] In some variations of formula (24) described in the paragraphs above in which l} is 4, ai
• 5S
and bi are H, R^ and Rb2 are '¾ ^\ and Ra3 and Rb3 and Ra4 and Rb4 together are ν¾· . In some variations of formula (24) described in the paragraphs above in which / is 4, Ral and bi
Figure imgf000179_0003
, Ra2 and Rb2 are CH3, and Ra3 and Rb3 and Ra4 and RM together are ' L x . In some variations of formula (24) described in the paragraphs above in which l} is 4, Rai is H, bi is
CH3, Ra2 and Rb2 are '¾ and Ra3 and R 3 and Ra4 and Rb4 together are ^ . [554] In some variations of formula (24) described in the paragraphs above in which l} is 4, Rai
O
and ¾i are H, Ra2 and R 2 are ¼ A and RA3 and R 3 and RA4 and R 4 together are ¾ . In some variations of formula (24) described in the paragraphs above in which h is 4, Rai and Rbi
O
are A Ra2 and Rb2 are CH3, and Ra3 and Rb3 and Ra4 and RM together are "^- . In some variations of formula (24) described in the paragraphs above in which I} i s 4, Ra! is H, Rb{ i s
O
CH3, Ra2 and Rb2 are · and RA3 and RB3 and Ra4 and Rb4 together are ¾ .
[555] In some variations of formula (24) described in the paragraphs above in which i} is 4, Rai
Figure imgf000180_0001
In some variations of formula 24) described in the paragraphs above in which i} is 4, Raj and
Rbi
Figure imgf000180_0002
. In some variations of formula (24) described in the paragraphs above in which is 4, Rai and Rbi O O
are % -A ^ , Ra2 and Rb2 are ¾A , and A3 and R 3 and RA4 and B4 together are ¾^ Y V
[556] In some variations of formula (24) described in the paragraphs above in which h is 4, Rai and M are L Ra2 and Rb2 are '¾ and as and R 3 and Ra4 and Rb4 together are
[557] In some variations of formula (24) described in the paragraphs above in which h is 4, Ral and jji and Ra2 and R 2 together are ' '- and aj and Rb3 and A4 and B4 together are
[558] In some variations of formula (24) described in the paragraphs above in which /? is 1, Rai and j>i are both H. In some variations of formula (24) described in the paragraphs above in which l2 is I, ai is H and Rbi is CH3. In some variations of formula (24) described in the paragraphs above in which l2 is 1, Rai and Rbi are both CI-I3. In some variations of formula (24) described in the paragraphs above in which l2 is 1, Rai and bi are . In some variations of
O
formula (24) described in the paragraphs above in which l2 is 1 , ai and R¾i are ^\
[559] In variations of formula (24) described in the paragraphs above in which ¾ is 2, the two instances of Ra and ¾ are indicated as Rai and bi and Ra2 and ¾2, respectively. In some variations of formula (24) described in the paragraphs above in which l2 is 2, each of Rai and M and Ra2 and R|,2 is H. In some variations of formula (24) described in the paragraphs above in which l2 is 2, each of Rai and R i and ^ and ¾2 is CH3. In some variations of formula (24) described in the paragraphs above in which l? is 2, each of Rai and Ra2 is H and each of j,t and Rb2 is CH3. In some variations of formula (24) described in the paragraphs above in which l2 is 2, each of Ra{, Ra2, and bi is H and Rb2 is CH3.
[560] In some variations of formula (24) described in the paragraphs above in which l2 is 2, each of Rai and RM is H and and Rb2 are '¾ , In some variations of formula (24) described in the paragraphs above in which l2 is 2, each of Rai and ¾i is H and Ra2 and Rb2 are O
. In some variations ot formula (24) described in the paragraphs above in which l2 is 2, each of ai and bi is CH3 and Ra2 and Rb2 are "¾ . In some variations of formula (24) described in the paragraphs above in which l2 is 2, each of Rai and R¾i is Q¾ and and Rb2 O
are ·- ^ .
In some variations of formula (24) described in the paragraphs above in which l2 i s 2, Rai is H, )l is CII3, and Ra2 and Rb2 are "¾ , jn some variations of formula (24) described in the
O
paragraphs above in which l2 is 2, Rai is H, Rbi is CH3, and Ra2 and Rb2 are ¾ '¾· . In some variations of formula (24) described in the paragraphs above in which l2 is 2, Ra! and Rb! and
Ra2 and Rb2 together are "L . described in the paragraphs above in which /? is 2, Rai and Rb
Figure imgf000181_0001
. In some variations of formula (24) described in the paragraphs above in which is 2, Ral and ¾i are "^- Ra2 and O
Rj,2 are ' *· ^\ In some variations of formula (24) described in the paragraphs above in which l2
O O
is 2, Rai and Rbi are and Ri)2 are ^ .
[561] In variations of formula (24) described in the paragraphs above in which l2 is 3, the three instances of Ra and R¾ are indicated as Rai and Rbi; a2 and R^; and aj and Ry, respectively. In some variations of formula (24) described in the paragraphs above in which is 3, In some variations of formula (24) described in the paragraphs above in which l2 i s 3, each of Rai,Rbi, a2, ¾)2, a3, and Rjtf is H. In some variations of formula (24) described in the paragraphs above in which l2 is 3, each of R i,Rbi, Ra2, ¾2, Ra3, and ^ i CH3. In some variations of formula (24) described in the paragraphs above in which l2 is 3, each of Rai,Rw, Ra2, and b2, is H and each of a3 and ^ is CH3. In some variations of formula (24) described in the paragraphs above in which l2 is 3, each of Rai,Rbi, ¾2, and j,2, is CH3 and each of Ra3 and
Figure imgf000182_0001
is H. In some variations of formula (24) described in the paragraphs above in which l2 is 3, aj is H and each of Ra2, Raj, bi, ¾2, and s is CH3. In some variations of formula (24) described in the paragraphs above in which !.? is 3, each of Rai and Ra2 is H and each of Ra3, RM, ¾2, and R|,3 is CH3. In some variations of formula (24) described in the paragraphs above in which l2 is 3, each of Ra{, Ra2, and a3 is H and each of i, 2, and 3 is CH3.
[562] In some variations of formula (24) described in the paragraphs above in which l2 is 3, each of Rai,Rbi, Ra2, and Rt,2, is H and ^ and ¾ are '¾ . In some variations of formula (24) described in the paragraphs above in which l2 is 3, each of Rai,Rbi, a2, and b2, is CH3 and Ra3 and Rb3 are " . In some variations of formula (24) described in the paragraphs above in which l2 is 3, Rai is H and each of Ra2, Rbi, and Rb2 is CH3, and a and are ^ . In some variations of formula (24) described in the paragraphs above in which l2 is 3, each of Rai and Ra2
.s
is H and each of Rbi and ¾j is CH3, and as and &3 are
[563] In some variations of formula (24) described in the paragraphs above in which l2 is 3,
O
each of Rai,Rbi, Ra2, and b?, is H and R^ and b3 are . In some variations of formula (24) described in the paragraphs above in which l2 is 3, each of Rai,Rbi, Ra2, and Rb2, is CH3 and Ras O
and R ? are . In some variations of formula (24) described in the paragraphs above in which
O
h is 3, Rai is H and each of R^, Rbi, and ¾2 is CH3, and and Rb3 are , In some variations of formula (24) described in the paragraphs above in which l2 is 3, each of Rai and Ra2 is H and each of bi and Rb2 is CH , and Ra3 and Rb3 are
Figure imgf000183_0001
[564] In some variations of formul described in the paragraphs above in which l2 is 3, Ral and Rj,i a
Figure imgf000183_0002
, and each of and Rb3 is H. In some variations of formula (24) described in the paragraphs above in which l2 is 3, Raj and R¾i are '¾ , Ra2 and R 2 are "¾ , and each of aj and Rs^ is CH3. In some variations ot formula (24) described in the paragraphs above in which 2 is 3, Rai and Rbi are "¾ Ra2 and Rb2 are '¾ , R^ is H, and Rb3 is ( I f ;. In some variations of formula (24) described in the paragraphs above in which l2 is 3, Rai and Rbi are "^- , Ra2 and R 2 are ^ , and each of Ra3 and Rb3 is H. In some variations of formula (24) described in the paragraphs above in which l2 is 3, Ra! and Rb! are
"¾ ^ , a2 and Rb2 are "% , and each of as and b3 is CH3. In some variations of formula
(24) described in the paragraphs above in which h is 3, RaJ and bi are "¾ *" , Ra2 and R 2 are
Figure imgf000183_0003
[565] In some variations of formula (24) described in the paragraphs above in which l2 is 3, Ral
— Ύ ^
and R i are "¾ , Ra2 and Rb2 are , and each of ^ and b3 is H. In some variations of formula (24) described in the paragraphs above in which l2 is 3, ai and bi are "¾ Ra2 and
Figure imgf000183_0004
some variations of formula (24) described in
18: „—-j o the paragraphs above in which l2 is 3, Rai and M are "¾ Ra2 and Rb2 are "*· 5 , ^ is H, and Rb3 is CH3. In some variations of formula (24) described in the paragraphs above in which l2
O
is 3, Rai and R¾i are '¾ ^\ Ra2 and Rs,2 are '¾· f" , and each of Ra3 and Rs,3 is H. In some variations of formula (24) described in the paragraphs above in which l2 is 3, Ral and w are
O
a2 and Rb2 are X , and each of Ra3 and b3 is CH3. In some variations of formula
(24) described in the paragraphs above in which l2 is 3, Rai and Rw are "^- , Ra2 and j,2 are
Figure imgf000184_0001
[566] In some variations of formula (24) described in the paragraphs above in which l2 is 3, Rai
O O
and Rbi are U *¾·-U f\ Ra2 and R^ are ¼ '¾A , and each of Ra3 and b3 is H, In some variations ot
O
formula (24) described in the paragraphs above in which l2 is 3, Rai and R¾i are ^\ Ra2 and j,2 are
Figure imgf000184_0002
of A3 and b3 is CH3. In some variations of formula (24) described in the paragraphs above in which l2 is 3, Ral and ¾i are
Figure imgf000184_0003
, is H, and Rb3 is ( I f ;. In some variations of formula (24) described in the paragraphs above in which l2
O 0
is 3, ai and 1(i are **A */" , Ra2 and ¾2 are ¾ '¾Α· / and each of R¾3 and ¾3 is H. In some variations of formula (24) described in the paragraphs above in which h is 3, Rai and ¾i are
Figure imgf000184_0004
described in the paragraphs above in which l2 is 3, Ral and M are
Figure imgf000184_0005
Figure imgf000184_0006
[567] In some variations of formula (24) described in the paragraphs above in which l2 is 3, Rat and bi and Ra2 and !½ together are and each of Ra3 and ϊ¾3 is H. In some variations of formula (24) described in the paragraphs above in which l2 is 3, Rai and bi and ^ and ¾2 together are and each of Ra3 and R 3 is CH3. In some variations of formula (24) described in the paragraphs above in which l2 is 3, Rai and I¾i and Ra2 and Rb2 together are
RA3 is H, and ¾3 is CH3. In some variations of formula (24) described in the paragraphs above in which l2 is 3, Rai and ¾i and and ¾2 together are '*· 1 , and Ra3 and Rb3 are
" *· . In some variations of formula (24) described in the paragraphs above in which l2 is 3, Rai
9
and Rjji and Ra2 and Rb2 together are ^ and R and Rt>3 are .
[568] In variations of formula (24) described in the paragraphs above in which l2 is 4, the three instances of Ra and Rb are indicated as Ral and !¾; Ra2 and Rb2; Ra3 and Rb3; and Ra4 and R¾4, respectively. In some variations of formula (24) described in the paragraphs above in which l2 is 4, In some variations of formula (24) described in the paragraphs above in which l2 is 4, each of Rai,Rbj, Ra2, jj2, as, i,3. A4, and Rb4 is H. In some variations of formula (24) described in the paragraphs above in which l2 is 4, each of Rai,Rbi, R^, Rb2, R33, R¾3, RA4, and M is CH3. In some variations of formula (24) described in the paragraphs above in which l2 is 4, each of Rai, ex, Ra2, R¾2, A , and Rb3 is H and each of A4 and b4 is CH3. In some variations of formula (24) described in the paragraphs above in which l2 is 4, each of Rai, M, Ra2, and Rb2 is H and each of Ra3, ¾3, Ra ; and ^ is CH3. In some variations of formula (24) described in the paragraphs above in which l2 is 4, each of Rai, R*i, Ra2, R*2, A3, and Rb3 is CH3 and each of Ra and Rb4 is H.
[569] In some variations of formula (24) described in the paragraphs above in which l2 is 4, each of Rai,Ra2, and A3 is H and each of Rj,i, ¾2, and B3 is CH3. In some variations of formula (24) described in the paragraphs above in which l2 is 4, Rai is H, Rbi i s CH3, and each of Ra2, ¾2, Ra3. and Rb3 is CH3. In some variations of formula (24) described in the paragraphs above in which l2 is 4, Rai is H, R1(i is CH3, and each of ^, R¾2, 33, and R¾3 is H. In some variations of formula (24) described in the paragraphs above in which h is 4, each of Rai and Ra2 is H, each of w and Rb2 is CH3, and each of as and R|>3 is H. In some variations of formula (24) described in the paragraphs above in which l2 is 4, each of Rai and a? is H, each of Rbi and Rb2 is CH3, and each of Ra3 and Rb3 is CH3.
[570] In some variations of formula (24) described in the paragraphs above in which /? is 4, Rai and Rbi are H, ^ and Rb2 are H, Ra3 and Rw are H, and Ra4 and Rb4 are "¾ . In some variations of formula (24) described in the paragraphs above which l2 i s 4, ai and R i are H,
R¾2 and R¾2 are H, Ra3 and ¾3 are CH3, and RA4 and RM are
Figure imgf000186_0001
. In some variations of formula (24) described in the paragraphs above in which l2 is 4, Ra! and Ι¾ι are H, Ra2 and are CH3, Raj and b3 are CH3, and Ra4 and Rb4 are "^- . In some variations of formula (24) described in the paragraphs above in which l2 is 4, Rai and bi are CH3, a2 and ¾2 are CH3,
Ra3 and ¾3 are CH3, and Ra4 and RM are '¾ ,
[571] In some variations of formula (24) described in the paragraphs above in which /? is 4, Rai and bi are H, R^ and R¾2 are H, Ra3 and Rb3 are "^- and A4 and Rb are ^ , In some variations of formula (24) described in the paragraphs above in which /? is 4, ai and RM are H,
RA2 and b2 are CH3, Ra3 and Rj,3 are
Figure imgf000186_0002
. In some variations of formula (24) described in the paragraphs above in which l2 i s 4, Raj and Rbi are CH3, Ra2 and
¾>2 are CH3, Ra3 and t,3 are and Ra4 and RM are ^ . In some variations of formula 24) described in the paragraphs above in which l2 is 4, Rai is H, RM is CH3, Ra2 and R 2 are
CH3, a3 and ¾3 are "¾ ^\ and Ra4 and R¾4 are "^- . In some variations of formula (24) described in the paragraphs above in which l2 is 4, Rai is H, Rbi is CH3, 32 is H, ¾2 is CH3, Ra3
Figure imgf000186_0003
and Rj,3 are .
[572 ] In some variations of formula (24) described in the paragraphs above in which /? is 4, Rai and Rbi are H, R^ and R¾2 are " V¾Si Ra3 and Rb3 are ' V¾-%£ and Ra4 and Rj)4 are ' V¾ Si . In some variations of formula (24) described in the paragraphs above in which l2 is 4, Raj and Rbi are CH3, Ra2 and b2 are " V¾Si Ra3 and Rb3 are Hi and Ra and Rj,4 are S ^£\ In some variations of formula (24) described in the paragraphs above in which l2 s 4, Raj is H, Rbi i s
Figure imgf000186_0004
CH3, 32 and b2 are "*· RA and R1(3 are , In some variations of formula (24) described in the paragraphs above in which l2 is 4, Ra! and Rt>i an are Ra3 and Rb3 are X , and Ra4 and Rb4 are [573] In some variations of formula (24) described in the paragraphs above in which l2 is 4, Rai p
and ¾i are H, Ra2 and ¾2 are H, Ra3 and ¾3 are H, and Ra4 and I¾ are ¼ "*A· . In some variations of formula (24) described in the paragraphs above in which l2 is 4, Rai and R¾i are H,
O
Ra2 and Rb2 are H, Ra3 and j,3 are CH3, and Ra4 and Ri i are "^- . In some variations of formula (24) described in the paragraphs above in which l2 is 4, Ra! and j,j are H, R^ and Rb2
O
are CH3, R^ and ¾3 are CH3, and Ra-i an RM are '¾· , In some variations of formula (24) described in the paragraphs above in which l2 is 4, Rai and w are CH3, Ra2 and ¾ are CH3, A3 and ¾3 are CH3, and A4 and R¾4 are
Figure imgf000187_0001
[574] In some variations of formula (24) described in the paragraphs above in which l2 is 4, Rai
O
and Rbi are H, Ra2 and i,2 are H, Ra3 and ¾>3 are '¾· , and Ra4 and Rb4 are v. In some variations of formula (24) described in the paragraphs above in which l2 i s 4, ai and R i are H,
O O
%A %A
Ra2 and (,2 are CH3, Ra3 and Rb3 are and A4 and &4 are ^\ In some variations of formula (24) described in the paragraphs above in which l2 i s 4, ai and R i are CH3, Ra2 and
O O
Rb2 are CH3, Ra3 and ^ are '¾· and A4 and ¾4 are ^\ In some variations of formula (24) described in the paragraphs above in which /? is 4, Rai is H, ¾i is CH3, Ra2 and ¾2 are
CH3, Ra3 and Rj,3 are
Figure imgf000187_0002
In some variations of formula (24) described in the paragraphs above in which !? is 4, RaJ is H, R¾i is C¾, Ra2 is H, ¾2 is CH3, A3
Figure imgf000187_0003
[575] In some variations of formula (24) described in the paragraphs above in which l2 is 4, Raj and i»i are H, Ra2
Figure imgf000187_0004
some variations of formula (24) described in the paragraphs above in which l2 is 4, ai and ¾i are
0 0 o
¾A A A
CH3, Ra2 and ¾2 are ^\ Ra3 and ¾3 are ^\ and Ra4 and Rb4 are ¾ . In some variations of formula (24) described in the paragraphs above in which l2 is 4, ai is H, Rbi is
0 0 o
('! . Rai and ¾2 areA Ra3 and Rb3 are ¾ i and Ra4 and RM are Α In some variations
O
of tormula (24) described in the paragraphs above in which l2 is 4, Rai and M are - A2 and Rb2 are
Figure imgf000188_0001
[576] In some variations of formula (24) described in the paragraphs above in which l2 is 4, Ras — y O and RM are "^- ^*, A2 and ^ are H, and R1(3 are H, and RA4 and t,4 are *"¾· In some variations of formula (24) described in the paragraphs above in which l2 is 4, Ra! and w are
O
"¾ Ra2 and R¾2 are CH3, and RM are CH3, and 34 and ¾4 are f\ In some variations ot formula (24) described in the paragraphs above in which l2 is 4, RaJ and RbJ are '¾ , Ra2
O
and Rj,2 are H, Ra3 and j,3 are CH3, and RA4 a d Rj>4 are ¾ ' 1A ^ ,
[577] In some variations of formula (24) described in the paragraphs above in which l2 is 4, Raj
~7 v™7 O and Rbi are ^ Ra2 and Rj,2 are "Q Ra3 and R1(3 are H, and Ra4 and Rb4 are A· In some variations of formula (24) described in the paragraphs above in which l2 is 4, Ral and M are " .¾ - , Ra2 and RB2 are
Figure imgf000188_0002
In some variations of formula (24) described in the paragraphs above in which l2 is 4, ai and ¾i are
Figure imgf000188_0003
. In some variations of formula (24) described in the paragraphs above in which l2 is 4, Rai and Rbi are
" ¾¾ , Ra2 and Rh2 are " ¾ , Ra3 and j,3 are H, and Ra4 and M are
Figure imgf000188_0004
.
[578] In some variations of formula (24) described in the paragraphs above in which /? is 4, Rai and RM are
Figure imgf000188_0005
[579] In some variations of formula (24) described in the paragraphs above in which l2 is 4, Raf
O O
and Rw are " Ra2 and Rb2 are Ra3 and Rb3 are H, and Ra4 and R 4 are ■■ f\ In some vari ations of formula (24) described in the paragraphs above in which h is 4, Rai and ¾ι are Ra2 and Rb2 are
Figure imgf000189_0001
In some variations of formula (24) described in the paragraphs above in which l2 i s 4, Rai and Rb! are
Figure imgf000189_0002
In some variations of formula (24) described in the paragraphs above in which l2 is 4, Ra! and Rb! are
Figure imgf000189_0003
In some variations of formula (24) described in the paragraphs above in which l is 4, Rai
Figure imgf000189_0004
[581] In some variations of formula (24) described in the paragraphs above in which /? is 4, Rai and Rbi are
Figure imgf000189_0005
In some variations of formula (24) described in the paragraphs above in which l2 is 4, Rai and R¾i are
Figure imgf000189_0006
In some variations of formula (24) described in the paragraphs above in which /? is 4, Ral and i are
Figure imgf000189_0007
In some vari ations of formula (24) described in the paragraphs above in which l2 is 4, Ral and RM are
Figure imgf000189_0008
.
[582] In some variations of formula (24) described in the paragraphs above in which l2 is 4, Ra{ and RM are
Figure imgf000189_0009
[583] In some variations of formula (24) described in the paragraphs above in which l2 is 4, Rai and ¾i are H, Ra2 and Rj>2 are H, and Ras and R^ and RA4 and Rt>4 together are ¾ . In some variations of formula (24) described in the paragraphs above in which l2 is 4, Ral and RbJ are II, ^ and R^ are CH3, and Raa and ^ and RA and M together are " <~ . in some variations of formula (24) described in the paragraphs above in which l2 is 4, aj and Ra2 are H,
Rex and j,2 are (Ί f and as and j,3 and A4 and R¾4 together are x .
[584] In some variations of formula (24) described in the paragraphs above in which l2 is 4, Rai and j,i are H, ^ and ^ are
Figure imgf000190_0001
and RA3 and j,3 and A and R together are x ^ , In some variations of formula (24) described in the paragraphs above in which l2 is 4, and ¾ι
Figure imgf000190_0002
, Ra2 and j,2 are CH3, and A3 and j,3 and A4 and ¾4 together are - . In some variations of formula (24) described in the paragraphs above in which l2 is 4, Rai is H, ^i is
Figure imgf000190_0003
CI¾, Ra2 and &2 are " N^
[585] In some variations of formula (24) described in the paragraphs above in which l2 is 4, ai
O
and Rbi are H, a2 and ^ are '¾· and R^ and ¾3 and Ra4 and t,4 together are . In some variations of formula (24) described in the paragraphs above in which l2 is 4, ai and I¾i O
are ' <■ ¾ , Ra2 and s,2 are CH3, and A3 and Rj,3 and Ra4 and M together are '<· . In some variations of formula (24) described in the paragraphs above in which l2 is 4, Rai is H, is
O
CHj, Ra2 and Rj,2 are and Ra3 and Rb3 and Ra4 and ^ together are x .
[586] In some variations of formula (24) described in the paragraphs above in which l2 is 4, Rai
O O
and j>i are a2 and ¾2 are '¾· and ^ and j,? and Ra4 and Rt>4 together are 'x . In some vari ations of formula (24) described in the paragraphs above in whi ch /? is 4, Rai and
O ¾—
bi are ' 1 ^ , R^ and ϊ¾>2 are and A and R¾3 and Ra4 and R¾4 together are 1. In some variations of formula (24) described in the paragraphs above in which /? is 4, Rai and ¾i are
Figure imgf000191_0001
and a3 and ¾3 and Ra4 and ¾4 together are
[587] In some variations of formula (24) described in the paragraphs above in which h is 4, Ral and R[»i a
Figure imgf000191_0002
and j,2 are , and R^ and ¾3 and 34 and ^ together are
[588] In some variations of formula (24) described in the paragraphs above in which h is 4, Ra{ and R[»i and Ra2 and Rj>2 together are - and Raj and R1(j and a4 and R^ together are
[589] In some variations of formula (24) described in the paragraphs above, ring A is
(a) ' " 8 ,
Figure imgf000191_0003
optionally substituted with halo or C 1-C6 linear or branched alkyl;
Figure imgf000191_0004
optionally substituted with halo or C 1-C6 linear or branched alkyl; or
Figure imgf000191_0005
Figure imgf000192_0001
optionally substituted with halo or C1 -C6 linear or branched alkyl.
[590] In some variations of formula (24) described in the paragraphs above, ring A is substituted with halo. In some variations, the halo is F, Br, I, or Ci.
[591] In some variations of formula (24) described in the paragraphs above, ring A is substituted with C1 -C6 linear or branched alkyl (e.g., C 1-C6, C1-C5, C1 -C4, C1 -C3, C1-C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5 C6, C5, or C6 linear or branched alkyl). [592] In some variations of formula (24) described in the paragraphs above, 1)1 is safranin-O. In some variations of formula (24) described in the paragraphs above, the first D2 is safranin-O. In some variations of formula (24) described in the paragraphs above, the second D2 is safranin- O. In some variations of formula (24) described in the paragraphs above, Dl and the first D2 are safranin-O. In some variations of formula (24) described in the paragraphs above, Dl and the second D2 are safranin-O. In some variations of formula (24) described in the paragraphs above, the first D2 and the second D2 are safranin-O.
[593] In some variations of formula (24) described in the paragraph above, the pendant phenyl ring of Dl is unsubstituted. In some variations of formula (24) described in the paragraph above, the pendant phenyl ring of Dl is substituted with 1-3 (e.g., 1 -3, 1-2, 1 , 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— -NH2,— NHR,— NR2,— OH,— O",
— NHCOCH3, XI li OR.— OCH3,—OR, C -l ' .— R, and G,i k wherein R is C1-C6 linear or branched alkyl (e.g., C1-C6, C1-C5, C1-C4, C 1-C3, C1-C2, CI , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl ). In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— O?,— NR3 , halo (e.g., F, Br, CI, I), trihaiide (e.g.,— CF3, CCk ---CBr3, ---(¾), --CN, SO;! !, --COOH, --COOR, --CHO, and — COR, wherein R is C1-C6 linear or branched alkyl (e.g., C 1-C6, C1-C5, C1-C4, C 1-C3, Cl- C2, CI , C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
[594] In some variations of formula (24) described in the two paragraphs above, the pendant phenyl ring of the first D2 is unsubstituted. In some variations of formula (24) described in the paragraph above, the pendant phenyl ring of the first D2 is substituted with 1-3 (e.g., 1-3, 1-2, 1, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of the first D2 is substituted, the substituents are selected independently from— -NH2,— NHR, — NR2,—OH,— O",— NHCOCH3,— NHCOR,— OCH3,—OR, CM .— , and— C6H5, wherein R is C1-C6 linear or branched alkyl (e.g., C1-C6, C1 -C5, C1-C4, C1 -C3, C1 -C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of the first D2 is substituted, the substituents are selected independently from— -NO2,— -NR^, halo (e.g., F, Br, CI, I), trihaiide (e.g.,— CF3,— CC13,— CBr3,— CI3),— CN,— S03H,— COOH, — COOR,— CHO, and— COR, wherein Ris C1-C6 linear or branched alky! (e.g., C1-C6, Cl- C5, C1-C4, C1-C3, C1-C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched a iky I)
[595] In some variations of formula (24) described in the three paragraphs above, the pendant phenyl ring of the second D2 is unsubstituted. In some variations of formula (24) described in the paragraph above, the pendant phenyl ring of the second D2 is substituted with 1-3 (e.g., 1-3, 1-2, 1, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of the second D2 is substituted, the substituents are selected independently from— H2,— NHR, — -NR2, 011. 0", M [('(){' II;. --NHCOR, --OCH3, OR, ---C2H5, R, and Crjk wherein Ris C1-C6 linear or branched alkyl (e.g., C1-C6, C1-C5, C1-C4, C1-C3, C1-C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of the second D2 is substituted, the substituents are selected independently from— NQ2,— NR3 +, halo (e.g., F, Br, CI, I), trihalide (e.g., C '.-, (Tk --€Br3, --€I3), --CN, SO;! I, --COOH, — COOR,—CHO, and— COR, wherein Ris C1-C6 linear or branched alkyl (e.g., CI-C6, Cl- C5, C1-C4, C1-C3, C1-C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl).
[596] In some of the variations of formula (24) described above, in which each D is a safranin- O moiety, as shown in formula (24a):
Figure imgf000194_0001
^ ^ , in which m, i, I2, ring
A, Rai, Rjj,! Ra2, and w are as defined in the paragraphs above, i, R2, R3, Rj, R¾, and ¾ independently are absent or independently are selected from— H?,— NHR,— R2,— OH, --()",— HCOCH3, NHCOR, --OCH3, O --C2H5, R, C;j k --N02, ---NR3 +, halo (e.g., F, Br, CI, I), trihalide (e.g.,— CF3,— CCi3,— CBr3,— CI3),— CN,— SO3H,— COOH, --COOR, --CHO, and -----COR), and R is CI-C6 linear or branched alkyl (e.g., C1-C6, C1-C5, C1-C4, C1-C3, C1-C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4- C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl), [597] One of skill in the art can readily visualize and prepare other cationic mul timers falling within formula (24) in which other cationic dye moieties are used in place of one or both of the safranin-0 moieties.
Some cationic dye multimers fall within formula (25):
Figure imgf000195_0001
(25) in which m is 2, each of Dl, a first D2, and a second D2 is a cationic dye moiety; //, /?, «, oj, and o2 independently are
A is aryl, heteroaryl, cycloalkyl, or heterocyccllyyl; for each independent instance o Rai and and Rbi(l) independently are H or CH3, or (2) Rai and ¾i independently are
Figure imgf000195_0002
O
or 3 tw0 of RaiRbi are l ; for each independent instance of Ra2 and R¾2, Ra2 and
Rb2 (1) independently are H or CH3, or (2) Ra2 and Rj,2 independently are
Figure imgf000195_0003
or or (3) two ot CRa2B*2 are 1 ; tor each independent instance ot R«i and Rdi, ti and ¾ι (1 )
O
independently are II or CH3, or (2) Rcl and di independently are "¾ or '¾ or (3) two of CRciRui are '¾^Sn^ ; and, for each independent instance of c2 and R<j2; R^ and Rd2 (1)
O
independently are H or CH3, or (2) c2 and R,j2 independently are "¾ or ' «· or (3) two of
CKc2Kd2 are
[599] In some variations of formula (25), Dl, the first D2, and the second D2 are different cationic dye moieties. In some variations of formula (25), Dl, the first D2, and the second D2 are the same cationic dye moiety. In other variations of formula (25), Dl and the first D2 are the same cationic dye moiety and the second D2 is a different cationic dye moiety. In other variations of formula (25), Dl and the second D2 are the same cationic dye moiety and the first D2 is a different cationic dye moiety. In other variations of formula (25), the first D2 and the second D2 are the same catiomc dye moiety and Dl is a different cationic dye moiety. In some variations of formula (25), each of Dl, the first D2, and the second D2 independently is selected from the group consisting of safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue.
[600] In some variations of formula (25) described in the paragraphs above, h is 1-4, 1-3, 1-2, 2-4, 2-3, 3 4, 1, 2, 3, or 4.
[601] In some variati ons of formula (25) described in the paragraphs above, I? is 1-4, 1-3, 1-2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[602] In some previous variations of formula (25) described in the paragraphs above, oj is 1-4, 1 -3, 1-2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[603] In some previous variations of formula (25) described in the paragraphs above, o2 is 1-4, 1 -3, 1-2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[604] In some variations of formula (25) described in the paragraphs above in which l} is 1, Rai and Rbi are both H. In some variations of formula (25) described in the paragraphs above in which l} is 1 , Rai is H and R¾i is O . In some variations of formula (25) described in the paragraphs above in whi ch !} is 1, Rai and J¾,i are both CH3. In some variations of formula (25) described in the paragraphs above in which // is 1, aj and R i are '¾ . In some variations of
O
formula (25) described in the paragraphs above in which h is 1 , ai and R i are · .
In variations of formula (25) described in the paragraphs above in which // is 2, the two instances of Ra and j, are indicated as Ral and Rbi and Ra2 and Ι½, respectively. In some variations of formula (25) described in the paragraphs above in which is 2, each of Rai and bi and Ra2 and t^is H. In some variations of formula (25) described in the paragraphs above in which 1] is 2, each of Rai and i and Ra2 and Rbi is CH3. In some variations of formula (25) described in the paragraphs above in which lj is 2, each of ai and Ra2 is H and each of M and Rb2 is CH3. In some variations of formula (25) described in the paragraphs above in which l} is 2, each of RaJ, Ra2, and R i is H and ¾2 is CH3. 6] In some variations of formula (25) described in the paragraphs above in which l} is 2,
Figure imgf000197_0001
each of Rai and RM i s H and , In some variations of formula (25) described in the paragraphs above in which ; is 2, each of Rai and ¾i is H and Ra2 and R^i are O
< . In some variations ot formula (25) described in the paragraphs above in which // is 2, each of a¾ and RM is CH3 and Ra2 and j,2 are "¾ . In some variations of formula (25) described in the paragraphs above in which is 2, each of Rai and R¾i is CH3 and R^ and R¾2 o
are ¾- * .
In some variations of formula (25) descri bed in the paragraphs above in which i s 2, Ral is H, is (Ί f and Ra2 and Rj>2 are "¾ . In some variations of formula (25) described in the
O
paragraphs above in which l} is 2, ai is H, Rj>i is CH3, and Ra2 and Rj,2 are . In some variations of formula (25) described in the paragraphs above in which l} i s 2, Rai and R¾i and
Ra2 and j,2 together are ^1- . In some variations of formula (25) described in the paragraphs above in which is 2, Rai and j,i are ^ ^ and j)2 are "¾ . In some variations of formula (25) described in the paragraphs above in which is 2, Rai and R1(i are ^ and
O
j,2 are "*· . In some variations of formula (25) described in the paragraphs above in which /
O O
is 2, Ral and M are '¾· ^ and Rb2 are '¾· ^\
[607] In variations of formula (25) described in the paragraphs above in which lj is 3, the three instances of Ra and Rj, are indicated as as and t^; Ra2 and R^; and A3 and &3, respectively. In some variations of formula (25) described in the paragraphs above in which lj is 3, In some variations of formula (25) described in the paragraphs above in which ; is 3, each of Rai,Rbi, ¾2, 2, a3, and a is H. In some variations of formula (25) descri bed in the paragraphs abovi in which l} is 3, each of Raj,Rbi, a2, b2, Ra3, and ^ is CH3. In some variations of formula (25) described in the paragraphs above in which lj is 3, each of Rai,Rj>i, R_ , and i»2, is H and each of Ra3 and bs is ( I f In some variations of formula (25) described in the paragraphs abov< in which is 3, each of Rai,Rt>i, ¾2, and Rb2, is CH3 and each of R¾3 and Rw is H. In some variations of formula (25) described in the paragraphs above in which is 3, Ral is H and each of R 2, 3, Rbi, Rb2, and Rbs s (Ί \ . In some variations of formula (25) described in the paragraphs above in which l} is 3, each of ai and Ra2 is H and each of Ra3, R i, R 2, and Rb3 is CI¾. In some variations of formula (25) described in the paragraphs above in which // is 3, each of Rai, Ra2, and Raj is H and each of Rbi, Rb2, and R 3 is CH3.
SOS] In some variations of formula (25) described in the paragraphs above in which // is 3, each of Rai ,Rbi, a2, and Rb2, is H and and 3 are ^2- . In some variations of formula (25) described in the paragraphs above in which is 3, each of Rai,Rbi, Ra2, and R 2, is CH3 and Ra3 and Rb3 are "^- . In some variations of formula (25) described in the paragrap above in which lj is 3, Rai is H and each of Ra2, Rbi, and Rb2 is CH3, and Ra3 and Rb3 are
Figure imgf000198_0001
, In some variations of formula (25) described in the paragraphs above in which l} is 3, each of Rai and Ra2 is H and each of Rbi and R 2 is CH3, and aj and Rb3 are
Figure imgf000198_0002
[609] In some variations of formula (25) described in the paragraphs above in which / is 3,
O
each of Rai,Rbi, a2, and Rb2, is H and R^ and Rb3 are '^- In some variations of formula (25) described in the paragraphs above in which is 3, each of Rai,Rbi, Ra2, and R 2, is CH3 and a3
O
and R 3 are '¾· ^\ In some variations of formula (25 ) described in the paragraphs above in which
O
// is 3, Rai is H and each of Ra2, Rbi, and R 2 is CH3, and R¾3 and b3 are ^\ In some vari ations of formula (25) described in the paragraphs above in which !} is 3, each of ai and a2
O
is H and each of Rbi and Rb2 is CH3, and Ra3 and Rb3 are '¾ *" .
[610] In some variations of formul a (25) described in the paragraphs above in which // is 3, Rai
V V
and Rb{ are '¾ , Ra2 and R 2 are '¾ , and each of aj and Rb3 is H. In som variations of formula (25) described in the paragraphs above in which li is 3, Ra! and bj are
Figure imgf000198_0003
, Ra2 and L,2 are '¾ , and each of Ra3 and ¾3 is CH3. In some variations of formula (25) described in the paragraphs above in which lj is 3, Rai and ϊ¾ι are ^\ a2 and b2 are Raa is H, and Rb3is CH3. In some variations of formula (25) described in the paragraphs above in which lj
Figure imgf000199_0001
is 3, Rai and R¾i are and each of R33 and
Figure imgf000199_0002
is H. In some variations of formula (25) described in the paragraphs above in which i} is 3, Ra! and ¾j are
'¾ ^ , Ra2 and j,2 are ^ , and each of aa and R 3 is CH3. In some variations of formula (25) described in the paragraphs above in which i} is 3, ai and bi are "¾· Ra? and b2 are
' W ^\ Raj s H, and Rb3is CH3.
[611] In some variations of formula (25) described in the paragraphs above in which / is 3, Rai and Rbi
Figure imgf000199_0003
and b is H. In some variations of formula (25) described in the paragraphs above in which li is 3, ai and R¾i are '¾ a2 and
O
Rb2 are ^ , and each of a3 and b3 is CH3. In some variations of formula (25) described in
r— O
the paragraphs above in which / is 3, Rai and i are '¾ a2 and ¾ are '¾· Ra3 is H, and Rb3is CH3. In some variations of formula (25) described in the paragraphs above in which i}
V 7 O
¾ X
is 3, Ra3 and bj are "¾ a2 and ^are '¾· and each of Ra3 and Rb3is H. In some variations of formula (25) described in the paragraphs above in which l is 3, Rai and Rbi are ns of formula
Figure imgf000199_0004
(25) described in the paragraphs above in which l} is 3, Rai and bi are Ra2 and Rb2 are
O
Ά '¾· *\ Ra3 is H, and Rb3 is CH3. [612] In some variations of formula (25) described in the paragraphs above in which l} is 3, Ral and ¾i are
Figure imgf000200_0001
and .-? is H. In some variations of
O
formula (25) described in the paragraphs above in which i is 3, Rai and ¾ι are ** R^ and
Rb2 are
Figure imgf000200_0002
and each of Ra3 and Rb3 is CH3. In some variations of formula (25) descri bed in
O O
the paragraphs above in which l} is 3, Rai and Rbi are ¼ A ^ <* , Ra2 and ^ are ¾ Ra3 is H, and Rb3 i s CH3. In some variations of formula (25) described in the paragraphs above in which lj
O O
is 3, Rai and Rbi are '¾· Ra2 and 2 are and each of a3 and Rb3 is H. In some variations of formula (25) described in the paragraphs above in which h i s 3, ai and R¾i are O O
"^- Ka2 and Rj,2 are and each of Ra3 and Rb3 is CH3. In some variations of formula (25)
O O
described in the paragraphs above in which // is 3, Ra} and j,i are , a2 and R*,2 are ¾ ,
Figure imgf000200_0003
[613] In some variations of formula (25) described in the paragraphs above in which is 3, RaJ and bi and Ra2 and 2 together are - and each of Ra3 and *»3 i s H. In some variations of formula (25) described in the paragraphs above in which lj is 3, ai and Rbi and a2 and R^i together are ^ " ^^i^ and each of Ra3 and i,3 is CH3. In some variations of formula (25) described in the paragraphs above in which / is 3, Rai and Rbi and a2 and Rj,2 together are
, Ra3 is H, and b is CH3. In some variations of formula (25) described in the paragraphs above in which // is 3, Ra3 and i and aa and ¾,2 together are '¾ , and a3 and *,3 are
In some variations of formula (25) described in the paragraphs above in which ; is 3, Rai and i and a2 and ¾2 together are " <· and as and ¾3 are
Figure imgf000200_0004
,
[614] In variations of formula (25) described in the paragraphs above in which ¾ is 4, the three instances of Ra and are indicated as Rai and Rbi; Ra2 and Rb2; as and R^ and 34 and R¾4, respectively. In some variations of formula (25) described in the paragraphs above in which is 4, In some variations of formula (25) described in the paragraphs above in which !i is 4, each of RaS,RM, Ra2, Rj,2, a3, ¾>3, Ra4, and Rb4 is H. In some variations of formula (25) described in the paragraphs above in which l} is 4, each of Rai,Rbi, a2, R¾2, a3, ¾»3, a4, and 4 is CH3. In some variations of formula (25) described in the paragraphs above in which is 4, each of Rai, M, 2, Rb2, 3, and R¾3 is H and each of Ra4 and 4 is (Ί ! ;. In some variations of formula (25) described in the paragraphs above in which 1} is 4, each of Raj, Rbi, a2, and j>2 is H and each of Ra3, Rj>3, RA4, and
Figure imgf000201_0001
is CH3. In some variations of formula (25) described in the paragraphs above in which ¾ is 4, each of Rai, RM, Ra2, ¾2, Ra3, and ^ is CH3 and each of ¾4 and Rb4 is H.
[615] In some variations of formula (25) described in the paragraphs above in which i is 4, each of Rai,Ra2, and Ra3 is H and each of M, R 2, and H^s is CH3. In some variations of formula (25) descri bed in the paragraphs above in which lt i s 4, Raj is H, Rbl is CH3, and each of a2, ¾2, a3; and ¾3 is CH3. In some variations of formula (25) described in the paragraphs above in which lj is 4, Rai is H, R¾i is CH3, and each of a2, Ri»2, Ra3, and 1(j is H. In some variations of formula (25) described in the paragraphs above in which i} is 4, each of Rai and R^ is H, each of M and Rb2 is CH3, and each of RA3 and j,3 is H. In some variations of formula (25) described in the paragraphs above in which h is 4, each of Rai and R^ is H, each of M and Rb2 is CH3, and each of a3 and ^? is CH .
[616] In some variations of formula (25) described in the paragraphs above in which l} is 4, Rai
Figure imgf000201_0002
and RM are H, . In some variations of formula (25) described in the paragraphs above in which l} is 4, Ra! and Rw are H,
Ra2 and 2 are H, Ra and Rb3 are CH3, and Ra4 and R¾ are . In some variations of formula (25) described in the paragraphs above in which !} is 4, Rai and R are H, R^ and Rt,2
Figure imgf000201_0003
are CH3, . In some vari ations of formula (25) described in the paragraphs above in which 1} is 4, RAI and M are CH3, RA2 and Rb2 are CH3,
Ra3 and 3 are CH3, and RA4 and R¾4 are w .
[617] In some variations of formula (25) describ the paragraphs above in which i} is 4, RAJ and Rbi are H, Ra2 and j are H, Ra3 and ¾>3 are
Figure imgf000201_0004
, and Ra4 and Rb4 are . In some variations of formula (25) described in the paragraphs above in which ¾ i s 4, Rai and Rbi are H, Ra2 and are CH3, Ra3 and j>3 are "^- and Ra4 and ~RM are . In some variations of formula (25) described in the paragraphs above in which I is 4, Rai and Riti are CH3, Ra2 and
Rs,2 are CH3, Ra3 and ¾3 are
Figure imgf000202_0001
RA4 and ¾4 are "¾ . In some variations of formula (25) described in the paragraphs above in which 1} is 4, Rai is H, ¾j is CH3, Ra2 and Rj,2 are
CH3, Ra3 and R¾,3 are ¾- and Ra4 and ¾ are
Figure imgf000202_0002
. In some variations of formula (25) described in the paragraphs above in which ; is 4, R at is H, fci is H3, Ra2 is H, b2 is CH3,
Figure imgf000202_0003
and Rb3 are .
[618] In some variations of formula (25) described in the paragraphs above in which l} is 4, Rai and j,i are H, R^ and j,2 are '^- Ra3 and R¾3 are '¾ and Ra4 and M are "¾ , In some variations of formula (25) described in the paragraphs above in which l} is 4, Rai and RM
Figure imgf000202_0004
are CH3, RA2 and ¾2 are ' - , A3 and I¾3 are In some vari ations of formula (25) described in the paragraphs above in which is 4, aj is H, M is
CH3, a2 and i»2 are S£ and ¾3 are '¾S£ and RA4 and t,4 are " V¾Si . In some variations of formula (25) described in the paragraphs above in which l} is 4, ai and ¾i are
< - ; and Rb2 are N£ Ra3 and Rb3 are S£ and Ra and Rj> are ^ .
[619] In some variations of formula 25) described in the paragraphs above in which i} is 4, RaJ and Rbi are H,
Figure imgf000202_0005
. In some variations of formula (25) described in the paragraphs above in which ; is 4, ai and M are H,
O
Ra2 and t,2 are II, Ra3 and t,3 are CH3, and Ra4 and R¾4 are '¾· . In some variations of formula (25) described in the paragraphs above in which l} is 4, ai and ¾i are H, Ra2 and Rb2
O
are CH3, aj and t,3 are C¾, and Ra4 and R¾4 are '¾· *" . In some variations of formula (25) described in the paragraphs above in which 1} is 4, Rai and Rbi are CH3, Ra2 and Rb2 are CH3,
Ra3 and (,3 are CH3, and Ra4 and R¾,4 are X- . [620] In some variations of formula (25) described in the paragraphs above in which l} is 4, Rai
O
and ¾i are H, Ra2 and Rj>2 are H, Ra3 and ¾3 are ¾ A· , and Ra4 and ¾4 are v. In some variations of formula (25) described in the paragraphs above in which h i s 4, 3i and R¾i are H,
O O
Ra2 and ί½ are CH3, Ra3 and ¾3 are "^- , and Ra4 and R^ are "^- *" . In some variations of formula (25) described in the paragraphs above in which lj is 4, Ra! and are CH3, Ra2 and
O O
Rb2 are CH3, Ra3 and R|>3 are ^\ and Ra4 and are · In some variations ot formula (25) described in the paragraphs above in which / is 4, Rai is H, RM is CH , Ra2 and j>2 are CH3, Ra3 and ¾3 are
Figure imgf000203_0001
described in the paragraphs above in which lj is 4, Rai is H, Rj,i is CH3, Ra2 is H, ¾2 is C¾, Ra3
O O
' A ¾ .
and Rj,3 are '^- 5 , and Ra4 and ¾4 are
[621] In some variations of formula (25) described in the paragraphs above in which l} is 4, Rai
0 0 O
\A A ¾A
and Rfci are H, Ra2 and j,2 are - , a3 and ¾,3 are ? and a4 and j,4 are ^ . In some variations of formula (25) described in the paragraphs above in which is 4, ai and R i are
0 0 o
CH3, Ra2 and ¾2 are A Ra3 and Rb3 are X and Ra4 and ¾4 are A f" . In some variations of formula (25) described in the paragraphs above in which h i s 4, ai is H, ¾i i s
0 0 o
CH3, Ra2 and R¾,2 are %'^A- Ra3 and Rj)3 are ¼ "^A- and Ra4 and ^ are '¾Α· In some variations
0 of formula (25) described in the paragraphs above in which / is 4, as and ^ are -A Ra2 and Rt,2 are
Figure imgf000203_0002
.
[622] In some variations of formula (25) described in the paragraphs above in which lj is 4, ai and RM are
Figure imgf000203_0003
In some variations of formula (25) described in the paragraphs above in which i} is 4, Ra! and &j are ¾
"¾ Ra2 and R¾2 are CH3, ^ and ¾3 are CH3> and R34 and ¾4 are f\ In some variations of formula (25) described in the paragraphs above in which h is 4, Ral and Rbi are
Figure imgf000204_0001
and Rb2 are H, Ra3 and Rb are CH3, and Ra4 and Rb4 are
Figure imgf000204_0002
[623] In some variations of formula (25) described in the paragraphs above in which l} is 4, R8l
Figure imgf000204_0003
and Rbi are '¾· <*\ In some variations of formula (25) described in the paragraphs above in which // is 4, Ra} and bi
O
\X X X
are " \ Ra2 and Rb2 are '¾ ~ , ^ and Rb3 are CH3, and Ra4 and Rb4 are ' L . In some variations of formula (25) described in the paragraphs above in which ; i s 4, ai and Rbi are
Figure imgf000204_0004
. In some variations of formula (25) described in the paragraphs above in which li is 4, Ral and RM are
Figure imgf000204_0005
, Ra2 and Rb2 are , Ra3 and Rb are H, and Ra4 and Rb4 are .
[624] In some variations of formula (25) described in the paragraphs above in which h is 4, Rai and Rbi are X Ra2 and j>2 are
Figure imgf000204_0006
[625] In some variati ons of formula (25) described in the paragraphs above in which h is 4, Rai
Figure imgf000204_0007
and Rbi are '¾ Ra2 and Rb2 are In some vari ations of formula (25) described in the paragraphs above in which h is 4, Rai and Rbi
O O
are vv Ra2 and R,l2 are ¾ js ¾ and RJ>3 are CH3, and Ra4 and RM are «¾X In some variations of formula (25) described in the paragraphs above in which / is 4, Ra! and bj are
O O
'vv , Ra2 and Rb2 are v '¾· f\ Ra3 and Rb3 are CH , and Ra4 and Rb4 are U '¾· f\ In some variations of formula (25) described in the paragraphs above in which i s 4, ai and R i are
O O
-¾ f- ^ Ra2 an£j iib2 are -\ ¾a3 anc Rb3 are anc| ]¾a4 anc| ¾b4 are -\ .
[626] In some variations of formula (25) described in the paragraphs above in which h is 4, Rai and bi are
Figure imgf000205_0001
[627] In some variations of formula (25) described in the paragraphs above in which / is 4, Rai and Rj,i are
Figure imgf000205_0002
In some variations of formula (25) described in the paragraphs above in which h is 4, aj and j are
0 0 o
f\ Ra2 and Rj,2 are ' «· 33 and R¾s are CH3, and Ra4 and Rb4 are 5 , In some variations of formula (25) described in the paragraphs above in which i} is 4, Ra! and R i are
Figure imgf000205_0003
In some variations of formula (25) described in the paragraphs above in which lj is 4, Rai and R¾i are 0 0 o
% A
'¾· Ra2 and Rb2 are a3 and b3 are H, and Ra4 and Rb4 are ^ .
[628] In some variations of formula (25) described in the paragraphs above in which l} is 4, Rai and w are
Figure imgf000205_0004
.
[629] In some variations of formula (25) described in the paragraphs above in which lj is 4, Ral and Rbi are H, R^ and b2 are H, and ^ and b3 and Ra4 and Rb together are "^- . In some variations of formula (25) described in the paragraphs above in which / is 4, Ra} and i are H, Ra2 and Rb2 are CH3, and Ra3 and Rb3 and Ra4 and R 4 together are ¾ . In some variations of formula (25) described in the paragraphs above in which l} is 4, ai and Ra2 are H, bi and Rb2 are CH3, and Ra3 and Rb3 and Ra4 and Rb4 together are "^- V
[630] In some variations of formula (25) described in the paragraphs above in which i is 4, Rai and Rbi are H, R^ and b2 are and Ra3 and Rb3 and Ra4 and Rb4 together are - . In some variations of formula (25) described in the paragraphs above in which !i is 4, Rai and Rbi
Figure imgf000206_0001
, Ra2 and Rb2 are (Ί f and Ra3 and 3 and Ra4 and R¾4 together are ' ·- ¾ . In some variations of formula (25) described in the paragraphs above in which i} is 4, Ra! is H, Rbi is a2 and ¾2 are '¾ ^\ and Ra3 and 3 and Ra4 and ¾4 together are
[631] In some variati ons of formula (25) described in the paragraphs above in which / is 4, Rai
O
and Rj,i are H, ^ and R 2 are and Ra3 and b3 and RA4 and RB4 together are . In some variations of formula (25) described in the paragraphs above in which l} is 4, and ¾ι O
are '¾· Ra2 and Rb2 are CH3, and Ra3 and R 3 and Ra4 and RB together are ¾ , In some variations of formula (25) described in the paragraphs above in which l} is 4, Ra! is H, Rbi is
O
CH3, Ra2 and R 2 are % '¾ A· and R^ and RB3 and RA4 and Rb4 together are 1^ Y V
[632] In some variations of formula (25) described in the paragraphs above in which l} is 4, Rai and bi are
Figure imgf000206_0002
. In some variations of formula (25) described in the paragraphs above in which lj is 4, Rai and
Figure imgf000206_0003
and Ra3 and Rb3 and Ra4 and Rb4 together are An some variations of formula (25) described in the paragraphs above in which !} is 4, Ral and RBL are
Figure imgf000206_0004
and a and b and Ra4 and Rb4 together are Y
[633] In some variations of formula (25) described in the paragraphs above in which // is 4, Rai and Rbi a
Figure imgf000206_0005
and RB2 are " <¾rS£ and and Rb3 and RA4 and Rb4 together are
[634] In some variations of formula (25) described in the paragraphs above in which lj is 4, RAJ and bi and Ra2 and R 2 together are - \ and R^ and RM and a4 and Rb4 together are [635] In some variations of formula (25) described in the paragraphs above in which l2 h 1 , Rai and ¾ί are both H. In some variations of formula (25) described in the paragraphs above in which l2 is 1 , Rai is H and R¾i is CH3. In some variations of formula (25) described in the paragraphs above in which ? is 1, Rai and Rbi are both CH3. In some variations of formula (25) described in the paragraphs above in which 12 is 1, Rai and i are "¾ . In some variations of
O
formula (25) described in the paragraphs above in which l2 is I, Rai and &j are ^\
[636] In variations of formula (25) described in the paragraphs above in which l2 is 2, the two instances of Ra and Rj, are indicated as ai and i and Ra2 and R 2, respectively. In some variations of formula (25) described in the paragraphs above in which l2 is 2, each of Rai and Rbi and Ra2 and 2 is H. In some variations of formula (25) described in the paragraphs above in which l2 is 2, each of Rai and Rbi and ^ and 2 s CH3. In some variations of formula (25) described in the paragraphs above in which l2 is 2, each of Rai and Ra2 is H and each of RM and Rb2 is CH3. In some variations of formula (25) described in the paragraphs above in which l2 is 2, each of Rai, Ra2, and Rbi is H and ¾2 is CH3.
[637] In some variati ons of formul a (25) described in the paragraphs above in which l2 is 2, each of Ra{ and Rbi is H and Ra2 and ¾2 are '¾ . In some variations of formula (25) described in the paragraphs above in which l2 is 2, each of Rai and Rbi is H and ^ and j,2 are O
'¾· . In some variations of formula (25) described in the paragraphs above in which l2 is 2, each of ai and M is CH3 and Ra2 and b2 are '¾ . In some variations of formula (25) described in the paragraphs above in which l2 is 2, each of ai and R1(i is CH3 and Ra2 and R¾2 O
are
In some variations of formula (25) described in the paragraphs above in which l2 i s 2, Ra3 is H, bi is CH3, and Ra2 and 2 are '¾¾ . In some variations of formula (25) described in the
O
paragraphs above in which l2 is 2, Rai is H, i is CH3, and Ra2 and ¾2 are ' <- . In some variations of formula (25) described in the paragraphs above in which l2 is 2, Ra! and ¾i and Ra2 and ¾2 together are ' ¾ . In some variations of formula (25) described in the paragraphs above in which l2 is 2, Rai and ¾i are '^- ** ¾ and ¾2 are '^- . In some variations of formula 25) described in the paragraphs above in which I? is 2, Ral and bi are ^ Ra2 and
Rb2 are
Figure imgf000208_0001
in some variations of formula (25) described in the paragraphs above in which l2
O O
is 2, Ral and bi are '¾ Ra2 and b2 are ^\
[638] In variations of formula (25) described in the paragraphs above in which l2 is 3, the three instances of Ra and Rb are indicated as ai and bi; Ra2 and b2; and Ra3 and ¾. respectively. In some variations of formula (25) described in the paragraphs above in which l2 is 3, In some variations of formula (25) described in the paragraphs above in which h is 3, each of Rai,Rbi, Ra2, R¾2, a3, and ¾3 is H. In some variations of formula (25) described in the paragraphs above in which l2 is 3, each of Rai,Rbi, Ra2, Rb2, Ras, and
Figure imgf000208_0002
is CH3. In some variations of formula (25) described in the paragraphs above in which l2 is 3, each of Rai,Rbj, Ra2, and Rb2, is H and each of Ra3 and R^ is CH3. In some variations of formula (25) described in the paragraphs above in which l2 is 3, each of Rai,Rbi, a2, and ¾2, is CH3 and each of Ra3 and bs is H. In some variations of formula (25) described in the paragraphs above in which l2 is 3, Rai is H and each of Ra2, A3. Rbi, Rb2, and Rb3 is CH3. In some variations of formula (25) described in the paragraphs above in which l2 is 3, each of Rai and Ra2 is H and each of Raj, Rbi, ¾2, and ¾3 is CH3. In some variations of formula (25) described in the paragraphs above in which l2 is 3, each of Rai, Ra2, and 33 is H and each of Rbi, RM, and bs s (Ί \ .
[639] In some variations of formula (25) described in the paragraphs above in which l2 is 3, each of Rai,Rbi, a2, and Rb2, is H and
Figure imgf000208_0003
. In some variations of formula (25) described in the paragraphs above in which l2 is 3, each of Rai,Rbi, RA2, and Rb2, is CH3 and A3 and Rb3 are " . In some variations of formula (25) described in the paragraphs above in which l2 is 3, Rai is H and each of Ra2, Rbi, and Rb2 is CH3, and Ra3 and Rb3 are "^- . in some variations of formula (25) described in the paragraphs above in which l2 is 3, each of Rai and Ra2 is H and each of Rbi and R1(2 is CH3, and 33 and s are
Figure imgf000208_0004
[640] In some variations of formula (25) described in the paragraphs above in which l2 is 3,
O
each of Rai,Rw, Ra2, and ¾>2, is H and Ra3 and l¾3 are ^\ In some variations of formula (25) described in the paragraphs above in which l2 is 3, each of Rai,¾i, Ra2, and ¾2, is CH3 and Ra3
O
and Rj,3 are '^- . In some variations of formula (25 ) described in the paragraphs above in which
O
h is 3, Rai is H and each of Ra2, Rbj, and i,2 is CH3, and R^ and Rj,3 are ^ \ In some variations of formula (25) described in the paragraphs above in which l2 is 3, each of Rai and Ra2
O
is H and each of Rbi and ¾2 is CH3, and Raj and R¾3 are
[641] In some variations of formu described in the paragraphs above in which l2 is 3, ai and RM a
Figure imgf000209_0001
, and each of Raj and ¾3 is H. In some variations ot formula (25) described in the paragraphs above in which l2 is 3, Ra! and ¾i are '¾ , Ra2 and
Rj,2 re '¾ and each of Ra3 and ^s i CH3. In some variations of formula (25) described in the paragraphs above in which l2 is 3, RaJ and Rbi are '¾ *" , Ra2 and Rb2 are '¾ ^ is H, and i>3 is CH3. In some variations of formula (25) described in the paragraphs above in which l2
Figure imgf000209_0002
, Ra2 and j,2 are "¾ , and each of Ra3 and R 3 is H. In some
ribed in the paragraphs above in which l2 is 3, Rai and Rbi are
Figure imgf000209_0003
ancf each of Ra3 an(j Rb3 is CH3. In some variations of formula
(25) described in the paragraphs above in which l2 is 3, Rai and Rbi are '¾ Ra2 and Rb2 are
" \¾¾ , Raj is H, and Rh3 is CH3.
[642] In some variations of formula (25) described in the paragraphs above in which l2 is 3, ai
*r O
and R i are , Ra2 and ¾2 are and each of R^ and ¾3 is H. In some variations of formula (25) described in the paragraphs above in which l2 is 3, Rai and Rbi are '¾· Ra2 and O
¾2 are ' *· and each of Ra3 and j>3 is CH3. In some variations of formula (25) described in
— ^
the paragraphs above in which l2 is 3, ai and M are "¾ , A2 and R¾2 are A3 is H, and bjis CH3. In some variations of formula (25) described in the paragraphs above in which l2
O
is 3, Rai and R¾i are "x ^ , Ra2 and Rj,2are '¾· and each of A3 and ^is H. In some variations of formula (25) described in the paragraphs above in which is 3, ai and M are j O
'¾ Ra2 and J¾,2are '¾ f\ and each of Raj and Rwis CH3. In some variations of formula
(25) described in the paragraphs above in which l2 is 3, Rai and j,i are '¾ , Ra2 and ¾2 are O
-\ Ra3 is H, and ¾ is CH3.
[643] In some variations of formula (25) described in the paragraphs above in which l2 is 3, Rai
O O
and Rj,i are Ra2 and Rb2are and each of as and b3is H. In some variations of
O
formula (25) described in the paragraphs above in which h is 3, ai and ¾i are · ^*, Ra2 and
O
Rj)2 are f\ and each of Raj and ¾3 is CH3. In some variations of formula (25) described in
O O
the paragraphs above in which l2 is 3, Rai and Ι¾ί are * , Ra2 and ¾ are · A is H, and i,3is CH3. In some variations of formula (25) described in the paragraphs above in which l2 is 3, ai and R i are
Figure imgf000210_0001
is H. In some variations of formula (25) described in the paragraphs above in which l2 is 3, aj and &j are O O
' L <* Ra2 and j)2 are '¾· and each of Raj and Rb3 is CH3. In some variations of formula (25)
o o described in the paragraphs above in which 12 is 3, Rai and Rbi are "*· Ra2 and R2 are · Ra3 is H, and i»3 is CH3. [644] In some variations of formula (25) described in the paragraphs above in which l2 is 3, Rai and ¾i and Ra2 and j,2 together are " and each of aa and Rj>3 is H. In some variations of formula (25) described in the paragraphs above in which l2 is 3, RaJ and RbJ and Ra2 and together are ' x , and each of Ra3 and ¾3 is CH3. In some variations of formula (25) described in the paragraphs above in which l2 is 3, Rai and bi and Ra2 and Rb2 together are )■ (
' L , Ra3 is H, and b3 is CH3. In some variations of formula (25) described in the paragraphs above in which l2 is 3, Rai and R|>i and Ra2 and R¾2 together are 'x and Ra3 and ¾3 are
In some variations of formula (25) described in the paragraphs above in which l2 is 3, RaX
O
and Rbi and Ra2 and Rb2 together are ""*· v a anndd R„a3¾ anηάd b3 are
[645] In vari ations of formula (25) described in the paragraphs above in which l2 is 4, the three instances of Ra and b are indicated as Rai and Rbi; Ra2 and Rb2; R^ and b3; and a4 and ¾4, respectively. In some variations of formula (25) described in the paragraphs above in which l2 is 4, In some variations of formula (25) described in the paragraphs above in which l2 is 4, each of Rai,R¾i, Ra2, Rb2, R«3, ¾3. Ra4, and R is H. In some variations of formula (25) described in the paragraphs above in which l2 is 4, each of Rai,Rt>i, ¾2, 2, a3, ¾3, a , and ¾4 is CH3. In some variations of formula (25) described in the paragraphs above in which l2 is 4, each of Rai, Ra2, Ri>2, a3, and Rb3 is H and each of Ra4 and ^ is CH3. In some variations of formula (25) described in the paragraphs above in which l2 is 4, each of Rai, R¾i, Ra2, and Rj,2 is H and each of Ra3, Rj>3. Ra4, and Rt,4 is CH3. In some variations of formula (25) described in the paragraphs above in which l2 is 4, each of Rai, Rj,i, Ra2, Rb2, a3, and ^ is CH3 and each of Ra4 and Rb4 is H.
[646] In some variations of formula (25) described in the paragraphs above in which l2 is 4, each of Ra{,Ra2, and Ra3 is I I and each of R¾i, R(,2, and j,3 is CH3. In some variations of formula (25) described in the paragraphs above in which l2 is 4, Rai is H, *i i s CH3, and each of ¾2, ¾2, a3, and Rb3 is CH3. In some variations of formula (25) described in the paragraphs above in which l2 is 4, Rai is H, R¾i is CH3, and each of R^, Rb2, a3, and Rb3 is H. In some variations of formula (25) described in the paragraphs above in which is 4, each of Rai and Ra2 i s H, each of bi and Rb2 is CH3, and each of Ra3 and Rb3 is H. In some variations of formula (25) described in the paragraphs above in which l2 is 4, each of Rai and Ra2 is H, each of R i and Rb2 is (Ί f and each of Ra3 and ¾3 is CH3. [647] In some variations of formula (25) described in the paragraphs above in which l2 is 4, Rai
Figure imgf000212_0001
and ¾ι are H, are . In some variations of formula (25) described in the paragraphs above in which l2 is 4, Ra! and R&j are H,
Ra2 and R^ are H, RA3 and Rb3 are CH3, and Ra4 and R¾4 are '¾ . In some variations of formula (25) described in the paragraphs above in which /? is 4, Rai and ¾ι are H, and ¾2 are C¾, ¾ and ¾3 are CH3, and RA4 and ¾4 are '¾ ^ , In some variations of formula (25) described in the paragraphs above in which h is 4, Rai and RM are CH3, Ra2 and j,2 are CH3,
Ra3 and j,3 are CH3, and Ra4 and R¾4 are " ^ .
[648] In some variations of formula (25) described in the paragraphs above in which l2 is 4, RaJ
Figure imgf000212_0002
and jji are H, Ra2 and j>2 are H, Ra3 and ¾3 are "^- and Ra4 and Rt> are . In some variations of formula (25) described in the paragraphs above in which l2 is 4, Rai and RM are H,
Ra2 and R¾2 are CH3, Ra3 and Ri»3 are
Figure imgf000212_0003
, In some variations of formula (25) described in the paragraphs above in which l2 is 4, Ra! and R&j are CH3, Ra2 and
Rb2 are CH3, Ra3 and Rb3 are "^- , and Ra4 and Rj,4 are "¾ . In some variations of formula (25) described in the paragraphs above in which l2 is 4, Ral is H, R¾i is CH3, Ra2 and Rj,2 are
CH , Ra3 and ¾3 are L and Ra4 and ¾4 are '¾ . In some variations of formula (25) described in is H, Rb2 is CH3, Ra3
Figure imgf000212_0004
and Rj,3 are and Ra4 a d R¾4 are .
[649] In some variations of formula (25) described in the paragraphs above in which l2 is 4, RaJ and Rbi are H, Ra2 and Rj>2 are
Figure imgf000212_0005
and Ra4 and Rj,4 are In some variations of formula (25) described in the paragraphs above in which l2 is 4, Ral and Rbl are CH3, R^ and R¾2 are "*· Ra3 and ¾3 are "¾ and Ra4 and RM are '¾ ^ . In some variations of formula (25) described in the paragraphs above in which l2 is 4, Ra! is H, Rbi is and ¾2 are "¾ ^\ Ra3 and b3 are "^- and Ra4 and Rt>4 are . In some variations of formula (25) described in the paragraphs above in which l2 is 4, ai and R i are
Figure imgf000213_0001
[650] In some variations of formula (25) described in the paragraphs above in which l2 is 4, Rai
9
and RM are H, Ra2 and ¾2 are H, Ra3 and ¾3 are II, and RA4 and ¾4 are '*> ^ . In some variations of formula (25) described in the paragraphs above in which l2 is 4, Ral and RM are H,
O
Ra2 and ^ are H, Ra3 and (,3 are CH3, and A4 and &4 are . In some variations of formula (25) described in the paragraphs above in which l2 is 4, ai and Rbi are H, ^ and j,2
O
are CH3, A3 and Rb3 are CH3, and A4 and ¾4 are ^\ In some variations of formula (25) described in the paragraphs above in which /? is 4, Rai and ¾i are CH3, Ra2 and R¾2 are CH3,
O
Ra3 and j,3 are CH3, and Ra4 and M are "^- .
[651] In some variations of formula (25) described in the paragraphs above in which l2 is 4, RaJ
O
and Rbi are H, R^ and l¾>2 are H, Ra3 and Rw are · ^\ and Ra4 and R^ are v. In some variations of formula (25) described in the paragraphs above in which /? is 4, ai and ¾i are H,
2 and Rb2 are CH3, Ra3 and s are
Figure imgf000213_0002
In some variations of formula (25) described in the paragraphs above in which l is 4, ai and bi are CH3, Ra2 and
O o
are CH3, RA3 and R¾3 are and A4 and M are · , In some variations of formula
(25) described in the paragraphs above in which l2 is 4, Rai is H, ¾i is CH3, Ra2 and j,2 are
A A CH3, Ra3 and ¾>3 are and Ra4 and 4 are In some variations of formula (25) described in the paragraphs above in which h is 4, Rai is H, R¾i is CH3, R^ is H, ¾2 is CH3, A3 and b3 are
Figure imgf000213_0003
[652] In some variations of formula (25) described in the paragraphs above in which l2 is 4, Rai and Ri>i are H, Ra2 and Rj>2 are
Figure imgf000214_0001
some variations of formula (25) described in the paragraphs above in which l2 is 4, Rai and R¾i are
0 0 o
^ ^ 5 ^-
CH3, Ra2 and R¾,2 are Ra3 and j,3 are ^*, and Ra4 and Rj>4 are "^- ^ . In some variations of formula (25) described in the paragraphs above in which l2 is 4, Ra! is H, Rh{ is
CH3, Ra2 and Rj,2 are
Figure imgf000214_0002
In some variations
O
of formula (25) described in the paragraphs above in which /? is 4, ai and ¾i are ¾ ·Α· ^ Ra2 and Ri»2 are
Figure imgf000214_0003
[653] In some variations of formula (25) described in the paragraphs above in which /? is 4, Rai and Rj,t are '¾ , Ra2 and i,2 are H, Ra3 and R¾ are H, and Ra4 and R¾4 are '¾· . In some variations of formula (25) described in the paragraphs above in which l2 is 4, Rai and R¾i are
O
and Rb2 are CH3, Ra3 and Rb3 are CH3. and Ra4 and M are '¾A *" . In some variations of formula (25) described in the paragraphs above in which l2 is 4, Rai and Ι¾ί are '¾ ^* , Ra2
O
and i,2 are H, 33 and j,3 are CH3, and Ra4 and RM are ¾ 5 ,
[654] In some variations of formula (25) described in the paragraphs above in which l2 is 4, Rai
O
and Rbi are '¾S£ , Ra2 and Rj,2 are ' ¾¾ , Ra and R¾ are H, and Ra4 and R¾4 are % . In some variations of formula (25) described in the paragraphs above in which /? is 4, Rai and Rbi
Figure imgf000214_0004
are - . In some variations of formula (25) described in the paragraphs above in which l2 s 4, Rai and R i are
< - 5 RA2 ancj RB2 ARE 'T ^ - 3 R R„A3! a annd(j ] R¾..3! a ArReE Γ CΉH-3, a anndd R RLA4< a anndd RM< a arree " '¾¾·· ^ ^ . In some variations of formula (25) described in the paragraphs above in which l2 is 4, ai and Rbi are
Figure imgf000215_0001
[655] In some variations of formula (25) described in the paragraphs above in which h is 4, RAL Vv
and Rbi are ? Ra2 and Rb2 are ? Ra3 and Rb3 are "¾ ^\ and RA4 and Rb4 are
[656] in some variations of formula (25) described in the paragraphs above in which i2 is 4, Rai and Rbi are
Figure imgf000215_0002
In some variations of formula (25) described in the paragraphs above in which l2 is 4, Rai and ¾ι
■r— 7 O O
are '¾ , Ra2 and Rb2 are "¾- ?'\ R^ and ¾3 are C¾, and Ra4 and Rb4 are '¾· f\ In some variations of formula (25) described in the ara ra hs above in which J2 is 4, Ra! and Ri.i are
Figure imgf000215_0003
Ra3 and Rb3 are CH3, and Ra4 and Rb4 are . In some variations of formula (25) described in the paragraphs above in which l2 is 4, Rai and bi are
Figure imgf000215_0004
[657] In some variations of formula (25) described in the paragraphs above in which i2 is 4, Rai and j>] are
Figure imgf000215_0005
[658] In some variations of formula (25) described in the paragraphs above in which /_? is 4, RAL and Rbi are
Figure imgf000215_0006
In some variations of formula (25) described in the paragraphs above in which is 4, aj and RM are
Figure imgf000215_0007
In some variations of formula (25) described in the paragraphs above in which /? is 4, ai and bi are
Figure imgf000215_0008
variations of formula (25) described in the paragraphs above in which l2 is 4, ai and R i are 0 0 o
· , a2 and Rb2 are ·· f\ Ra3 and Rb3 are H, and Ra and Rb are '¾· ?~ .
[659] In some variations of formula (25) described in the paragraphs above in which h is 4, Ral and bi are
Figure imgf000216_0001
.
[660] In some variations of formula (25) described in the paragraphs above in which l is 4, Rai and R i are H, ^ and R 2 are H, and and Rb3 and Ra4 and R together are . In some variations of formula (25) described in the paragraphs above in which l2 is 4, Rai and Rbi are H, R^ and Rb2 are CH3, and Ra3 and Rb3 and Ra4 and Rb together are ^ ^i n some variations of formula (25) described in the paragraphs above in which l2 is 4, Ral and Ra2 are H, j,i and Rb2 are CH3, and Ra3 and Rb3 and Ra4 and Rb4 together are .
[661] In some variations of formula (25) described in the paragraphs above in which l2 is 4, Rai and j,i are H, R^ and R 2 are '¾ , and Ra3 and R 3 and Ra4 and R 4 together are , In some variations of formula (25) described in the paragraphs above in which l2 is 4, ai and Rbi
Figure imgf000216_0002
Ra2 and Rb2 are CH3, and Ra3 and Rb3 and Ra4 and R|,4 together are '¾ Ss^ ]n some variations of formula (25) described in the paragraphs above in which l2 is 4, Ral is H, s is
CH3, Ra2 and R^ are " vv and Ra3 and R 3 and Ra4 and Rb4 together are
[662] In some variations of formula (25) described in the paragraphs above in which /? is 4, Rai
O
and Rbi are H, R^ and Rb2 are "¾ and Ra3 and Rb3 and Ra4 and Rb together are ^ r . In some variations of formula (25) described in the paragraphs above in which l2 is 4, Ral and Rbi O
are Ra2 and Rb2 are CH3, and Ra3 and R 3 and Ra4 and Rb4 together are ' *· . In some variations of formula (25) described in the paragraphs above in which /? is 4, aj is H, i is
O
CH3, Ra2 and ¾2 are and Ra3 and R 3 and Ra and Rb together are x . [663] In some variations of formula (25) described in the paragraphs above in which l2 is 4, Rai O O
and Rj>i are a2 and Rb2 are and ^ and R ? and Ra4 and b4 together are ¾ x . In some variations of formula (25) described in the paragraphs above in whi ch /? is 4, Rai and
O
Rbi are and Rb2 are "¾ ^\ and Ra3 and 3 and Ra4 and R 4 together are '^- 1. In some variations of formula (25) described in the paragraphs above in which l2 is 4, Rat and RbJ O O
are v '^A- Ra2 and Rb2 are ¾ A· / , and a3 and b3 and Ra4 and j)4 together are ¾-^ Y ¾ .
[664] In some variations of formula (25) described in the paragraphs above in which l2 is 4, Rai and j>i are ^*-, Ra2 and Rb2 are '¾ and a3 and Rb3 and a4 and R¾4 together are
[665] In some variations of formula (25) described in the paragraphs above in which l2 is 4, Rai and jji and Ra2 and Rb2 together are ^ ancf j¾a3 an(j ¾b3 an(j ¾a4 an(f Rm together are
[666] In some variations of formula (25) described in the paragraphs above in which o} is 1, Rai and Rb3 are both H. In some variations of formula (25) described in the paragraphs above in which oi is 1, Rai is H and Rbi is CH3. In some variations of formula (25) described in the paragraphs above in which o} is I, aj and bj are both CH3. In some variations of formula (25) described in the paragraphs above in which oi is 1, Rai and Rbi are ^ . In some variations of
O
¾A
formula (25) described in the paragraphs above in which oj is I, aj and bi are 5"\
[667] In variations of formula (25) described in the paragraphs above in which o} is 2, the two instances of Ra and Rb are indicated as Rai and i and Ra2 and R 2, respectively. In some variations of formula (25) described in the paragraphs above in which o} is 2, each of Rai and R i and Ra2 and R 2 is H. In some variations of formula (25) described in the paragraphs above in which Oj is 2, each of ai and Rbi and Ra2 and Rb2 is CH3. In some variations of formula (25) described in the paragraphs above in which o} is 2, each of Rai and Ra2 is H and each of j and Rb2 is CH3. In some variations of formula (25) described in the paragraphs above in which oi is 2, each of Ral, Ra2, and M is H and Rb2 is CH3.
[668] In some variations of formula (25) described in the paragraphs above in which o is 2,
Figure imgf000218_0001
each of Rai and RM is H and , In some variations of formula (25) described in the paragraphs above in which o} is 2, each of Rai and J,J is H and Ra2 and Rw an O
· . In some variations of formula (25) described in the paragraphs above in which oj is 2, each of as and R¾i is CH3 and Ra2 and j,2 are "¾ . In some variations of formula (25) described in the paragraphs above in which oi is 2, each of ai and Rj,i is CH3 and Ra2 and j,2
Figure imgf000218_0002
In some variations of formula (25) described in the paragraphs above in which o is 2, Rai is H, is (Ί f and Ra2 and Rj>2 are '¾ . In some variations of formula (25) described in the paragraphs above in which o1 is 2, Ral is H,
Figure imgf000218_0003
In some variations of formula (25) described in the paragraphs above in which os is 2, Rai and j,i and
Ra2 and Rj>2 together are . In some variations of formula (25) described in the paragraphs above in which oi is 2, aj and R¾i are '¾ .Ά2 and R¾2 are '¾ , In some variations of formula (25) described in the paragraphs above in which o} is 2, Rai and Rj,i are
Figure imgf000218_0004
Ra2 and j,2 are
Figure imgf000218_0005
. In some variations of formula (25) described in the paragraphs above in which
A A
is 2, ai and ¾i are ^ ^ and j,2 are .
[669] In variations of formula (25) described in the paragraphs above in which o} is 3, the three instances of Ra and Rb are indicated as as and t^; Ra2 and R¾2; and a3 and Rj,3, respectively. In some variations of formula (25) described in the paragraphs above in which oj is 3, In some variations of formula (25) described in the paragraphs above in which o} is 3, each of Rai,Rt>i, Ra2, R¾2, a3, and R¾3 is H. In some variations of formula (25) described in the paragraphs above in which oi is 3, each of Rai,Rbi, -R_ , ¾2, A3, and Rw is CH3. In some variations of formula (25) described in the paragraphs above in which Oj is 3, each of Rai,Rw, Ra2, and Rj,?, is H and each of Ra3 and s is CH3. In some variations of formula (25) described in the paragraphs above in which o} is 3, each of Rai,Rbi, Ra2, and Rb2, is (Ί and each of Ra3 and RM is H. In some variations of formula (25) described in the paragraphs above in which oj is 3, Rai is H and each of Ra2, Ra3, ¾i, ¾2, and Rb3 is CH3. In some variations of formula (25) described in the paragraphs above in which o/ is 3, each of Ra} and Ra2 is H and each of Ra3, Rbi, R^, and R¾3 is CH3. In some variations of formula (25) described in the paragraphs above in which o} is 3, each of ai, Ra2, and Ra3 is H and each of bi, 2, and Rb3 is CH3.
[670] In some variations of formula (25) described in the paragraphs above in which o} is 3, each of Rai,Rbi, RA2, and Rb2, is H and as and Rb3 are " ^ ^ . In some variations of formula (25) described in the paragraphs above in which Oj is 3, each of Rai,Rw, Ra2, and J¾,2, is CH3 and Ra3 and R 3 are "^- ^ . In some variations of formula (25) described in the paragraphs above in which oj is 3, ai is H and each of R^, Rbi, and Rb2 is CH3, and Ra3 and 3 are '¾ . In some variations of formula (25) described in the paragraphs above in which <¾ is 3, each of Rai and
Ra2 is H and each of bi and Rb2 is CH3, and Ra3 and Rb3 are "¾
[671 ] In some variations of formula (25) described in the paragraphs above in which o} is 3,
O
each of at, bi, Ra2, and Rb2, is H and ^ and R*,3 are ^ . In some variations of formula (25) described in the paragraphs above in which oi is 3, each of Rai, bi, ¾2, and I¾>2, is CH3 and Ra3
Figure imgf000219_0001
and Rb3 are - . In some va at ons o ormu a 25 escr e n paragraphs above in which oi is 3, Rai is H and each of Ra2, Rbi, and Rb2 is CH3, and and Rh3 are
Figure imgf000219_0002
variations of formula (25) described in the paragraphs above in which oj is 3, each of Rai and
O
Ra2 is H and each of bi and b2 is CH3, and Ra3 and Rb3 are '¾· .
[672] In some variations of formula (25) described in the paragraphs above in which o} is 3,
Rai and RM are "^- Ra2 and Rb2 are , and each of R^ and R1( is H, In some variations of formula (25) described in the paragraphs above in which o} is 3, Rai and M are "^- Ra2 and ^ are '¾ , and each of Ra3 and Rb3 is CH3. In some variations of formula (25) described in the paragraphs above in which o} is 3, RAJ and RM are
Figure imgf000220_0001
Ra2 and R|i>2 are "¾· , Ra3 is H, and s of formula (25) described in the paragraphs above in which
Figure imgf000220_0002
Ra2 and ^ are "^- , and each of Ra3 and Rba is H. In some variations of formula (25) described in the paragraphs above in which o} is 3, Rai and Rm are "^- , Ra2 and j>2 are '^- , and each of and Rb3 is CH3. In some variations of formula (25) described in the paragraphs above in which oi i s 3, Rai and M are "¾- and Rj,2 are
Figure imgf000220_0003
In some variations of formula (25) described in the paragraphs above in which oj is 3,
O
id Rhi are "x , RRaa22 aanndd RR¾¾22 aarree L ^\ aanndd eeaacch of R j and ¾3 is H. In some variations of formula (25) described in the paragraphs above in which oi is 3, Rai and ¾ι are
Figure imgf000220_0004
RA2
O
and Rb2 are ^ *" , and each of Ra3 and 1½ is CH3. In some variations of formula (25) described — O
in the paragraphs above in which oj is 3, Rai and are "¾ , RA2 and ¾2 are f\ Ra3 is H, and Rb3 i s CH3. In some variations of formula (25) described in the paragraphs above in which oi
O
is 3, Rai and ¾i are "¾ , RA2 and R^ are and each of as and R^ is H. In some variations of formula (25) described in the paragraphs above in which oj is 3, RAI and M are
O
and RK2 are ^ and each of Ra3 and RK3 is C¾. In some variations of formula
(25) described in the paragraphs above in which Oj is 3, Rai and RM are '¾ , ^ and Ri)2 are
O
Figure imgf000220_0005
[674] In some variations of formula (25) described in the paragraphs above in which oi is 3,
Riii and ¾i are
Figure imgf000221_0001
and each of Ra3 and Rb3 is H. In some variations of
O
formula (25) described in the paragraphs above in which o} is 3, Rai and Rbi are '¾· , a2 and
Rb2 are
Figure imgf000221_0002
and each of RA3 and Rb3 is CH3. In some variations of formula (25) descri bed in the paragraphs above in which oj is 3, Ral and M are
Figure imgf000221_0003
and Rb3 i s CH3. In some variations of formula (25) described in the paragraphs above in which oj
O O
is 3, Rai and R¾i are '¾· Ra2 and Rb2 are and each of A3 and Rb3 is H. In some variations of formula (25) described in the paragraphs above in which oj is 3, Rai and M are
Figure imgf000221_0004
A A
described in the paragraphs above in which oi is 3, ai and i are , Ra2 and Rb2 are
Figure imgf000221_0005
[675] In some variations of formula (25) described in the paragraphs above in which oj is 3,
Rai and Rbi and Ra2 and ¾2 together are L and each of Ra3 and R^ i s H. In some variations of formula (25) described in the paragraphs above in which o} is 3, Rai and bi and
R¾2 and Rb2 together are "^- and each of Ra3 and (,3 is CH3. In some variations of formula (25) described in the paragraphs above in which oi i s 3, Rai and bi and Ra2 and R 2 together are
, Ra3 is H, and b3 is CH3. In some variations of formula (25) described in the paragraphs above in which oi is 3, ai and ¾i and Ra2 and i,2 together are ancf ¾a3 ancf j¾b3 are
In some variations of formula (25) described in the paragraphs above in which o} is 3,
Rai and R¾i and Ra2 and Rb2 together are
Figure imgf000221_0006
[676] In variations of formula (25) described in the paragraphs above in which oj is 4, the three instances of Ra and are indicated as Rai and Rbi; a2 and Rb2; Ra3 and 3; and 34 and R¾4, respectively. In some variations of formula (25) described in the paragraphs above in which o} is 4, In some variations of formula (25) described in the paragraphs above in which o} is 4, each of RaS,RM, Ra2, j,2, Ra3, ¾>3, Ra4, and &4 is H. In some variations of formula (25) described in the paragraphs above in which oj is 4, each of ai, su, a2, b¾ a3, Rb3, Ra4, and is CH3. In some variations of formula (25) described in the paragraphs above in which o} is 4, each of Rai, M, R 2, b2, a3, and R¾3 is H and each of R34 and Rb4 is CH3. In some variations of formula (25) described in the paragraphs above in which o} is 4, each of Rai, M, Ra2, and Rb2 is H and each of Ra3, ¾>3, RA4, and RM I S CH3. In some variations of formula (25) described in the paragraphs above in which oi is 4, each of Rai, RM, Ra2, i>2, Ra3, and Rb3 is CH3 and each of
Figure imgf000222_0001
[677] In some variations of formula (25) described in the paragraphs above in which o} is 4, each of Rai,Ra2, and A3 is H and each of M, 2, and Rb3 is CH3. In some variations of formula (25) descri bed in the paragraphs above in which os is 4, Rai is H, R*i is CH3, and each of R¾2, Rb2, Ra3, and Rb3 is CH3. In some variations of formula (25) described in the paragraphs above in which o} is 4, Rai is H, M is CH3, and each of Ra2, R¾2, Ra3, and Rb3 is H. In some variations of formula (25) described in the paragraphs above in which oj is 4, each of Raj and a2 is H, each of M and ^ is CH3, and each of R^ and Rb3 is H. In some variations of formula (25) described in the paragraphs above in which o > i s 4, each of Rai and R.^ is H, each of M and j,2 is CH3, and each of Ra and ^? is CH .
[678] In some variations of formula (25) described in the paragraphs above in which oi is 4,
Rai and M are H, Ra2 and j>2 are H, R^ and R^ are H, and Ra4 and R1(4 are "^- ^ . In some variations of formula (25) described in the paragraphs above in which ο,- is 4, ai and M are H,
Ra2 and Rb2 are H, Ra3 and Rb3 are CH3, and Ra4 and Rb4 are . In some variations of formula (25) described in the paragraphs above in which oj is 4, Raj and ¾i are H, Ra2 and R¾
Figure imgf000222_0002
are CH3, . In some vari ations of formula (25) described in the paragraphs above in which oj is 4, ai and M are CH3, RA2 and ¾2 are CH3,
Ra3 and j,3 are CH3, and Ra4 and M are w .
[679] In some variations of formula (25) described in the paragraphs above in which o/ is 4,
Rai and are H, Ra2 and Rb2 are H, Ra3 and Rb3 are , and Ra4 and i,4 are
Figure imgf000222_0003
. In some variations of formula (25) described in the paragraphs above in which oj is 4, Rai and are H, ^ and Rj,2 are CH3, Ra3 and j,3 are ""*· ·?* , and RA4 and M are ¾r" . In some variations of formula (25) described in the paragraphs above in which o} is 4, Rai and Rw are
CH3, a2 and ¾2 are CH3, Ra3 and RB3 are '¾ , and Ra4 and R1(4 are " . In some variations of formula (25) described in the paragraphs above in which o} is 4, Rai is H, j>i is CH3, Ra2 and
Rb2 are CH3, Ra3 and R^ are ^ , and Ra4 and RM are "¾ ^ . In some variations of formula (25) described in the paragraphs above in which o,< i s 4, RAJ is II, RM is CII3, RA2 is H, Κ¾2 is
CH3, A3 and Rj,3 are '¾ ^\ and Ra4 and ¾4 are ' *· ^\
[680] In some variations of formula (25) described in the paragraphs above in which is 4,
Figure imgf000223_0001
Rai and RM are H, Ra2 and Rj,2 are "^- Ra3 and j)3 are "¾ and Ra4 and Rj>4 are some variations of formula (25) described in the paragraphs above in which o/ is 4, Ra3 and
Figure imgf000223_0002
are CH3, Ra2 and ¾2 are ' - Ra3 and I¾3 are In some variations of formula (25) described in the paragraphs above in which oj is 4, RAL i s H, t,i is
CH3, a2 and j,2 are S£ Ra3 and ¾3 are '¾S£ and Ra4 and t,4 are " V¾Si . In some variations of formula (25) described in the paragraphs above in which o}_ is 4, Rai and M are < - ; and Rb2 are N£ Ra3 and Rb3 are χ¾·S£ and RA4 and Rj> are ^ .
[681] In some variations of formula (25) described in the paragraphs above i which o/ is 4,
Rai and Rj,i are H, Ra2 and Rj,2 are H, Ra3 and j)3 are H, and Ra4 and R are
Figure imgf000223_0003
. In some variations of formula (25) described in the paragraphs above in which o is 4, RAJ and j,t are H,
O
Ra2 and RM are II, Ra3 and t,3 are CH3, and Ra4 and R¾4 are '¾· . In some variations of formula (25) described in the paragraphs above in which oi is 4, Ra! and J,J are H, Ra2 and I¾>2 are CH3, aj and RM are CH3, and Ra4 and R¾4 are
Figure imgf000223_0004
. In some variations of formula (25) described in the paragraphs above in which oj is 4, ai and M are CH3, Ra2 and s>2 are CH3,
A -
Ra3 and (,3 are CH3, and Ra4 and R¾,4 are . [682] In some variations of formula (25) described in the paragraphs above in which oi is 4,
O
Riii and M are H, Ra2 and R^ are H, Ra3 and Rt>3 are and RA4 and &4 are v. In some variations of formula (25) described in the paragraphs above in which o; is 4, Rai and M are H,
O O
Ra2 and Rt>2 are CH3, Ra3 and Rj>3 are "^- and Ra4 and are "^- In some variations of formula (25) described in the paragraphs above in which o; is 4, Ral and M are CH3, Ra2 and
O O
b2 are CH3, Ra and R|>3 are ^\ and Ra4 and are '¾· In some variations ot formula (25) described in the paragraphs above in which oj is 4, Ra} is H, j,i is CH3, Ra2 and Rb2 are
O O
¾A U-U
CH3, Ra3 and ¾3 are and A4 and ¾4 are ? . In some variations of tormula (25) described in the paragraphs above in which oj is 4, Raj is H, Rbj is CH3, Ra2 is H, ¾2 is CH3, A3 and B3 are
Figure imgf000224_0001
[683] In some variations of formula (25) described in the paragraphs above in which oi is 4,
Rai and i are H, Ra2 and R 2
Figure imgf000224_0002
In some variations of formula (25) described in the paragraphs above in which oj is 4, Rai and Rbi are CH3, Ra2 and Rb2 are
Figure imgf000224_0003
In some variations of formula (25) described in the paragraphs above in which o; is 4, Rai is H, R¾i is
CH3, Ra2 and R¾,2 riations of formula (25) de
Figure imgf000224_0004
scribed in the paragraphs above in which o > is 4, Ra3 and i are Ra2 and Rb2 are
Figure imgf000224_0005
.
[684] In some variations of formula (25) described in the paragraphs above in which o > is 4,
O
ai and R¾i are '¾ , Ra2 and ¾2 are H, Ra3 and ¾3 are H, and Ra4 and R 4 are *f" . In some variations of formula (25) described in the paragraphs above in which o i is 4, Raj and i O
are '¾*0 ^* , Ra2 and .b2 are CH3, aj and ¾3 are CH3, and RA4 and R¾4 are f\ In some variations of formula (25) described in the paragraphs above in which o,- is 4, ai and Rbi are
Q
" 0 *· , Ra2 and ¾2 are H, Ras and j,3 are CH3, and Ra4 and ¾4 are 00.
[685] In some variations of formula (25) described in the paragraphs above in which o, is 4,
Rai and Rbi are ' <· ^\ a2 and &2 are '¾ , Ra3 and R^s are H, and Ra4 and Rb4 are '¾· < . In some variations of formula (25) described in the paragraphs above in which oj is 4, Rai and ¾i
< ~"7 — 7 O
are " 0¾ , A2 and Rj,2 are 0 '¾ Ra3 and Rj>3 are CH3, and Ra4 and Rj,4 are 00 In some variations of formula (25 described in the paragraphs above in which o; is 4 Rai and M are
¾ , Ra2 and Rt>2 are
Figure imgf000225_0001
. In some variations of formula (25) described in the paragraphs above in which o; is 4, Rai and ^ are
, a2 and ¾2 are ' *· ^\ and RM axe II, and Ra and ^ are 0 ^\
[686] In some variations of formula (25) described in the paragraphs above in which o/ is 4, ai and Rbi are " w <~ Ra2 and j,? are w , Ra3 and Rb3 are ' w¾ , and Ra4 and Ljj,4 are
Figure imgf000225_0002
[687] In some variations of formula (25) described in the paragraphs above in which o i is 4,
— O O
Rai and Rw are ' 0*·0 Ra2 and b2 are '¾·k*5 Ra3 and Rb3 are H, and Ra4 and M are *"¾-0 , In some variations of formula (25) described in the paragraphs above in which o} is 4, Rai and Rbi
O O
are "*· ^" , Ra2 and ¾ are 0 ' «·0 ^ and Rj,3 are C¾, and Ra4 and ¾4 are 0 ^\ In some variations of formula (25) described in the paragraphs above in which oi is 4, Rai and Rbi are
O O
- 0¾0 ^ Ra2 an£| iib2 are 0 ' ^- ¾a3 anc Rb3 are CH3, and Ra4 and j,4 are ·■0. In some variations of formula (25) described in the paragraphs above in which oi is 4, Rai and Rj>i are
O O
-¾ f- ^ Ra2 an£j iib2 are ' ¾a3 anc Rb3 are anc| ]¾a4 anc| ¾b4 are -\ .
[688] In some variations of formula (25) described in the paragraphs above in which o} is 4,
½1 and Rj,i are
Figure imgf000226_0001
o
[689] In some variations of formula (25) described in the paragraphs above in which oj is 4,
Rai and
Figure imgf000226_0002
. In some variations of formula (25) described in the paragraphs above in which oj is 4, Rai and J¾,i
Figure imgf000226_0003
variations of formula (25) described in the paragraphs above in which o is 4, RaJ and RbJ are
Figure imgf000226_0004
In some variations of formula (25) described in the paragraphs above in which o is 4, RaJ and Rj,j are
0 0 O
'¾· a2 and j,2 are ' - Ra3 and R1( are H, and Ra4 and ^ are ' *· .
[690] In some variations of formula (25) described in the paragraphs above in which o > is 4,
Rai and R¾i are
Figure imgf000226_0005
[691] In some variations of formula (25) described in the paragraphs above in which o i is 4,
Rai and M are H, Ra2 and (,2 are H, and Ra3 and j,3 and Ra4 and j,4 together are . In some variations of formula (25) described in the paragraphs above in which oj is 4, Rai and j,i are H, Ra2 and j>2 are CH3, and Ra3 and Rj>3 and Ra4 and j,4 together are . In some variations of formula (25) described in the paragraphs above in which o; is 4, Rai and Ra2 are H,
Rbi and i>2 are CH3, and Ra3 and j,3 and Ra4 and M together are ' . [692] In some variations of formu described in the paragraphs above in which oi is 4,
Rai and R¾i are H, Ra2 and R¾2 are
Figure imgf000227_0001
and RA3 and Rj,3 and A4 and R¾4 together are
^1- V In some variations of formula (25) described in the paragraphs above in which o} is 4,
Rai and M are '¾· Ra2 and j,2 are CH3, and Raj and j,3 and Ra4 and R¾4 together are ""^ V In some variations of formula (25) described in the paragraphs above in which o , is
1Λι is H, Rbi is CH3, Ra2 lb2 are , and Ra3 and j,? and Ra4 and M together are
[693] In some variations of formula (25) described in the paragraphs above in which o, is 4,
Rai and M are H, Ra2 and (,2 are "¾ A· ^_ anc[ Ra3 an(f ¾3 an(f Ra4 ancj Rb4 together are '¾^N^¾ In some variations of formula (25) described in the paragraphs above in which oi is 4, Rai and
0
Rbi are "*· Ra2 and Rj,2 are CH3, and R¾3 and j,3 and RA and R¾ together are ^ V In some variations of formula (25) described in the paragraphs above in which o} is 4, RaS is H, Rbi
O
is CH3, Ra2 and Ri)2 are ^ and Ra3 and j>3 and Ra4 and j>4 together are '¾ z .
[694] In some variations of formula (25) described in the paragraphs above in which o/ is 4,
O O
Rai and Rj,i axe ¾ "^A- jf Ra2 and j)2 are ¾ '^A- and and R¾3 and Ra4 and RM together are . In some variations of formula (25) described in the paragraphs above in which o i is 4,
Figure imgf000227_0002
. In some variations of formula (25) described in the paragraphs above in which o} is 4,
Rai and bi are
Figure imgf000227_0003
5] In some variations of formula 25 described in the paragraphs above in which o i is 4,
Rai and R¾i are
Figure imgf000228_0001
, Ra2 and t,2 are and Raj and ¾3 and RA4 and M together are
[696] In some variations of formul a (25) described in the paragraphs above in which o} is 4, ai and M and Ra2 and Rj,2 together are ""^- ¾ , and Ra3 and j,3 and Ra4 and j>4 together are
[697] In some variations of formul a (25) described in the paragraphs above in which o? is 1, RAI and Rj,i are both H. In some variations of formula (25) described in the paragraphs above in which o? is 1, Rai is H and M is CH3. In some variations of formula (25) described in the paragraphs above in which o2 is 1, Rai and R¾i are both CH3. In some variations of formula (25) described in the paragraphs above in which <¾ is 1 , Rai and j>i are "*· , In some variations of
O
formula (25) described in the paragraphs above in which o2 is 1, ai and Rj>i are ^\
[698] In variations of formula (25) described in the paragraphs above in which o2 is 2, the two instances of Ra and I¾ are indicated as ai and M and Ra2 and j,?, respectively. In some variations of formula (25) described in the paragraphs above in which o2 is 2, each of Rai and bi and Ra2 and R^ is H. In some variations of formula (25) described in the paragraphs above in which o2 is 2, each of RaJ and j,t and Ra2 and Rj,2 is CH3. In some variations of formula (25) described in the paragraphs above in which o2 is 2, each of Rai and Ra2 is H and each of M and Rb2 is CH3. In some variations of formula (25) described in the paragraphs above in which o2 is 2, each of Rai, Rai, and RM is H and Ι½ is CH3.
[699] In some variations of formula (25) described in the paragraphs above in which o2 is 2, each of Rai and RM is H and Ra2 and ¾2 are "¾ . In some variations of formula (25) described in the paragraphs above in which o2 is 2, each of ai and i»i is H and Ra2 and R¾2 are O
'¾· . In some variations of formula (25) described in the paragraphs above in which o2 is 2, each of Rai and RM i s CH3 and
Figure imgf000228_0002
. In some variations of formula (25) described in the paragraphs above in which o2 is 2, each of ai and ¾i is CH3 and Ra2 and Rj,2
Figure imgf000229_0001
are
In some variations of formula (25) described in the paragraphs above in which o2 is 2, Rai is H, is (Ί f and Ra2 and Rj>2 are '¾ . In some variations of formula (25) described in the
O
paragraphs above in which o2 is 2, ai is H, is CH3, and Ra2 and j)2 are ¼A , in some variations of formula (25) described in the paragraphs above in which o2 is 2, Rai and R^ and
Ra2 and R¾2 together ar ns of formula (25) described in the paragraphs
Figure imgf000229_0002
above in which o2 is 2, and R¾2 are ^\ In some variations of formula (25) described in the paragraphs above in which o2 is 2, Rai and j,i are '¾ Ra2 and
O
Rb2 are ¾ -A ^ . In some variations of formula (25) described in the paragraphs above in which o2
O O
is 2, Ra! and R¾i are % R^ and ¾2 are "¾A·
[700] In variations of formula (25) described in the paragraphs above in which o2 is 3, the three instances of Ra and Rj, are indicated as ai and j,i; Ra2 and ¾,2; and A3 and Rj,3, respectively. In some variations of formula (25) described in the paragraphs above in which o2 is 3, In some variations of formula (25) described in the paragraphs above in which o2 is 3, each of Rai,Rt>i, Ra2, R¾2, a3, and ¾s is H. In some variations of formula (25) described in the paragraphs above in which o? is 3, each of Rai,Rbi, Ra2, ¾2, Raj, and b is CH3. In some variations of formula (25) described in the paragraphs above in which o2 is 3, each of Rai,Rbi, Ra2, and ¾2, is H and each of Ra3 and ^ is CH3. In some variations of formula (25) described in the paragraphs above in which o2 is 3, each of Raj,Rt>i, a2, and t,2, is CH3 and each of as and ^ is H. In some variations of formula (25) described in the paragraphs above in which o2 is 3, Rai is H and each of Ra2, A3, Rbi , 2, and H^s is CH3. In some variations of formula (25) described in the paragraphs above in which o2 is 3, each of Rai and Ra2 is H and each of RA3, RM, RM, and R¾3 is CH3. In some variations of formula (25) described in the paragraphs above in which o2 is 3, each of Rai, Ra2, and 33 is H and each of RM, ¾2, and b3 \s O \ . ] In some variations of formula (25) described in the paragraphs above in which o2 is 3 each of Rai,¾i, Ra2, an J¾,2, is H and a3 and ¾3 are w "¾ . In some variations of formula (25) described in the paragraphs above in which o2 is 3, each of Rai,Rbi, Ra2, and Rb2, is CH3 and Ra3 and Rb3 are "^- . In some variations of formula (25) described in the paragraphs above in which o2 is 3, Rai is H and each of Ra2, bi, and Rb2 is CH3, and Ra3 and Rb3 are "¾ . In some variations of formula (25) described in the paragraphs above in which o2 is 3, each of Ra3 and
Ra2 is H and each of bi and Rb2 is CH3, and a3 and Rb3 are "¾ .
[702] In some variations of formula (25) described in the paragraphs above in which o2 is 3,
O
each of Rai,Rbi, Ra2, and Rb2, is H and R^ and Rb3 are . In some variations of formula (25) described in the paragraphs above in which o2 is 3, each of ai,Rw, Ra2, and Rb2, is CH3 and Ra3
O
and Rb3 are ^\ In some variations of formula (25) described in the paragraphs above in which
O
o2 is 3, Rai is H and each of R^, Rb}, and Rb2 is C¾, and R^ and ¾3 are ' <- < . In some variations of formula (25) described in the paragraphs above in which o2 is 3, each of Rai and
O
Ra2 is H and each of bi and Rb2 is CH3, and a3 and Rb3 are .
[703] In some variations of formula 25 described in the paragraphs above in which o2 is 3, Rai and RbS are
Figure imgf000230_0001
Ra2 and Rb2 are and each of Ras and Rb3 is H. In some variations of formula (25) described in the paragraphs above in which o2 is 3, Rai and bi are '¾ Ra2 and R 2 are L and each of Ra3 and R 3 is CH3. In some variations of formul (25) described in the paragraphs above in which o2 is 3, Rai and bi are "¾ , Ra2 and Rb2 are
Figure imgf000230_0002
, Ra3 is H, and Rb3 is CH3. In some variations of formula (25) described in the paragraphs above in which o2 is 3, Rai and Rbi are " ^ , Ra2 and Rb2 are "¾ , and each of Ra3 and Rb3 is H.
some variations of formula (25) described in the paragraphs above in which o2 is 3, Ra3 and ,¾ ,ν,
are , Ra2 and Rj,? are "¾ , and each of Ra3 and Rb3 is CH3. In some variations of formula
15)" described in the paragraphs above in which o2 is 3, Raj and Rt>i are "¾ , Ra2 and I¾>2 are
Figure imgf000231_0001
[704] In some variations of formula (25) described in the paragraphs above in which o2 is 3,
— j
X
Rai and Rbi are '¾· . Ra2 and Rj,2 are ' lΑ- <* and each of aj and j,3 is II. In some variations of formula (25) described in the paragraphs above in which o2 is 3, Rai and Rbi are "¾ "^ , Ra2
O
and j,2 are *\ and each of a3 and b3 is CH3. In some variations of formula (25) described
O
w ¾A<* in the paragraphs above in which o2 is 3, ai and R¾i are '¾ , Ra2 and ¾2 are Ra3 is H, and Rb3 is CH3. In some variations of formula (25) described in the paragraphs above in which o2
O
is 3, ai and R¾i are '¾ ^\ Ra2 and Rb2 are '¾· f" , and each of aj and ^ is H. In some variations of formula (25) described in the paragraphs above in which o2 is 3, Rai and i are and each of Ra3 and b3 is CH3. In som
(
Figure imgf000231_0002
25) described in the paragraphs above in which o2 is 3, Ra3 and Rbj a re O
Figure imgf000231_0003
[70S] In some variations of formula (25) described in the paragraphs above in which o2 is 3,
O O
Rai and bi are ¾A ^ <**, Ra2 and ¾2 are ¾ '¾A· «i , and each of aj and ¾3 is H. In some variations of
O
formula (25) described in the paragraphs above in which o2 is 3, Rai and i are ¾Ai Ra2 and
O
Rb2 are ¾ A and each of a3 and b3 is CH3. In some variations of formula (25) described in the paragraphs above in which o2 is 3, ai and ¾ι are
Figure imgf000231_0004
Ra3 is II, and Rbsis CH3. In some variations of formula (25) described in the paragraphs above in which o2
O O
is 3, Hal and ¾i are Ra2 and Rb2 are "»- and each of ¾3 and Rb3 is H. In some variations of formula (25) described in the paragraphs above in which o2 is 3, Rai and M are O O
-\ and Rb2 are and each of RA3 and Rb3 is CH3. In some variations of formula (25)
O O
described in the paragraphs above in which o? is 3, ai and M are · Ra2 and Rb2 are -
Figure imgf000232_0001
i] In some variations of formula (25) described in the paragraphs above in which o2 is 3,
Rai and Rm and Ra2 and i»2 together are '¾ s/¾3 and each of A3 and R^is H. In some variations of formula (25) described in the paragraphs above in which o2 is 3, Rai and !¾ and
Ra2 and R(,2 together are "^- and each of A and bsis CH3. In some variations of formula (25) described in the paragraphs above in which o2 is 3, Rai and M and Ra2 and R2 together are V V
, Ra3 is H, and ^ is CH3. In some variations of formula (25) described in the paragraphs above in which o? is 3, ai and ¾i and Ra2 and i,2 together are , and RA3 and Rb3 are
In some variations of formula (25) described in the paragraphs above in which o2 is 3,
O
Rai and R¾i and Ra2 and j,2 together are , and as and j>3 are ' *· ^\
[707] In variations of formula (25) described in the paragraphs above in which o2 is 4, the three instances of Ra and j> are indicated as Rai and ¾i; Ra2 and Rj,2; Ra3 and Rj,3; and 34 and R¾4, respectively. In some variations of formula (25) described in the paragraphs above in which o2 is 4, In some variations of formula (25) described in the paragraphs above in which o2 is 4, each of Rai,¾i, ¾2, ¾2, ¾3, ¾3, Ra4, and M is H. In some variations of formula (25) described in the paragraphs above in which o2 is 4, each of Κ»ί,¾ι, ϊ¾ , ¾2, Ra3, ¾3, Ra , and M is CH3. In some variations of formula (25) described in the paragraphs above in which o2 is 4, each of Rai, Rbi, Ra2, Rb2, R 3, and &sis H and each of A4 and Rb4is CH3. In some variations of formula (25) described in the paragraphs above in which o2 is 4, each of Rai, M, Ra2, and I½ is H and each of Ra , ¾3, RA4. and ^is CH3. In some variations of formula (25) described in the paragraphs above in which o2 is 4, each of Rai, M, a2, R¾2, a, and ^is CH3 and each of Ra4 and ^is H. 8] In some variations of formula (25) described in the paragraphs above in which o2 is 4, each of Rai,Ra2, and Ra3 is H and each of w, Rb2, and Rb3 is CH3. In some variations of formula (25) described in the paragraphs above in which <¾ is 4, Rai is H, Rbi is CH3, and each of Ra2, R 2, Ra3, and R is (Ί . In some variations of formula (25) described in the paragraphs above in which o2 is 4, aj is H, RM is CH3, and each of Ra2, Rb2, a3. and Rb3 is H. In some variations of formula (25) described in the paragraphs above in which o2 is 4, each of Rai and Ra2 is H, each of Rw and Rb2 is CH3, and each of ^ and Rb3 is H. In some variations of formula (25) described in the paragraphs above in which o2 is 4, each of Ral and is H, each of Rbi and Rb2 is CH3, and each of a3 and R 3 is CH3.
[709] In some variations of formula (25) described in the paragraphs above in which o2 is 4,
Rai and RM are H, Ra2 and RB2 are H, and RB3 are H, and Ra4 and Rb4 are '¾ ^ , In some variations of formula (25) described in the paragraphs above in which o2 is 4, Rai and RM are H,
Ra2 and Rb2 are H, Ra3 and Rb3 are CH3, and a4 and R 4 are "¾ . In some variations of formula (25) described in the paragraphs above in which o2 is 4, Rai and bi are H, Ra2 and are CH3, as and R 3 are CH3, and Ra4 and b4 are " L . In some variations of formula (25) described in the paragraphs above in whic is 4, Raj and i are CH3, Ra2 and Rb2 are CH3, and RB3 are CH3, and Ra4 and Rb4 are
Figure imgf000233_0001
[710] In some variations of formula (25) described in the paragraphs above in which o? is 4,
Figure imgf000233_0002
Raj and Rbj are H, Ra2 and Rb2 are H, ^ and R 3 are "*· and a4 and R 4 are . In some variations of formula (25) described in the paragraphs above in which o2 is 4, Rai and Rbi are H, Ra2 and Rb2 are CH3, Ra3 and Rb3 are '¾ and Ra4 and Rb4 are ^ . In some variations of formula (25) described in the paragraphs above in which o2 is 4, Rai and Rbi are
O . Ra2 and R¾>2 are CH3, Ra3 and Rb3 are "^- and Ra4 and Rb4 are "^- . In some variations of formula (25) described in the paragraphs above in which o2 is 4, Ral is H, Rbi is CH3, Ra2 and are CH3, Ra3 and R 3 are ' *· , and Ra4 and Rb4 are " . In some variations of formula (25) described in the phs above in which is 4, Rai is H, ¾i is CH3, RA2 is H, R¾2 s
CH3, Ra3 and R ,3 are
Figure imgf000234_0001
and RA4 and RM are
[711] In some variations of formula (25) described in the paragraphs above in which o2 is 4,
Rai and R¾i are H, Ra2 and R¾2 are VN£ RA3 and ¾3 are " V¾N ^i" , and RA4 and R¾4 are '¾ ^ί . In some vari ations of formula (25) described in the paragraphs above in which o2 is 4, RaS and R¾i are CH3, and Rb2 are "¾ , Ra3 and ^ are "¾ , and Ra4 and ^ are "*· . In some variations of formula scribed in the paragraphs above in which o2 is 4, Rai is H, R|>i is
CH3, Ra2 and ¾2 are
Figure imgf000234_0002
Ra3 and R 3 are '¾· and RA4 and Rj, are . In some variations of formula (25) described in the paragraphs above in which <¾· is 4, RAJ and RJ,J are
. _ w
"¾ Ra2 and Rb2 are '¾ Ra3 and R^ are "^- ^\ and Ra4 and Rj,4 are '¾ ^\
[712] In some variations of formula (25) described in the paragraphs above in which o2 is 4,
O
Rai and Rt>i are H, Ra2 and Rb2 are H, ^ and j,? are H, and R^ and ¾ are . In some variations of formula (25) described in the paragraphs above in which o? is 4, Ral and j,i are H,
O
Ra2 and Rj,2 are H, A3 and j,3 are CH3, and RA and M are A · ^c-* . In some variations of formula (25) described in the paragraphs above in which o2 is 4, aj and j,i are H, Ra2 and R¾,2
O
are CH3, aj and j, are CH3, and RA and R are s A· e . In some variations of formula (25) described in the paragraphs above in which o2 is 4, ai and RM are CH3, Ra2 and R¾,2 are CH3,
A '
Ra3 and t,3 are CH3, and 34 and R¾4 are .
[713] In some variations of formula (25) described in the paragraphs above in which o2 is 4,
O
Ra3 and M are H, Ra2 and Rb2 are H, ^ and j,3 are "*· and Ra4 and M are v. In some variations of formula (25) described in the paragraphs above in which o2 is 4, Ral and Rj,i are H,
A A
Ra2 and ¾2 are CH3, as and ^ are "¾· and Ra4 and RM are In some variations of formula (25) described in the paragraphs above in which o2 is 4, Rai and Rbi are CH3, a2 and
O O
Rb2 are CH3, RA3 and ¾ are "^- and A4 and ¾4 are ^\ In some variations of formula (25) described in the paragraphs above in which o2 is 4, RAS is H, RM is CH3, Ra2 and Rb2 are CH3, RA3 and R¾,3 are
Figure imgf000235_0001
In some variations of formula (25 ) described in the paragraphs above in which o2 is 4, RA3 is II, RB! is CH3, RA2 is H, 2 is CH3,
Figure imgf000235_0002
[714] In some variations of formula (25) described in the paragraphs above in which o2 is 4,
0 0 0
¾A <* ¾A / ¾A
Rai and bi are II, a2 and b2 are'¾- a3 and 3 are 'h- i , and RA4 and RB4 are'¾- . In some variations of formula (25) described in the paragraphs above in which o2 is 4, ai and Rbi are CH3, a2 and b2 are
Figure imgf000235_0003
In some variations of formula (25) described in the paragraphs above in which o2 is 4, Rai is H, i is
Figure imgf000235_0004
In some variations of formula (25) described in the paragraphs above in which o2 is 4, RAI and bi are
Figure imgf000235_0005
and Rb2 are
Figure imgf000235_0006
[715] In some variations of formula (25) described in the paragraphs above in which o? is 4,
Rai and R i are
Figure imgf000235_0007
. In some variations of formula (25) described in the paragraphs above in which o2 is 4, ai and bj are
Figure imgf000235_0008
In some variations of formula (25) described in the paragraphs above in which o2 is 4, ai and bi are
r— 7 O
"¾ a2 and RB2 are H, a3 and 3 are CH3, and RA4 and RB4 are '¾· ? [716] In some variations of formula (25) described in the paragraphs above in which o? is 4,
Riii and M are Ra2 and n,? are "% ¾3 and Rb3 are H, and RA4 and Rj,4 are '^- <*\ In some variations of formula (25) described in the paragraphs above in which o2 is 4, RaS and R¾i
Figure imgf000236_0001
In some variations of formula (25) described in the paragraphs above in which o2 is 4, Rai and j,i are
Figure imgf000236_0002
'¾ a2 and j,2 are ' *· ^* . In some variations of formula (25) described in the paragraphs above in which o2 is 4, ai and M are
O
"¾ , a2 and R¾2 are , aj and ¾3 are H, and Ra4 and are '¾· .
[717] In some variations of formula (25) described in the paragraphs above in which o2 is 4,
Rai and RM are '^-NC Ra2 and j,2 are N ^i , Ra3 and Ι¾,3 are % and Ra4 and Rb4 are
O
[718] In some variations of formula (25) described in the paragraphs above in which o? is 4,
O O
Rai and Rbi are "¾ Ra2 and are Ra3 and j>3 are H, and Ra4 and Rb4 are ^ . In some variations of formula (25) described in the paragraphs above in which o2 is 4, ai and j,i
O O
are " ^ , Ra2 and Rj,2 are '^- ^ and I¾>3 are CH3, and Ra4 and ¾4 are ^\ In some variations of formula (25) described in the paragraphs above in which o is 4, Rai and M are
"¾ G , Ra2 and j)2 aie
Figure imgf000236_0003
In some variations of formula (25) described in the paragraphs above in which o2 is 4, as and RM are
O O
"¾ Ra2 and Rj>2 are % · Ra3 and are H, and Ra4 and R1( are % A· ^ , [719] In some variations of formula (25) described in the paragraphs above in which o? is 4,
Riii and R i are
Figure imgf000237_0001
and Rb4 are
O
[720] In some variations of formula (25) described in the paragraphs above in which o? is 4,
Rai and Rbi are
Figure imgf000237_0002
. In some variations of formula (25) described in the paragraphs above in which o2 is 4, Rai and R i are
Figure imgf000237_0003
variations of formula (25) described in the paragraphs above in which o is 4, Rai and bi are 0 0 o
A A A
'¾· <* a2 and Rb2 are "¾ Ra3 and Rb3 are CH3, and Ra4 and M are ^ . In some variations of formula (25) described in the paragraphs above in which o2 is 4, Rai and bi are 0 0 o
¼· Ra2 and Rb2 are ½ Ra3 and Rb3 are H, and Ra4 and Rb4 are
[721] In some variations of formula (25) described in the paragraphs above in which o is 4,
Figure imgf000237_0004
[722 ] In some variations of formula (25) described in the paragraphs above in which o2 is 4,
Ra3 and Rb3 are H, Ra2 and Rb2 are H, and Ra3 and Rb3 and Ra4 and Rb4 together are . In some variations of formula (25) described in the paragraphs above in which o2 is 4, Rai and i are H, R^ and Rb2 are CH3, and Ra3 and Rj,3 and Ra4 and Rb4 together are ' L . In some variations of formula (25) described in the paragraphs above in which o? is 4, Ral and Ra2 are H,
Rbi and Rb2 are CH3, and and Rb3 and Ra4 and Rb4 together are [723] In some variati ons of formula (25) described in the paragraphs above in which o? is 4,
Raj and j are H, Ra2 and R 2 are '¾ and a3 and 3 and Ra4 and R 4 together are . In some variations of formula (25) described in the paragraphs above in which o2 Rai and Rbj are " Ra2 and Rb2 are CH3, and Ra3 and Rb3 and Ra4 and Rb4 together are ' ¾ . In some variations of formula (25) described in the paragraphs above in which o2 is 4,
Ra3 is H, RbJ is CI¾, Ra2 and Rb2 are '¾ , and Ra3 and Rb3 and Ra4 and Rb together are
[724] In some variations of formula (25) described in the paragraphs above in which o? is 4,
O
Rai and R¾i are H, Ra2 and R 2 are and Ra3 and R 3 and Ra4 and Rb4 together are L ,
In some variations of formula (25) described in the paragraphs above in which o2 is 4, Ra! and
9
bi are "*· Ra2 and R 2 are CH3, and a3 and R 3 and Ra4 and R 4 together are ¾ V In some variations of formula (25) described in the paragraphs above in which o? is 4, Rai is H, R i is CH3, Ra2 and Rh2 are
Figure imgf000238_0001
and Ra3 and Rb3 and Ra4 and Rb together are ¾ V
[725] In some variations of formula (25) described in the paragraphs above in which o? is 4, and Rb3 and Ra4 and R 4 together
Figure imgf000238_0002
In some variations of formula (25) described in the paragraphs above in which o? is 4, and Ri,i are
Figure imgf000238_0003
Ra2 and Rb2 are and Ra3 and R 3 and Ra and Rb together are . In some variations of formula (25) described in the paragraphs above in which o2 is 4,
O O
% A/ A
Rai and Rb3 are '¾· Ra2 and Rb2 are - ^\ and ^ and Rb3 and Ra and Rb together are
[726] In some variations of formula (25) described in the paragraphs above in which o? is 4,
Rai and Rbj are "¾ Ra2 and Rb2 are
Figure imgf000238_0004
and Ra3 and Rb3 and Ra and Rb4 together are [727] In some variations of formula (25) described in the paragraphs above in which <¾> is 4, Riii and ¾i and Ra2 and Rj>2 together are "¾ and R¾3 and b3 and Ra4 and R^ together are
[728] In some variations of formula (25) described in the paragraphs above, ring A is optionally substituted with halo or C1 -C6 linear or branched alkyl;
Figure imgf000239_0002
optionally substituted with halo or C1 -C6 linear or branched alkyl; or
Figure imgf000239_0003
Figure imgf000240_0001
optionally substituted with halo or C 1-C6 linear or branched alkyl.
[730] In some variations of formula (25) described in the paragraphs above, n is 1-4, 1-3, 1-2, 2-4, 2-3, 3-4, I, 2, 3, or 4.
[731] In some variations of formula (25) described in the paragraphs above, ring A is substituted with halo. In some variations, the halo is F, Br, I, or Ci.
[732 ] In some variations of formula (25) described in the paragraphs above, ring A is substituted with C 1-C6 linear or branched alkyl (e.g., C 1-C6, C1-C5, C 1-C4, C1-C3, C 1-C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl).
[733] In some variations of formula (25) described in the paragraphs above, 1)1 is safranin-O. In some variations of formula (25) described in the paragraphs above, the first D2 is safranin-O. In some variations of formula (25) described in the paragraphs above, the second 1)2 is safranin- O. In some variations of formula (25) described in the paragraphs above, Dl and the first D2 are safranin-O. In some variations of formula (25) described in the paragraphs above, Dl and the second D2 are safranin-O. In some variations of formula (25) described in the paragraphs above, the first D2 and the second D2 are safranin-O.
[734] In some variations of formula (25) described in the paragraph above, the pendant phenyl ring of Dl is unsubstituted. In some variations of formula (25) described in the paragraph above, the pendant phenyl ring of Dl is substituted with 1-3 (e.g., 1 -3, 1-2, 1 , 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— -NH2,— NHR,— NR2,— OH,— O",
— NHCOCH3,— NHCOR,— OCH3,—OR,— C2H5,— R, and— C6¾, wherein R is C 1-C6 linear or branched alkyl (e.g., C 1-C6, C 1-C5, C1-C4, C 1-C3, C1-C2, CI , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl ). In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— -NO2,— - R3 +, halo (e.g., F, Br, CI, I), trihalide (e.g.,— CF3,— CCI3,— CBr3, (' ! : )..— CN,— SO3H,— COOH,— COOR,— CHO, and — COR, wherein R is C1-C6 linear or branched alkyl (e.g., C 1 -C6, C 1-C5, C1 -C4, C 1-C3, C l- C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
[735] In some variations of formula (25) described in the two paragraphs above, the pendant phenyl ring of the first D2 is unsubstituted. In some variations of formula (25) described in the paragraph above, the pendant phenyl ring of the first D2 is substituted with 1-3 (e.g., 1-3, 1-2, 1, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of the first D2 is substituted, the substituents are selected independently from— NH2,— HR, — NR2, Oi l, 0\— NHCOCH3, --NHCOR,— -OCH3,—OR,— C2¾,— , and— C6H5, wherein is C 1-C6 linear or branched alkyl (e.g., C1-C6, C 1 -C5, C1-C4, C 1-C3, C 1 -C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of the first D2 is substituted, the substituents are selected independently from— -N02,— NR3 \ halo (e.g., F, Br, CI, I), trihalide (e.g.,— CF3,— CC13,— CBr3,— CI3),— CN,— SO3H,—COOH, — COOR,— CHO, and— COR, wherein R is C 1-C6 linear or branched alkyl (e.g., C1 -C6, Cl - C5, C 1-C4, C1-C3, C 1-C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). [736] In some variations of formula (25) described in the three paragraphs above, the pendant phenyl ring of the second D2 is unsubstituted. In some variations of formula (25) described in the paragraph above, the pendant phenyl ring of the second D2 is substituted with 1-3 (e.g. , 1 -3, 1 -2, 1, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of the second D2 is substituted, the substituents are selected independently from— H2,— -NHR, — NR2,—OH, ()",— NHCOCH3,— NHCOR,— OCH3,— OR, CM k— R, and— C6H5, wherein R is C1 -C6 linear or branched alkyl (e.g., C1-C6, C1 -C5, C1-C4, C1 -C3, C 1 -C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of the second D2 is substituted, the substituents are selected independently from— N02,— NR3 +, halo (e.g., !· . Br, CI, I), trihalide (e.g., ---CF3, ---CC13, --CBr3, --(¾),— CM, --S03H, --COOH, — COOR,— CHO, and— COR, wherein R is C 1-C6 linear or branched alkyl (e.g., C1 -C6, Cl- C5, C 1-C4, C1-C3, C1-C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl).
[737] In some of the variations of formul a (25) described above,, Dl and D2 are safranin-0 moieties, as shown in formula (25a):
Figure imgf000242_0001
(25a) in which m, n, //, ¾, ), o2, ring A, Rai, RM; Ra2, R¾2 Rci, RJI, Rd2, and ^ are as defined in the paragraphs above, Ri, R2, R3, ¾, R5, an ¾ independently are absent or independently are selected from— NH2,— HR,— NR?,—OH,— 0\— NHCOCH3,— NHCOR,— OCH3,— OR, — C2H5,— R,— ( ',·,! k— N02,—NR3 ÷, halo (e.g., F, Br, CI, I), trihalide (e.g.,— CF3,— CC13, — CBr3,— CI3),— CN,— SO3H,— COOH,—COOR,—CHO, and—COR), and R is C 1-C6 linear or branched alkyl (e.g., C 1-C6, C 1-C5, C1-C4, C 1-C3, C1-C2, CI , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). [738] One of skill in the art can readily visualize and prepare other catiomc mul timers falling within formula (25) in which other cationic dye moieties are used in place of one or both of the safranin-0 moieties, f 739] Some cationic dye multimers fall within formula (26), (27), (28), (29), (30), (31), or (32):
Figure imgf000243_0001
(30) (31
wherein D is a cationic dye moiety, nx is 0-5, ny is 1-5, and L is absent or L is a linker selected from linker (a.1), linker (a.2), linker (b. l), linker (c. l), linker (c.2), linker (d), linker (e. l), linker (f. 1), linker (f.2), linker (g. l), linker (g.2), linker (h. l), linker (h.2), linker (i. l), linker (i.2), linker (j. l), linker (j .2), linker (k), linker (i. l), linker (1.2), linker (m. l), linker (n. l), linker (n.2), linker (o), linker (p), linker (q), linker (r), and linker (s), described above. }] In some variations of formula (26), (27), (28), (29), (30), (31 ), or (32), L is linker (a. l):
Figure imgf000244_0001
, in which n is 1-6, ttj is 1-4, and * is the attachment site for the cationic dye moiety D.
[741] In some variations of formula (26), (27), (28), (29), (30), (31 ), or (32) in which L is linker (a. l), n is 1-6, 1-5, 1-4, 1-3, 1-2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, 5-6, 1, 2, 3, 4, 5, or 6.
[742 ] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (a. l), nj is 1-4, 1-3, 1-2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[743] In some variations of formula (26), (27), (28), (29), (30), (31), or (32), L is linker (a.2):
Figure imgf000244_0002
Ά-^ , in which n is 1-6, n} is 1-4, and * is the attachment site for the cationic dye moiety I),
[744] In some variations of formula (26), (27), (28), (29), (30), (31 ), or (32) in which L i s linker (a.2), n is 1-6, 1-5, 1-4, 1-3, 1-2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, 5-6, I, 2, 3, 4, 5, or 6.
[745] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (a.2), m is 1 -4, 1-3, 1-2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[746] In some variations of formula (26), (27), (28), (29), (30), (31), or (32), L is linker (b. l):
Figure imgf000244_0003
, in which « is 0-6, n} is 1 -4, and * is the attachment site for the cationic dye moiety D.
[747] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) in which L is linker (b. l), n is 0-6, 0-5, 0-4, 0-3, 0-2, 0-1, 1-6, 1-5, 1-4, 1-3, 1-2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3- 4, 4-6, 4-5, 5-6, 0, 1, 2, 3, 4, 5, or 6.
[748] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (b. l), ti] is 1-4, 1-3, 1-2, 2-4, 2-3, 3-4, 1 , 2, 3, or 4. [749] In some variations of formula (26), (27), (28), (29), (30), (31 ), or (32), L is linker (c. l):
Figure imgf000245_0001
, in which n is 0-6, n} is 1-4, either (1) Ra and ¾ independently are H or CH3
O
or (2) Ra and Rb are "^- or or (3) two of C aRb are and * is the attachment site for the cationic dye moiety D.
[750] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) in which L is linker (c. l), n is 0-6, 0-5, 0-4, 0-3, 0-2, 0-1, 1-6, 1-5, 1-4, 1-3, 1-2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3- 4, 4-6, 4-5, 5-6, 0, I, 2, 3, 4, 5, or 6.
[751] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (c. l), «/ is 1-4, 1-3, 1-2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[752] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (c. I), Ra is H and b is H. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (c. l), Ra is H and Rb is CH3. In some variations of formula (26), (27), (28), (29), (30), (31), or
(32) described in the paragraphs above in which L is linker (c. l), Ra and are '¾ . In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above
O
in which L is linker (c.1), Ra and R¾ are , In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (c.1), two of
CRaR¾ are ^^^ ,
[753] In some variations of formula (26), (27), (28), (29), (30), (31), or (32), L is linker (c.2):
Figure imgf000245_0002
, in which n is 0-6, «/ is 1-4, either (1) Ra and ¾ independently are H or CH3
— y o
or (2) Ra and Rb are " or '¾ or (3) two of CRaRb are ; and * is the attachment site for the cationic dye moiety D. [754] In some variations of formula (26), (27), (28), (29), (30), (31 ), or (32) in which L is linker (c.2), n is 0-6, 0-5, 0-4, 0-3, 0-2, 0-1, 1-6, 1-5, 1-4, 1-3, 1-2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3- 4, 4-6, 4-5, 5-6, 0, 1 , 2, 3, 4, 5, or 6.
[755] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (c.2), it} is 1 -4, 1-3, 1-2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[756] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (c.2), Ra is H and j, is H. In some variations of formula (26), (27), (28), (29), (30), (31 ), or (32) described in the paragraphs above in which L is linker (c.2), Ra is H and ¾ is Ct¾. In some variations of formula (26), (27), (28), (29), (30), (31), or
(32) described in the paragraphs above in which L is linker (c.2), Ra and ¾ are "¾ in some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above
O
in which L is linker (c.2), Ra and ¾ are "¾ ^\ In some variations of formula (26), (27), (28),
(29), (30), (31), or (32) described in the paragraphs above in which L is linker (c.2), two of CRaRb are
[757] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (c), L is ; ¾Tx^/ - ^ T**** ^^* ^^ ^
Figure imgf000246_0001
[758] In some variations of formula (26), (27), (28), (29), (30), (31), or (32), L is linker (d): — , where k is 2-10; (1) Ra and Rb independently are H or CH3, or (2) Ra and Rb are — j O
- i. or -\ f- ^ or (3) tw0 of CRaRb are - and * is the attachment site for the cationic dye moiety D
[759] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) in which L is linker (d), k is 2-10, 2-9, 2-8, 2-7, 2-6, 2-5, 2-4, 2-3, 3-10, 3-9, 3-8, 3-7, 3-6, 3-5, 3-4, 4- 10, 4-9, 4-8, 4-7, 4-6, 4-5, 5-10, 5-9, 5-8, 5-7, 5-6, 6-10, 6-9, 6-8, 6-7, 7-10, 7-9, 7-8, 8-10, 8-9, 9-10, 2, 3, 4, 5. 6, 7, 8, 9. or 10.
[760] In some variations of formula (26), (27), (28), (29), (30), (31 ), or (32) described in the paragraphs above in which L is linker (d), Ra is H and j> is H. In some variations of formula (26), (27), (28), (29), (30), (3 1 ), or (32) described in the paragraphs above in which L is linker (d), Ra is H and ¾ is CH3. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L i s linker (d), Ra and l¾> are "¾ . In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above
O
in which L is linker (d), Ra and j, are *"*· < \ In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (d), two of C aRb are x ^ .
In some variations of formula (26), (27), (28), (29), (30), (31), or (32), L is linker (e
Figure imgf000247_0001
(Θ.1 )
in which n is 0-6, ni is 1 -4, and * is the attachment site for the cationic dye moiety
[762] In some variations of formula (26), (27), (28), (29), (30), (31 ), or (32) in which L is linker (e. l), n is 0-6, 0-5, 0-4, 0-3, 0-2, 0-1, 1-6, 1 -5, 1-4, 1-3, 1-2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3- 4, 4-6, 4-5, 5-6, 0, 1 , 2, 3, 4, 5, or 6. [763] In some variations of formula (26), (27), (28), (29), (30), (31 ), or (32) described in the paragraphs above in which L is linker (e. 1), nj is 1-4, 1-3, 1-2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[764] In some variations of formula (26), (27), (28), (29), (30), (3 1 ), or (32), L is linker (f.1 ):
Figure imgf000248_0001
, in which n} is 0-5, n2 is 1-5, and * is the attachment site for the cationic dye moiety D.
[765] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) in which L is linker (f.1 ), m is 0-5, 0-4, 0-3, 0-2, 0- 1 , 1-5, 1 -4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1 , 2, 3, 4, or 5.
[766] In some variati ons of formul a (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (f.1), n2 is 1 -5, 1-4, 1-3, 1 -2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5.
[767] In some variations of formula (26), (27), (28), (29), (30), (31), or (32), L is linker (f.2):
Figure imgf000248_0002
, in which n} is 0-5, n2 is 1-5, and * is the attachment site for the cationic dye moiety D.
[768] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) in which L is linker (f.2), n;_ is 0-5, 0-4, 0-3, 0-2, 0-1, 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1, 2, 3, 4, or 5.
[769] In some variati ons of formul a (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (f.2), n? is 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5.
[770] In some variations of formula (26), (27), (28), (29), (30), (31), or (32), L is linker (g. I):
Figure imgf000249_0001
(g-1 ) in which ¾/ is 0-5, n? is 1-5, and * is the attachment site for the cationic moietv D
[771] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) in which L i s linker (g. l), m is 0-5, 0-4, 0-3, 0-2, 0-1, 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1, 2, 3, 4, or 5.
[772] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (g. l ), n2 is 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5.
[773] In some variations of formula (26), (27), (28), (29), (30), (31), or (32), L is linker (g.2):
Figure imgf000249_0002
(9-2) , in which n} is 0-5, n2 is 1-5, and * is the attachment site for the cationic dye moiety D.
[774] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) in which L is linker (g.2), m is 0-5, 0-4, 0-3, 0-2, 0-1, 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1, 2, 3, 4, or 5.
[775] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (g.2), n2 is 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5.
In some variations of formula (26), (27), (28), (29), (30), (31), or (32), L is linker (h. l):
Figure imgf000250_0001
'"· ' ' , in which m is 0-5, is 1-5, and * is the attachment site for the cationic dye moiety D.
[777] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) in which L is linker (h. l), m{ is 0-5, 0-4, 0-3, 0-2, 0- 1, 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, I, 2, 3, 4, or 5.
[778] In some variations of formula (26), (27), (28), (29), (30), (31 ), or (32) described in the paragraphs above in which L is linker (h. l), n2 is 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5.
[779] In some variations of formula (26), (27), (28), (29), (30), (31), or (32), L is linker (h.2):
Figure imgf000250_0002
in which n? is 0-5, n2 is 1 -5, and * is the attachment site for the cationic dye moiety D.
[780] In some variations of formula (26), (27), (28), (29), (30), (31 ), or (32) in which L i s linker (h.2), n, is 0-5, 0-4, 0-3, 0-2, 0-1, 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1, 2, 3, 4, or 5.
[781] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (h.2), n2 is 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1 , 2, 3, 4, or 5.
[782] In some variations of formula (26), (27), (28), (29), (30), (31), or (32), L is linker (i. l):
Figure imgf000251_0001
, in which ¾ and n2 independently are 1-5 and * is the attachment site for the cationic dye moiety D,
[783] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above, L is linker (i. l), n} is 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5.
[784] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (i . l), nj is 1-5, 1 -4, 1-3, 1 -2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1 , 2, 3, 4, or 5.
[785] In some variations of formula (26), (27), (28), (29), (30), (31), or (32), L is linker (i.2):
Figure imgf000251_0002
('2) , in which «/ and n2 independently are 1 -5 and * is the attachment site for the cationic dye moiety D.
[786] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above, L is linker (i.2), nl is 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5,
[787] In some variations of formula (26), (27), (28), (29), (30), (31 ), or (32) described in the paragraphs above in which L is linker (i.2), η{ is 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, I, 2, 3, 4, or 5.
In some variations of formula (26), (27), (28), (29), (30), (31), or (32), L is linker (j . l):
Figure imgf000252_0001
, in which n2 is 1-5 and * is the attachment site for the cationic dye moiety I).
[789] In some variations of formula (26), (27), (28), (29), (30), (31 ), or (32) in which L is linker (j . l), n2 is 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5.
] In some variations of formula (26), (27), (28), (29), (30), (31), or (32), L is linker (j .2):
Figure imgf000252_0002
, in which n2 is 1 -5 and * is the attachment site for the cationic dye moiety D.
[791] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) in which L is linker (j .2), n2 is 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5.
In some variations of formula (26), (27), (28), (29), (30), (31), or (32), L is linker (k):
Figure imgf000252_0003
' , in which and independently are 1-4, n is 1-4; ring A is aryl, heteroaryl, cycloalkyl, or heterocyclyl; (1) Rai and Rj>i independently are H or CH3 or (2) Rai and Rb! independent
Figure imgf000252_0004
or f3 ) two of CRaiRbi are (1) Ra2 and j,2 O independently are H or CH3 or (2) Ra2 and R¾2 independently are '¾ *~ or '¾ or (3) two of CRa2Rj,2 are ; and * is the attachment site for the cationic dye moiety D.
[793] In some variations of formula (26), (27), (28), (29), (30), (31 ), or (32) in which L is linker (k), h is 1-4, 1-3, 1-3, 1-2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
I] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (k), l2 i s 1 -4, 1-3, 1 -3, 1-2, 2-4, 2-3, 3-4, 1 , 2, 3, or 4.
)5] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (k), ai is H and ¾i is H. In some variations of formula (26), (27), (28), (29), (30), (31 ), or (32) described in the paragraphs above in which L is linker (k), Rai is H and ¾ι is CH3. In some variations of formula (26), (27), (28), (29), (30), (31), or
(32) described in the paragraphs above in which L is linker (k), RaJ and ^ are '¾ . In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above
O
in which L is linker (k), Rai and are '¾ *~ . In some variations of formula (26), (27), (28), (29), (30), (3 ), or (32) described in the paragraphs above in which L is linker (k), two of
CRaiRbi are
[796] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (k), Ra2 is H and ¾2 is H. In some variations of formula (26), (27), (28), (29), (30), (3 1 ), or (32) described in the paragraphs above in which L is linker (k), Ra2 is H and Rb2 is CH3. In some variations of formula (26), (27), (28), (29), (30), (31), or
(32) described in the paragraphs above in which L i s linker (k), Ra2 and ϊ¾>2 are "^- ^ . In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above
Figure imgf000253_0001
in which L is linker (k), Ra2 and I½ are '% . In some variations ot formula (26), (27), (28), (29), (30), (3 1), or (32) described in the paragraphs above in which L is linker (k), two of
CRa2R 2 are Ό'Ά
[797] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (k), ring A is (a) N or N , optionally substituted with halo or C1-C6 linear or branched alkyl,
Figure imgf000254_0001
optionally substituted with halo or C1-C6 linear or branched alkyl; or
Figure imgf000254_0002
Figure imgf000255_0001
optionally substituted with halo or C 1-C6 linear or branched alkyl.
[798] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (k), r½g A is substituted with halo. In some variations, the halo is F, Br, I, or CI.
Ϊ9] In some variations of formula (26), (27), (28), (29), (30), (31 ), or (32) described in the paragraphs above in which L is linker (k), ring A is substituted with C 1-C6 linear or branched alkyl (e.g., C 1-C6, C 1-C5, C 1-C4, C 1 -C3, C1-C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3~ C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl).
[800] In some variations of formula (26), (27), (28), (29), (30), (31), or (32), L is linker (1.
Figure imgf000255_0002
, in which lj, l2, n, oi, and o2 independently are 1-4, ring A is aryl, heteroaryl, cycloalkyl, or heterocyclyl; for each independent instance of Raj and
Rj,i, Rai and ¾ι(1) independently are H or CH3, or (2) Ra3 and RM independently are
Figure imgf000255_0003
or or (3) two of CRaiRbi ar„e * · ; for each independent instance of R¾2 and Rf,2i Ra2 and O
¾2 (1) independently are H or CH3, or (2) Ra2 and j,2 independently are "^- or '^- or (3) two of CRa2Ri,2 are ¾ ; for each independent instance of Rd and R(U; R^i and R^i ( 1 independently are H or CH , or (2) et and ¾{ independently are
Figure imgf000256_0001
or (3) two of CRciRdi are ·- , for each independent instance of Rc2 and ¾2, R«2 and R42 (1)
7 O
independently are H or CH3, or (2) ^ and d2 independently are "¾ or "¾ or (3) two of C c2 i!2 are ' <· ¾ ; and * is the attachment site for the cationic dye moiety D.
[801] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) in which L is linker (1 , 1 ), h is 1-4, 1 -3, 1-3, 1 -2, 2-4, 2-3, 3-4, 1 , 2, 3, or 4.
[802] In some variations of formula (26), (27), (28), (29), (30), (31 ), or (32) described in the paragraphs above in which L is linker (1.1), h is 1-4, 1-3, 1-3, 1 -2, 2-4, 2-3, 3-4, 1 , 2, 3, or 4.
[803] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (1. 1), Oi is 1-4, 1 -3, 1-3, 1 -2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[804] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (1.1), 2 is 1-4, 1 -3, 1-3, 1 -2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[805] In some variations of formula (26), (27), (28), (29), (30), (: 1), or (32) described in the paragraphs above in which L is linker (1.1), Rai is H and Rbi i s H. n some variations of formula (26), (27), (28), (29), (30), (3 1), or (32) described in the paragraph; s above in which L is linker
L I ), Rai is H and RM is CH3. In some variations of formula (26), (27), (28), (29), (30), (31), or
(32) described in the paragraphs above in which L is linker (1.1), RaS and R¾i are . In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above
p
in which L is linker (1.1), Rai ^nd R¾i are "¾ ^\ In some variations ot formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (1.1), two of
λ
C aiRj)i are ' [806] In some variations of formula (26), (27), (28), (29), (30), (31 ), or (32) described in the paragraphs above in which L is linker (1.1), is H and Rb2 is H. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (1.1), Ra2 is H and ¾2 is C¾. In some variations of formula (26), (27), (28), (29), (30), (31), or
(32) described in the paragraphs above in which L is linker (1.1), Ra2 and ¾2 are ^ . In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above
O
in which L is linker (1. 1), Ra2 and j,2 are - . In some variations of formula (26), (27), (28),
) described in the paragraphs above in which L is linker (1.1), two of
Figure imgf000257_0001
[807] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (1.1), Rci and ^i are both H. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (1.1), R^ is H and R<u is C¾. I In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (1.1), Rci and Ι¾ι are both C¾. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (1.1), R-i and R<n are
Figure imgf000257_0002
. In some variations of formula
(26), (27), (28), (29), (30), (31 ), or (32) described in the paragraphs above in which L is linker
O
(1.1), Rci and di are In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (1.1), two of CRciR<u are ^ ^i
[808] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (1.1), and d? are both H. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (1.1), ^ is H and Rd2 is CH3. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (1.1), c2 and 42 are both CH3. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (1.1), Rc2 and R<j2 are ^ . In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker W
O
(1.1), Rt2 and ¾ are "*· ? in some variations of fomusla (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (1.1), two of CRc2¾2 are
In some variations of formula (26), (27), (28), (29), (30), (31 ), or (32) described in the paragraphs above in which L is linker (1.1 ), ring A is
optionally substituted
Figure imgf000258_0001
with halo or C1-C6 linear or branched alkyl;
Figure imgf000258_0002
optionally substituted with halo or C I -Co linear or branched alkyl; or
Figure imgf000258_0003
Figure imgf000259_0001
optionally substituted with halo or C 1-C6 linear or branched alkyl.
[810] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (1. i), ring A is substituted with halo. In some variations, the halo is F, Br, I, or CI.
[811] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (1.1), ring A is substituted with C1 -C6 linear or branched alkyl (e.g., C1-C6, C 1-C5, C1-C4, C1-C3, C1-C2, C I , C2-C6, C2-C5, C2-C4, C2-C3, C2, C3- C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl).
[812] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (1.1), n is 1-4, 1 -3, 1-3, 1 -2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[813] In some variations of formula (26), (27), (28), (29), (30), (31), or (32), L is linker (1.2):
Figure imgf000260_0001
(!.2) , in which U, l2, n, and i¾ independently are 1-4, ring A is aryl, heteroaryl, cycloalkvl, or heterocvclyl; for each independent instance of Rai and and Rbi(l) independently are H or CH3, or (2) ai and Rbi independently are "¾
0
"¾ or (3) two of ½IKM are for each independent instance of Ra2 and Rb2, a2 and
Rb2 (1 ) independently are H or CH3, or (2) Ra2 and i>2
Figure imgf000260_0002
two of CRa2 b2 are ""^ ; for each independent instance of Rcj and R<U j ^ and Rdi (1) ndependently are H or CH3, or (2) Rcl and
Figure imgf000260_0003
CRciRai are >SK for each independent instance of ¾2 and ^, «2 and ^ (1 ) independently are H or CH , or (2) c2 and ¾2 independently are
Figure imgf000260_0004
or (3) two CRc2Rd2 are " ·· , and * is the attachment site for the cationic dye moiety D.
[814] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) in which L is linker (1.2), h is 1-4, 1-3, 1 -3, 1-2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[815] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (1.2), l2 is 1-4, 1-3, 1-3, 1-2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[816] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (1.2), oi is 1 -4, 1-3, 1 -3, 1-2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[817] In some variations of formula (26), (27), (28), (29), (30), (31 ), or (32) described in the paragraphs above in which L is linker (1.2), o2 is 1-4, 1-3, 1 -3, 1-2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[818] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (1.2), Ra! is H and Rt>i is H. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker ,2), Rai is H and RM is CH3. In some variations of formula (26), (27), (28), (29), (30), (31), or
(32) described in the paragraphs above in which L is linker (1.2), RaS and R¾i are
Figure imgf000261_0001
. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above p
in which L is linker (1.2), Rai and ¾ι are "¾ * " . In some variations ot formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (1.2), two of
C aiR-M are ^ ^ .
[819] In some variations of formula (26), (27), (28), (29), (30), (31 ), or (32) described in the paragraphs above in which L is linker (1.2), ^ is H and I¾2 is H. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (1.2), Ra2 is H and Rb2 is C¾. In some variations of formula (26), (27), (28), (29), (30), (31), or
(32) described in the paragraphs above in which L is linker (1.2), and are
Figure imgf000261_0002
. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above
O
in which L is linker (1.2), Ra2 and j,2 are ^ . In some variations of formula (26), (27), (28),
2) described in the paragraphs above in which L is linker (1.2), two of
Figure imgf000261_0003
[820] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (1.2), ci and ^i are both H. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (1.2), Rti is H and RJI is CH . In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (1 ,2), ci and Ι¾ι are both C¾. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (1.2), R^ and <n are . In some variations of formula
(26), (27), (28), (29), (30), (31 ), or (32) described in the paragraphs above in which L is linker
O
(1.2), ci and RlU are ^ * In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (1.2), two of C ci di are ""^ [821] In some variations of formula (26), (27), (28), (29), (30), (31 ), or (32) described in the paragraphs above in which L is linker (1.2), ¾~2 and R<j2 are both H. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (1.2), is H and I½ is C¾. In some variations of formula (26), (27), (28), (29), (30), (3 1), or (32) described in the paragraphs above in which L is linker (1.2), and R,¾2 are both C¾. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (1.2), Re2 and ¾2 are . In some variations of formula
(26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker
O
(1.2), Rc2 and ¾2 are "^- ^ , In some variations of formula (26), (27), (28), (29), (30), (31), or
'32) described in the paragraphs above in which L is linker (1.2), two of CRc2Rd2 are
Figure imgf000262_0001
[822] In some variati ons of formul a (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (1.2), ring A is
Figure imgf000262_0002
optionally substituted with halo or C1-C6 linear or branched alkvl
Figure imgf000262_0003
optionally substituted with halo or C1-C6 linear or branched aikyi; or
Figure imgf000262_0004
Figure imgf000263_0001
optionally substituted with halo or C1 -C6 linear or branched alkyl.
[823] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (1.2), ring A is substituted with halo. In some variations, the halo is F, Br, I, or CI .
[824] In some variations of formula (26), (27), (28), (29), (30), (31 ), or (32) described in the paragraphs above in which L is linker (1.2), ring A is substituted with C1-C6 linear or branched alkyl (e.g., C1-C6, C1-C5, C1-C4, C1-C3, C1-C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3~ C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). [825] In some variations of formula (26), (27), (28), (29), (30), (31 ), or (32) described in the paragraphs above in which L is linker (1.2), n is 1-4, 1-3, 1-3, 1-2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[826] In some variations of formula (26), (27), (28), (29), (30), (3 1 ), or (32), L is linker (m.1):
Figure imgf000264_0001
, in which n is 0-6, ¾/ is 1-4, and * is the attachment site for the cationic dye moiety
[827] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) in which L is linker (m. l), n i s 0-6, 0-5, 0-4, 0-3, 0-2, 0-1, 1-6, 1 -5, 1-4, 1 -3, 1-2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 4, 4-6, 4-5, 5-6, 0, 1 , 2, 3, 4, 5, or 6.
[828] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (m. l), nj is 1-4, 1 -3, 1-2, 2-4, 2-3, 3-4, I, 2, 3, or 4.
[829] In some variati ons of formul a (26), (27), (28), (29), (30), (31), or (32), L is linker (n, 1 ):
in which n2 is 1-5 and * is the attachment site for the cationic dye
Figure imgf000264_0002
[830] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) in which L is linker (n. I), n2 is 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5.
In some variations of formula (26), (27), (28), (29), (30), (31), or (32), L is linker (n.2)
Figure imgf000265_0001
(n.2) , in which n2 is 1 -5 and * is the attachment site for the catiomc dye moietv D.
In some variations of formula (26), (27), (28), (29), (30), (31), or (32) in which L • (n.2), n2 is 1-5, 1-4, 1-3, 1 -2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5.
[833] In some variati ons of formula (26), (27), (28), (29), (30), (31), or (32), L is linker (o):
Figure imgf000265_0002
'0' , in which in which ¾ is 0-5, n2 is 1 -5, n3 is 0-5, and * is the attachment site for the cationic dye moiety D,
[834] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) in which L is linker (o), »7 is 0-5, 0-4, 0-3, 0-2, 0-1, 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1, 2, 3, 4, or 5.
[835] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (o), n2 is 1 -5, 1-4, 1 -3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5.
[836] In some variations of formula (26), (27), (28), (29), (30), (3 1 ), or (32) described in the paragraphs above in which L is linker (o), is 0-5, 0-4, 0-3, 0-2, 0-1, 1-5, 1-4, 1-3, 1-2, 2-5, 2- 4, 2-3, 3-5, 3-4, 4-5, 0, 1, 2, 3, 4, or 5.
[837] In some variations of formula (26), (27), (28), (29), (30), (31), or (32), L is linker (p):
Figure imgf000266_0001
(Ρ) , in which nj is 0-5, i2 is 1-5, n3 is 0-5, and * is the attachment site for the cationic dye moiety D,
[838] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described above in which L is linker (p), m is 0-5, 0-4, 0-3, 0-2, 0-1, 1 -5, 1-4, 1 -3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1, 2, 3, 4, or 5.
[839] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described above in which L is linker (p), n2 is 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1 , 2, 3, 4, or 5.
[840] In some variations of formula (26), (27), (28), (29), (30), (31 ), or (32) described above in which L is linker (p), n3 is 0-5, 0-4, 0-3, 0-2, 0-1, 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1, 2, 3, 4, or 5.
[841] In some variations of formula (26), (27), (28), (29), (30), (31), or (32), L is linker (q):
Figure imgf000266_0002
(q) , in which n.4 is 0-5, «2 is 1-5, and * is the attachment site for the cationic dye moiety D.
[842] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) in which L is linker (o), n4 is 0-5, 0-4, 0-3, 0-2, 0-1, 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1, 2, 3, 4, or 5,
[843] In some variations of formula (26), (27), (28), (29), (30), (31 ), or (32) described above in which L is linker (q), n2 is 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5.
[844] In some variations of formula (26), (27), (28), (29), (30), (31), or (32), L is linker (r):
Figure imgf000267_0001
(r) , in which n} is 0-5, n2 is 1-5, n3 is 0-5, and * is the attachment site for the cationic dye moiety D,
[845] In some of variations of formula (26), (27), (28), (29), (30), (31), or (32) in which L is linker (r), n:i is 0-5, 0-4, 0-3, 0-2, 0-1, 1-5, 1-4, 1-3, 1 -2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1, 2, 3, 4, or 5,
[846] In some of variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which L is linker (r), n2 is 1 -5, 1-4, 1 -3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5.
[847] In some of variations of formula (26), (27), (28), (29), (30), (31), or (32) in which L is linker (r), n3 is 0-5, 0-4, 0-3, 0-2, 0-1, 1-5, 1-4, 1-3, 1 -2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1, 2, 3, 4, or 5.
[848] In some variations of formula (26), (27), (28), (29), (30), (31), or (32), L is linker (s):
Figure imgf000267_0002
(s) , in which rti is 0-5, n2 is 1-5, n3 is 0-5, and * is the attachment site for the cationic dye moiety D.
[849] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described above in which L is linker (s), m is 0-5, 0-4, 0-3, 0-2, 0-1, 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1, 2, 3, 4, or 5.
[850] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described above in which L is linker (s), n2 is 1-5, 1-4, 1 -3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5. [851] In some variations of formula (26), (27), (28), (29), (30), (31 ), or (32) described above in which L is linker (s), n3 is 0-5, 0-4, 0-3, 0-2, 0-1, 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0,
1, 2, 3, 4, or 5.
[852] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described above, L is absent.
[853] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above, ¾x is 0-5, 0-4, 0-3, 0-2, 0-1, 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, I,
2, 3, 4, or 5.
[854] In some variations of formula (26), (27), (28), (29), (30), (31 ), or (32) described in the paragraphs above, ny is 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5.
[855] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above, I) is selected from the group consisting of safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue.
[856] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which n2 is greater than 1, each D is represented consecutively from left to right as Dl, D2, D3, D4, and D5, as appropriate for the value of ny.
[857] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which ny is 2, Dl and D2 are the same cationic dye moiety. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) in which ny is 2, Dl and D2 are different cationic dye moieties. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) in which ny is 2, Dl and D2 independently are selected from the group consisting of safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue.
[858] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which ny is 3, Dl, D2, and D3 are the same cationic dye moiety. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) in which ny is 3, Dl, D2, and D3 are different cationic dye moieties. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) in which ny is 3, Dl and D2 and the same cationic dye moiety and D3 is a different cationic dye moiety. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) in which ny is 3, Dl and D3 and the same cationic dye moiety and D2 is a different cationic dye moiety. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) in which ny is 3, D2 and D3 and the same cationic dye moiety and 1)1 is a different cationic dye moiety. n some variations of formula (26), (27), (28), (29), (30), (31), or (32) in which ny is 3, Dl, D2, and D3 independently are selected from the group consisting of safranin-Q, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue.
[859] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which ny is 4, Dl, D2, D3, and D4 are the same cationic dye moiety. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) in which my is 4, Dl, D2, D3. and D4 are different cationic dy e moieties. In some variations of formula (26), (27), (28), (29), (30), (31), or (32), Dl is a first cationic dye moiety and each of D2, D3, and D4 is the same second cationic dye moiety, wherein the first and second cationic dye moieties are different. In some variations of formula (26), (27), (28), (29), (30), (31), or (32), D2 is a first cationic dye moiety, and each of Dl, D3, and D4 is a second cationic dye moiety, wherein the first and second cationic dye moieties are different. In some variations of formula (26), (27), (28), (29),
(30) , (31), or (32), D3 is a first cationic dye moiety, and each of Dl, D2, and D4 is a second cationic dye moiety, wherein the first and second cationic dye moieties are different. In some variations of formula (26), (27), (28), (29), (30), (31), or (32), D4 is a first cationic dye moi ety, and each of Dl, D2, and D3 is a second cationic dye moiety, wherein the first and second cationic dye moieties are different. In some variations of formula (26), (27), (28), (29), (30),
(31) , or (32), each of Dl and D2 is the same first cationic dye moiety, and each of D3 and D4 is the same second cationic dye moiety, wherein the first and second cationic dye moieties are different. In some variations of formula (26), (27), (28), (29), (30), (31), or (32), each of Dl and D2 is the same first cationic dye moiety, D3 is a second cationic dye moiety, and D4 is a third cationic dye moiety, wherein the first, second, and third cationic dye moieties are different. In some variations of formula (26), (27), (28), (29), (30), (31), or (32), each of Dl and D3 is the same first cationic dye moiety, and each of D2 and D4 is the same second cationic dye moiety, wherein the first and second cationic dye moieties are different. In some variations of formula (26), (27), (28), (29), (30), (31), or (32), each of Dl and D3 is the same first cationic dye moiety, D2 is a second cationic dye moiety, and D4 is a third cationic dye moiety, wherein the first, second, and third cationic dye moieties are different. In some variations of formula (26), (27), (28), (29), (30), (31), or (32), each of Dl and D4 is the same first cationic dye moiety, and each of D2 and D3 is the same second cationic dye moiety, wherein the first and second cationic dye moieties are different. In some variations of formula (26), (27), (28), (29), (30), (31), or (32), each of Dl and D4 is the same first cationic dye moiety, D2 is a different second cationic dye moiety, and D3 is a different third cationic dye moiety, wherein the first, second, and third cationic dye moieties are different. In some variations of formula (26), (27), (28), (29), (30), (31), or (32), each of D2 and D3 is the same first cationic dye moiety, and each of Dl and D4 is the same second cationic dye moiety, wherein the first and second cationic dye moieties are different. In some variations of formula (26), (27), (28), (29), (30), (31), or (32), (26), (27), (28),
(29) , (30), (30), or (32) in which ny is 4, Dl, D2, D3, and D4 independently are selected from the group consisting of safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acrifiavine, and methylene blue.
[860] In some variations of formula (26), (27), (28), (29), (30), (31 ), or (32) described in the paragraphs above in which ny is 5, Dl, D2, D3, D4, and D5 are different cationic dye moieties. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which ny is 5, Dl, D2, D3, D4, and D5 are the same cationic dye moiety. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which ny is 5, Dl and D2 are a first cationic dye moiety, D3 is a second cationic dye moiety, D4 is a third cationic dye moiety, and D5 is a fourth cationic dye moiety, wherein the first, second, third, and fourth cationic dye moieties are different. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which ny is 5, Dl and D2 are a first cationic dye moiety, D3 is a second cationic dye moiety, and D4 and D5 each are a third cationic dye moiety, wherein the first, second, and third cationic dye moieties are different. In some variations of formula (26), (27), (28), (29), (30), (3 ), or (32) described in the paragraphs above in which ny is 5, Dl and D2 are a first cationic dye moiety, D3 and D4 are a second cationic dye moiety, and D5 is a third cationic dye moiety, wherein the first, second, and third cationic dye moieties are different. In some variations of formula (26), (27), (28), (29),
(30) , (31), or (32) described in the paragraphs above in which ny is 5, Dl and D2 are a first cationic dye moiety, D3 and D5 are a second cationic dye moiety, and D4 is a third cationic dye moiety, wherein the first, second, and third cationic dye moieties are different.
[861] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which ny is 5, Dl and D3 are a first cationic dye moiety, D2 is a second cationic dye moiety, D4 is a third cationic dye moiety, and D5 is a fourth cationic dye moiety, wherein the first, second, third, and fourth cationic dye moieties are different. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which ny is 5, Dl and D3 are a first cationic dye moiety, D5 is a second cationic dye moiety, and D2 and D4 each are a third cationic dye moiety, wherein the first, second, and third cationic dye moieties are different. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which ny is 5, Dl and D3 are a first cationic dye moiety, D2 and D5 are a second cationic dye moiety, and 1)4 is a third cationic dye moiety, wherein the first, second, and third cationic dye moieties are different. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which ny is 5, Dl and D3 are a first cationic dye moiety, D4 and D5 are a second cationic dye moiety, and D3 is a third cationic dye moiety, wherein the first, second, and third cationic dye moieties are different.
[862] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which ny is 5, Dl and D4 are a first cationic dye moiety, D2 is a second cationic dye moiety, D3 is a third cationic dye moiety, and D5 is a fourth cationic dye moiety, wherein the first, second, third, and fourth cationic dye moieties are different. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which ny is 5, Dl and 1)4 are a first cationic dye moiety, D3 is a second cationic dye moiety, and 1)2 and D5 each are a third cationic dye moiety, wherein the first, second, and third cationic dye moieties are different. In some vari ations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which ny is 5, Dl and D4 are a first cationic dye moiety, D2 and D3 are a second cationic dye moiety, and D5 is a third cationic dye moiety, wherein the first, second, and third cationic dye moieties are different. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which ny is 5, Dl and D4 are a first cationic dye moiety, D3 and D5 are a second cationic dye moiety, and D2 is a third cationic dye moiety, wherein the first, second, and third cationic dye moieties are different.
[863] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which ny is 5, Dl and D5 are a first cationic dye moiety, D2 is a second cationic dye moiety, D3 is a third cationic dye moiety, and D4 is a fourth cationic dye moiety, wherein the first, second, third, and fourth cationic dye moieties are different. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which ny is 5, Dl and D5 are a first cationic dye moiety, D4 is a second cationic dye moiety, and D2 and D3 each are a third cationic dye moiety, wherein the first, second, and third cationic dye moieties are different. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which ny is 5, Dl and D5 are a first cationic dye moiety, D3 and D4 are a second cationic dye moiety, and D2 is a third cationic dye moiety, wherein the first second, and third cationic dye moieties are different. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which ny is 5, Dl and D5 are a first cationic dye moiety, D2 and D4 are a second cationic dye moiety, and D3 is a third cationic dye moiety, wherein the first, second, and third cationic dye moieties are different. [864] In some variations of formula (26), (27), (28), (29), (30), (31 ), or (32) described in the paragraphs above in which ny is 5, D2 and D3 are a first cationic dye moiety, Dl is a second cationic dye moiety, D4 is a third cationic dye moiety, and D5 is a fourth cationic dye moiety, wherein the first, second, third, and fourth cationic dye moieties are different. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which ny is 5, D2 and D3 are a first cationic dye moiety, Dl is a second cationic dye moiety, and D4 and D3 each are a third cationic dye moiety, wherein the first, second, and third cationic dye moieties are different.
[865] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which ny is 5, D2 and D4 are a first cationic dye moiety, Dl is a second cationic dye moiety, 1)3 is a third cationic dye moiety, and D5 is a fourth cationic dye moiety, wherein the first, second, third, and fourth cationic dye moieties are different. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which ny is 5, D2 and D4 are a first cationic dye moiety, Dl is a second cationic dye moiety, and D3 and D5 each are a third cationic dye moiety, wherein the first, second, and third cationic dye moieties are different.
[866] In some variations of formula (26), (27), (28), (29), (30), (3 1 ), or (32) described in the paragraphs above in which ny is 5, D2 and D5 are a first cationic dye moiety, Dl is a second cationic dye moiety, D3 is a third cationic dye moiety, and D4 is a fourth cationic dye moiety, wherein the first, second, third, and fourth cationic dye moieties are different. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which ny is 5, D2 and D5 are a first cationic dye moiety, Dl is a second cationic dye moiety, and D3 and D4 each are a third cationic dye moiety, wherein the first, second, and third cationic dye moieties are different.
[867] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which ny is 5, D3 and D4 are a first cationic dye moiety, Dl is a second cationic dye moiety, D2 is a third cationic dye moiety, and D5 is a fourth cationic dye moiety, wherein the first, second, third, and fourth cationic dye moieties are different.
[868] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which ny is 5, D4 and D5 are a first cationic dye moiety, Dl is a second cationic dye moiety, D2 is a third cationic dye moiety, and D3 is a fourth cationic dye moiety, wherein the first, second, third, and fourth cationic dye moieties are different. [869] In some variations of formula (26), (27), (28), (29), (30), (31 ), or (32) described in the paragraphs above in which ny is 5, Dl, D2, and D3 are a first cationic dye moietv, D4 is a second cationic dye moiety, and D5 is a third cationic dye moiety, wherein the first, second, and third catiomc dye moieties are different. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which ny is 5, Dl, D2, and D3 are a first cationic dye moiety, and D4 and D5 are a second cationic dye moiety, wherein the first and second cationic dye moieties are different.
[870] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which ny is 5, D2, D3, and D4 are a first cationic dye moiety, Dl is a second cationic dye moiety, and D5 is a third cationic dye moiety, wherein the first, second, and third cationic dye moieties are different. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which ny is 5, D2, D3, and D4 are a first cationic dye moiety, and Dl and D5 are a second cationic dye moiety, wherein the first and second cationic dye moieties are different.
[871] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which ny is 5, D3, D4, and D5 are a first cationic dye moiety, Dl is a second cationic dye moiety, and D2 is a third cationic dye moiety, wherein the first, second, and third catiomc dye moieties are different. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which ny is 5, D3, D4, and D5 are a first cationic dye moiety, and Dl and D2 are a second cationic dye moiety, wherein the first and second cationic dye moieties are different.
[872] In some variati ons of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which ny is 5, Dl, D4, and D5 are a first cationic dye moiety, D2 is a second cationic dye moiety, and D3 is a third cationic dye moiety, wherein the first, second, and third catiomc dye moieties are different. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which ny is 5, Dl, D4, and D5 are a first cationic dye moiety, and D2 and D3 are a second cationic dye moiety, wherein the first and second cationic dye moieties are different.
[873] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which ny is 5, Dl, D2, and D5 are a first cationic dye moiety, D3 is a second cationic dye moiety, and D4 is a third cationic dye moiety, wherein the first, second, and third cationic dye moieties are different. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which ny is 5, Dl, D2, and D5 are a first cationic dye moiety, and D3 and D4 are a second cationic dye moiety, wherein the first and second catiomc dye moieties are different.
[874] In some variations of formula (26), (27), (28), (29), (30), (3 1 ), or (32) described in the paragraphs above in which ny is 5, Dl is a first catiomc dye moiety, and each of D2, D3, D4, and D5 is a second cationic dye moiety, wherein the first and second cationic dye moieties are different. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which ny is 5, D2 is a first cationic dye moiety, and each of Dl, D3, D4, and D5 is a second cationic dye moiety, wherein the first and second cationic dye moieties are different. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which ny is 5, D3 is a first catiomc dye moiety, and each of Dl, D2, D4, and D5 is a second cationic dye moiety, wherein the first ami second cationic dye moieties are different. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which ny is 5, D4 is a first catiomc dye moiety, and each of Dl, D2, D3, and D5 is a second cationic dye moiety, wherein the first and second cationic dye moieties are different. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which ny is 5, D5 is a first cationic dye moiety, and each of Dl, D2, D3, and D4 is a second cationic dye moiety, wherein the first and second cationic dye moieties are different.
[875] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above in which ny is 5, Dl, D2, D3, D4, and D5 independently are selected from the group consisting of safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue.
[876] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above, Dl is safranin-O. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above, D2 is safranin-O. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above, D3 is safranin-O. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above, D4 is safranin-O. In some variations of formula (26), (27), (28), (29), (30), (31 ), or (32) described in the paragraphs above, Dl and D2 are safranin-O. In some variations of formula (26), (27), (28), (29), (30), (31 ), or (32) described in the paragraphs above, Dl and D3 are safranin-O. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above, Dl and D4 are safranin-O. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above, D2 and D3 are safranin-O. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above, D2 and D4 are safranin-O. In some variations of formula (26), (27), (28), (29), (30), (3 1), or (32) described in the paragraphs above, D3 and D4 are safranin-O. In some variations of formula (26), (27), (28), (29), (30), (31 ), or (32) described in the paragraphs above, Dl, D2, and D3 are safranin-O. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraphs above, Dl, D2, and D4 are safranin-O. In some variations of formula (26), (27),
(28) , (29), (30), (3 1), or (32) described in the paragraphs above, Dl, D3, and D4 are safranin-O. In some variations of formula (26), (27), (28), (29), (30), (3 1 ), or (32) described in the paragraphs above, D2, D3, and D4 are safranin-O. In some variations of formula (26), (27), (28),
(29) , (30), (3 1 ), or (32) described in the paragraphs above, Dl, D2, D3, and D4 are safranin-O.
[877] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraph above, the pendant phenyl ring ofDl is unsubstituted. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraph above, the pendant phenyl ring ofDl is substituted with 1-3 (e.g., 1 -3, 1-2, 1, 2, or 3) electron-donating or electron- withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring ofDl is substituted, the substituents are selected independently from— -NH2, --NH , --NR2, Oi l. 0\ NHCOCH3, --NHCOR,—OCH3, — OR,— C2H5,— R, and— C6H5, wherein R is C 1-C6 linear or branched alkyl (e.g., C 1-C6, C l- C5, C1-C4, C1 -C3, C1 -C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— \0 \ R : \ halo (e.g., F, Br, CI, I), trihalide (e.g.. ---CF3, CTk—CBr3, --CI3),— CN,— SO3II,— COOH,— COOR,— CI 10, and—COR, wherein R is C 1-C6 linear or branched alkyl (e.g., C 1-C6, C1-C5, C 1-C4, C 1-C3, C1-C2, C I , C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl).
[878] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the two paragraphs above, the pendant phenyl ring of D2 is unsubstituted. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraph above, the pendant phenyl ring of D2 is substituted with 1-3 (e.g., 1-3, 1-2, 1, 2, or 3) electron-donating or electron- withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— -NH2, --NHR,— NR2, Oi l. 0\— NHCOCH3, --NHCOR, --OCH3, — OR,— C2H5,— , and— C&¾, wherein R is C 1-C6 linear or branched alkyl (e.g., C1-C6, C l- C5, C 1-C4, C 1 -C3, C 1-C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from — N02— NR3 +, halo (e.g., F, Br, CI, I), trihalide (e.g.,— CF3,— CC13,— CBr3,— CI3),— CN, — SO3H,— COOH,— COOR,— CHO, and— COR, wherein R is C 1-C6 linear or branched alkyl (e.g., C 1-C6, C 1 -C5, C 1-C4, C 1 -C3, C 1-C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3- C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl).
[879] In some variati ons of formul a (26), (27), (28), (29), (30), (31), or (32) described in the three paragraphs above, the pendant phenyl ring of 1)3 is unsubstituted. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraph above, the pendant phenyl ring of 1)3 is substituted with 1-3 (e.g., 1-3, 1 -2, 1, 2, or 3) electron-donating or electron- withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of D3 is substituted, the substituents are selected independently from— -NH2, --NHR,— R2,— OH, 0\— NHCOCH3, --NHCOR,—OCH3, — OR,— C2 I5,— R, and— CeHj, wherein R is C 1-C6 linear or branched alkyl (e.g., C1-C6, C l - C5, C1-C4, C1 -C3, C1-C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of 1)3 is substituted, the substituents are selected independently from — N02— R3 +, halo (e.g., F, Br, CI, I), trihalide (e.g.,— CF3,— CCI3,— CBr3,— CI3),— CN, — SO3H,— COOH,— COOR,— CHO, and— COR, wherein R is C 1-C6 linear or branched alkyl (e.g., C 1-C6, C 1-C5, C 1-C4, C 1-C3, C 1-C2, CI, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3- C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl).
[880] In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the three paragraphs above, the pendant phenyl ring of D4 is unsubstituted. In some variations of formula (26), (27), (28), (29), (30), (31), or (32) described in the paragraph above, the pendant phenyl ring of D4 is substituted with 1-3 (e.g., 1-3, 1 -2, 1, 2, or 3) electron-donating or electron- withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of D4 is substituted, the substituents are selected independently from— -NH2, --NHR,— 'NR2,— OH, 0\ --NHCOCH3, --NHCOR,—OCH3, — OR,— C2H5,— , and— C6H5, wherein R is C 1-C6 linear or branched alkyl (e.g., C 1-C6, C l- C5, C1-C4, C1 -C3, C1 -C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of 1)4 is substituted, the substituents are selected independently from — O2,— R3 +, halo (e.g., F, Br, CI, I), trihalide (e.g., --CF3, --CCI3, ---CBr3, --CI3),— CN, — SO3H,—COOH,— COOR,—CHO, and—COR, wherein R is C 1-C6 linear or branched alkyl (e.g., C 1 -C6, C 1 -C5, C1 -C4, C 1 -C3, C 1 -C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3- C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl).
In some variations, cationic dye multimers are linear, as illustrated by formula (33):
Figure imgf000277_0001
(33) wherein each of Dl, D2, D3, and D4 is a cationic dye moiety and one or more of LI, L2, L3, and L4 are absent or each of Li, L2, L3, and L4 i s a linker independently selected from linker (a. l ), linker (a.2), linker (b. l), linker (c. l ), linker (c.2), linker (d), linker (e. l), linker (f. l ), linker (f.2), linker (g. l), linker (g.2), linker (h. l ), linker (h.2), linker (i . l), linker (i.2), linker (j . 1), linker (j .2), linker (k), linker (1.1), linker (1.2), is linker (m. l), linker (n. l ), linker (n.2), linker (o), linker (p), linker (q), linker (r), and linker (s), described above.
[882] In some variations of formula (33), each of Dl, D2, D3, and D4 is a different cationic dye moiety. In some variations of formula (33), each of Dl, D2, D3, and D4 is the same cationic dye moiety. In some variations of formula (33), 1)1 i s a first cationic dye moiety and each of 1)2, D3, and D4 is the same second cationic dye moiety, wherein the first and second cationic dye moieties are different. In some variations of formula (33), D2 is a first cationic dye moiety, and each of Dl, D3, and D4 is a second cationic dye moiety, wherein the first and second cationic dye moieties are different. In some variations of formuia (33), D3 is a first cationic dye moiety, and each of Dl, D2, and D4 is a second cationic dye moiety, wherein the first and second cationic dye moieties are different. In some variations of formuia (33), D4 is a first cationic dye moiety, and each of Dl, D2, and D3 is a second cationic dye moiety, wherein the first and second cationic dye moieties are different. In some variations of formula (33), each of Dl and D2 is the same first cationic dye moiety, and each of D3 and 1)4 is the same second cationic dye moiety, wherein the first and second cationic dye moieties are different. In some variations of formula (33), each of Dl and D2 is the same first cationic dye moiety, D3 is a second cationic dye moiety, and D4 is a third cationic dye moiety, wherein the first, second, and third cationic dye moieties are different. In some variations of formula (33), each of Dl and D3 is the same first cationic dye moiety, and each of D2 and D4 is the same second cationic dye moiety, wherein the first and second cationic dye moieties are different. In some variations of formula (33), each of Dl and D3 is the same first catiomc dye moiety, D2 is a second cationic dye moiety, and D4 is a third cationic dye moiety, wherein the first, second, and third cationic dye moieties are different. In some variations of formula (33), each of Dl and D4 is the same first cationic dye moiety, and each of D2 and D3 is the same second cationic dye moiety, wherein the first and second cationic dye moieties are different. In some variations of formula (33), each of Dl and D4 is the same first cationic dye moiety, D2 is a different second cationic dye moiety, and D3 is a different third cationic dye moiety, wherein the first, second, and third cationic dye moieties are different. In some variations of formula (33), each of D2 and D3 is the same first cationic dye moiety, and each of Dl and D4 is the same second cationic dye moiety, wherein the first and second cationic dye moieties are different,
[883] In some variations of formula (33) described in the paragraphs above, each of Dl, D2, D3, and D4 is independently are selected from the group consisting of safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue.
[884] In some variations of formula (33) described in the paragraphs above, at least one of LI, L2, L3, and L4 is linker (a. l):
Figure imgf000278_0001
(a,1 ) , in which n is 1-6, «/ is 1-4, and * is the attachment site for the cationic dye moiety D.
[885] In some variations of formula (33) in which at least one of LI, L2, L3, and L4 is linker (a. l), n is 1-6, 1-5, 1 -4, 1-3, 1-2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, 5-6, 1, 2, 3, 4, 5, or 6.
[886] In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (a. l), is 1-4, 1-3, 1 -2, 2-4, 2-3, 3-4, 1, 2, 3, or 4. [887] In some variations of formula (33) described in the paragraphs above, LI is linker (a. l). In some variations of formula (33) described in the paragraphs above, L2 is linker (a. l). In some variations of formula (33) described in the paragraphs above, L3 is linker (a. l). In some variations of formula (33) described in the paragraphs above, L4 is linker (a. l). In some variations of formula (33) described in the paragraphs above, LI and L2 are linker (a. l). In some variations of formula (33) described in the paragraphs above, LI and L3 are linker (a. l). In some variations of formula (33) described in the paragraphs above, LI and L4 are linker (a. l). In some variations of formula (33) described in the paragraphs above, L2 and L3 are linker (a. l ). In some variations of formula (33) described in the paragraphs above, L2 and L4 are linker (a. l). In some variations of formula (33) described in the paragraphs above, L3 and L4 are linker (a. l ). In some variations of formula (33) described in the paragraphs above, LI, L2, and L3 are linker (a. l). In some variations of formula (33) described in the paragraphs above, LI, L2, and L4 are linker (a. l). In some variations of formula (33) described in the paragraphs above, LI, L3, and L4 are linker (a. l). In some variations of formula (33) described in the paragraphs above, L2, L3, and L4 are linker (a. l). In some variations of formula (33) described in the paragraphs above, LI, L2, L3, and L4 are linker (a. l).
[888] In some variations of formula (33) described in the paragraphs above, at least one of LI, L2, L3, and L4 is linker (a.2):
Figure imgf000279_0001
(a.2) , in which n is 1-6, ns is 1-4, and * is the attachment site for the cationic dye moiety D.
[889] In some variations of formula (33) in which at least one of LI, L2, L3, and L4 is linker (a.2), n is 1-6, 1-5, 1-4, 1-3, 1-2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, 5-6, 1, 2, 3, 4, 5, or 6.
[890] In some variations of formula (33) described in the paragraphs above in which at least one of LI, 12, 1,3, and L4 is linker (a.2), m is 1-4, 1-3, 1 -2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[891] In some variati ons of formula (33) described in the paragraphs above, LI i s linker (a.2). In some variations of formula (33) described in the paragraphs above, L2 is linker (a.2). In some vari ations of formula (33) described in the paragraphs above, L3 is linker (a.2). In some variations of formula (33) described in the paragraphs above, L4 is linker (a.2). In some variations of formula (33) described in the paragraphs above, LI and L2 are linker (a.2). In some variations of formula (33) described in the paragraphs above, LI and L3 are linker (a, 2). In some variations of formula (33) described in the paragraphs above, LI and L4 are linker (a.2). In some variations of formula (33) described in the paragraphs above, L2 and L3 are linker (a.2). In some variations of formula (33) described in the paragraphs above, L2 and L4 are linker (a.2). In some variations of formula (33) described in the paragraphs above, L3 and L4 are linker (a.2). In some variations of formula (33) described in the paragraphs above, LI, L2, and L3 are linker (a, 2). In some variations of formula (33) described in the paragraphs above, LI, L2, and L4 are linker (a.2). In some variations of formula (33) described in the paragraphs above, LI, L3, and L4 are linker (a.2). In some variations of formula (33) described in the paragraphs above, L2, L3, and L4 are linker (a.2). In some variations of formula (33) described in the paragraphs above, LI, L2, L3, and L4 are linker (a.2).
[892] In some variations of formula (33) described in the paragraphs above, at least one of LI , L2, L3, and L4 is linker (b. l):
Figure imgf000280_0001
, in which n is 0-6, rtj is 1-4, and * is the attachment site for the cationic dye moiety D.
[893] In some variations of formula (33) in which at least one of LI, L2, L3, and L4 is linker (b. l ), n is 0-6, 0-5, 0-4, 0-3, 0-2, 0-1, 1-6, 1 -5, 1-4, 1 -3, 1-2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, 5-6, 0, 1, 2, 3, 4, 5, or 6.
[894] In some variations of formula (33) described in the paragraphs above in which at least one of LI, 12, L3, and L4 is linker (b. l), is 1-4, 1 -3, 1-2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[895] In some variations of formula (33) described in the paragraphs above, LI is linker (b. 1). In some variations of formula (33) described in the paragraphs above, L2 is linker (b. l ). In some variations of formula (33) described in the paragraphs above, L3 is linker (b. l ). In some variations of formula (33) described in the paragraphs above, L4 is linker (b. l ). In some variations of formula (33) described in the paragraphs above, LI and L2 are linker (b. l). In some variations of formula (33) descri bed in the paragraphs above, LI and L3 are linker (b. l). In some variations of formula (33) described in the paragraphs above, LI and L4 are linker (b. l). In some variations of formula (33) described in the paragraphs above, L2 and L3 are linker (b. l ). In some variations of formula (33) described in the paragraphs above, L2 and L4 are linker (b. l). In some variations of formula (33) described in the paragraphs above, L3 and L4 are linker (b. l). In some variations of formula (33) described in the paragraphs above, LI, L2, and L3 are linker (b. l). In some variations of formula (33) described in the paragraphs above, LI, L2, and L4 are linker (b. l). In some variations of formula (33) described in the paragraphs above, LI, L3, and L4 are linker (b. l). In some variations of formula (33) described in the paragraphs above, L2, L3, and L4 are linker (b. l). In some variations of formula (33) described in the paragraphs above, LI, L2, L3, and L4 are linker (b. l).
[896] In some variations of formula (33) described in the paragraphs above, at least one of LI, L2, L3, and L4 is linker (c. l):
Figure imgf000281_0001
, in which n is 0-6, «./ is 1-4, either (1) Ra and R¾ independently are H or CH
Figure imgf000281_0002
of CRa-R* are '¾ l ; and * is the attachment site for the cationic dye moiety D.
[897] In some variations of formula (33) in which at least one of LI, L2, L3, and L4 is linker (c. l), n is 0-6, 0-5, 0-4, 0-3, 0-2, 0-1, 1-6, 1-5, 1-4, 1-3, 1-2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, 5-6, 0, 1, 2, 3, 4, 5, or 6.
[898] In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (c. l), m is 1-4, 1-3, 1 -2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[899] In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (c.1), Ra is H and Rj, is H. In some variations of formula (33) described in the paragraphs above in which at least one of Li, L2, L3, and L4 is linker (c. 1), Ra is H and Rb is C¾. In some variations of formula (33) described in the paragraphs above in which at least one of Li, L2, L3, and L4 is linker (c.1), Ra and ¾ are "¾ < in some variations of formula (33) described in the paragraphs above in which at least one of Li, L2, L3, and L4 is
O
linker (c.1), Ra and R¾ are ^ . In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (c.1), two of CRaRb are ¾· .
In some variations of formula (33) described in the paragraphs above in which at least LI, L2, L3, and L4 is linker (c. l), L is ^ } ' ^^^^ζ _
Figure imgf000282_0001
[901] In some variations of formula (33) described in the paragraphs above, LI is linker (c. l). In some variations of formula (33) described in the paragraphs above, L2 is linker (c. l). In some variations of formula (33) described in the paragraphs above, L3 is linker (c. l ). In some variations of formula (33) described in the paragraphs above, L4 is linker (c. l). In some variations of formula (33) described in the paragraphs above, LI and L2 are linker (c. l ). In some variations of formula (33) described in the paragraphs above, LI and L3 are linker (c. l). In some variations of formula (33) described in the paragraphs above, LI and L4 are linker (c. l). In some variations of formula (33) described in the paragraphs above, L2 and L3 are linker (c. l). In some variations of formula (33) described in the paragraphs above, L2 and L4 are linker (c. l). In some variations of formula (33) described in the paragraphs above, L3 and L4 are linker (c. l). In some variations of formula (33) described in the paragraphs above, LI, L2, and L3 are linker (c. l). In some variations of formula (33) described in the paragraphs above, LI, L2, and L4 are linker (c. l). In some variations of formula (33) described in the paragraphs above, LI, L3, and L4 are linker (c. l). In some variations of formula (33) described in the paragraphs above, L2, L3, and L4 are linker (c. l). In some variations of formula (33) described in the paragraphs above, LI, L2, L3, and L4 are linker (c. l). [902] In some variations of formula (33) described in the paragraphs above, at least one of LI, L2, L3, and L4 is linker (c.2):
Figure imgf000283_0001
site for the cationic dye moiety D.
[903] In some variations of formula (33) in which at least one of LI, L2, L3, and L4 is linker (c.2), n is 0-6, 0-5, 0-4, 0-3, 0-2, 0-1, 1-6, 1-5, 1-4, 1-3, 1-2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, 5-6, 0, 1 , 2, 3, 4, 5, or 6.
In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (c.2), n} is 1 -4, 1-3, 1 -2, 2-4, 2-3, 3-4, 1 , 2, 3, or 4.
In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (c.2), Ra is H and Rj, is H. In some variations of formula (. described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (c.2), Ra is H and j, is CI¾. In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (c.2), Ra and R¾ are
Figure imgf000283_0002
]n some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (c.2), Ra and R¾ are
Figure imgf000283_0003
. In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (c.2), two of CRaR¾ are ' V
[906] In some variations of formula (33) described in the ara ra hs above in which at least
Figure imgf000283_0004
one of LI L2, L3, and L4 is linker (c
Figure imgf000283_0005
Figure imgf000284_0001
[907] In some variations of formula (33) described in the paragraphs above, LI is linker (c.2). In some variations of formula (33) described in the paragraphs above, L2 is linker (c.2). In some variations of formula (33) described in the paragraphs above, L3 is linker (c.2). In some variations of formula (33) described in the paragraphs above, L4 is linker (c.2). In some variations of formula (33) described in the paragraphs above, LI and L2 are linker (c.2). In some variations of formula (33) described in the paragraphs above, LI and L3 are linker (c.2). In some variations of formula (33) described in the paragraphs above, LI and L4 are linker (c.2). In some variations of formula (33) described in the paragraphs above, L2 and L3 are linker (c.2). In some variations of formula (33) described in the paragraphs above, L2 and L4 are linker (c.2). In some variations of formula (33) described in the paragraphs above, L3 and L4 are linker (c.2). In some variations of formula (33) described in the paragraphs above, LI, L2, and L3 are linker (c.2). In some variations of formula (33) described in the paragraphs above, LI, L2, and L4 are linker (c.2). In some variations of formula (33) described in the paragraphs above, LI, L3, and L4 are linker (c.2). In some variations of formula (33) described in the paragraphs above, L2, L3, and L4 are linker (c.2). In some variations of formula (33) described in the paragraphs above, LI, L2, L3, and L4 are linker (c.2).
[908] In some variations of formula (33) described in the paragraphs above, at least one of LI, L2, L3, and L4 is linker (d):
Figure imgf000284_0002
, where k is 2-10; (1) Ra and R¾ independently are H or CH3, or (2) Ra and Rj, are O
<r o orr ''¾*· r n orr Π (3) H twwno o off 0 CR¾,a,RRij,. ^ arre. '' < <~· x ; · and * is the attachment site for the cationic dve moiety D.
)9] In some variations of formula (33) in which at least one of LI, L2, L3, and L4 is linker (d), k is 2-10, 2-9, 2-8, 2-7, 2-6, 2-5, 2-4, 2-3, 3-10, 3-9, 3-8, 3-7, 3-6, 3-5, 3-4, 4-10, 4-9, 4-8, 4- 7, 4-6, 4-5, 5-10, 5-9, 5-8, 5-7, 5-6, 6-10, 6-9, 6-8, 6-7, 7-10, 7-9, 7-8, 8-10, 8-9, 9-10, 2, 3, 4, 5, 6, 7, 8. 9, or 10.
[910] In some variations of formul a (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (d), Ra is H and ¾ is H. In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (d), Ra is H and Rj> is ( I f ;. In some variations of formula (33) describe in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (d), Ra and j, are
Figure imgf000285_0001
jn some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (d), Ra and R are
Figure imgf000285_0002
In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (d), two of CRaRb are "^- .
[911] In some variations of formula (33) described in the paragraphs above, LI is linker (d). In some variations of formula (33) described in the paragraphs above, L2 is linker (d). In some variations of formula (33) described in the paragraphs above, L3 is linker (d). In some variations of formula (33) described in the paragraphs above, L4 is linker (d). In some variations of formula (33) described in the paragraphs above, LI and L2 are linker (d). In some variations of formula (33) described in the paragraphs above, LI and L3 are linker (d). In some variations of formula (33) described in the paragraphs above, LI and L4 are linker (d). In some variations of formula (33) described in the paragraphs above, L2 and L3 are linker (d). In some variations of formula (33) described in the paragraphs above, L2 and L4 are linker (d). In some variations of formula (33) described in the paragraphs above, L3 and L4 are linker (d). In some variations of formula (33) described in the paragraphs above, LI, L2, and L3 are linker (d). In some variations of formula (33) described in the paragraphs above, LI, L2, and L4 are linker (d). In some variations of formula (33) described in the paragraphs above, LI, L3, and L4 are linker (d). In some variations of formula (33) described in the paragraphs above, L2, L3, and L4 are linker (d). In some variations of formula (33) described in the paragraphs above, LI, L2, L3, and L4 are linker
(d).
[912] In some variations of formula (33) described in the paragraphs above, at least one of LI, L2, L3, and L4 is linker (e, l ):
Figure imgf000286_0001
(e.r , in which n is 0-6, nj is 1-4, and * is the attachment site for the cationic dye moiety I),
[913] In some variations of formula (33) in which at least one of LI, L2, L3, and L4 is linker (e. l), n is 0-6, 0-5, 0-4, 0-3, 0-2, 0-1, 1-6, 1-5, 1-4, 1-3, 1-2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, 5-6, 0, 1 , 2, 3, 4, 5, or 6.
[914] In some variati ons of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (e. l), m is 1-4, 1-3, 1 -2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[915] In some variations of formula (33) described in the paragraphs above, LI is linker (e. l). In some variations of formula (33) described in the paragraphs above, L2 is linker (e. l). In some variations of formula (33) described in the paragraphs above, L3 is linker (e. l). In some variations of formula (33) described in the paragraphs above, L4 is linker (e. l). In some variations of formula (33) described in the paragraphs above, LI and L2 are linker (e. l ). In some variations of formula (33) described in the paragraphs above, LI and L3 are linker (e. l). In some variations of formula (33) described in the paragraphs above, LI and L4 are linker (e. l ). In some variations of formula (33) described in the paragraphs above, L2 and L3 are linker (e. l). In some variations of formula (33) described in the paragraphs above, L2 and L4 are linker (e. l ). In some variations of formula (33) described in the paragraphs above, L3 and L4 are linker (e. l ). In some vari ations of formula (33) described in the paragraphs above, LI, L2, and L3 are linker (e. l). In some variations of formula (33) described in the paragraphs above, LI, L2, and L4 are linker (e. l ). In some variations of formula (33) described in the paragraphs above, LI, L3, and L4 are linker (e. l). In some variations of formula (33) described in the paragraphs above, L2, L3, and L4 are linker (e. 1). In some variations of formula (33) described in the paragraphs above, LI, L2, L3, and L4 are linker (e. l ).
[916] In some variations of formula (33) described in the paragraphs above, at least one of LI, L2, L3, and L4 is linker (f. I):
Figure imgf000286_0002
, in which n} is 0-5, n2 is 1-5, and * is the attachment site for the cationic e moiety D. [917] In some variations of formula (33) in which at least one of LI, L2, L3, and L4 is linker (f. l), ni is 0-5, 0-4, 0-3, 0-2, 0-1, 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1, 2, 3, 4, or 5.
[918] In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 i s linker (f. l), n2 is 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5.
[919] In some variations of formula (33) described in the paragraphs above, LI is linker (f.1). In some variations of formula (33) described in the paragraphs above, L2 is linker (f.1). In some variations of formula (33) described in the paragraphs above, L3 is linker (f. l). In some variations of formula (33) described in the paragraphs above, L4 is linker (f. l). In some variations of formula (33) described in the paragraphs above, LI and L2 are linker (f. 1). In some variations of formula (33) described in the paragraphs above, LI and L3 are linker (f. l). In some variations of formula (33) described in the paragraphs above, LI and L4 are linker (f. l). In some variations of formula (33) described in the paragraphs above, L2 and L3 are linker (f. l). In some variations of formula (33) described in the paragraphs above, L2 and L4 are linker (f. 1). In some variations of formula (33) described in the paragraphs above, L3 and L4 are linker (f. l). In some variations of formula (33) described in the paragraphs above, LI, L2, and L3 are linker (f. l). In some variations of formula (33) described in the paragraphs above, LI, L2, and L4 are linker (f.1). In some variations of formula (33) described in the paragraphs above, LI, L3, and L4 are linker (f. l ). In some variations of formula (33) described in the paragraphs above, L2, L3, and L4 are linker (f. l). In some variations of formula (33) described in the paragraphs above, LI, L2, L3, and L4 are linker (f. l ).
[920] In some variati ons of formula (33) described in the paragraphs above, at least one of LI, L2, L3, and L4 is linker i f.2):
Figure imgf000287_0001
, in which is 0-5, n? is 1-5, and * is the attachment site for the cationic dye moiety D.
[921] In some variations of formula (33) in which at least one of LI, L2, L3, and L4 is linker (f.2), m is 0-5, 0-4, 0-3, 0-2, 0-1 , 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1 , 2, 3, 4, or 5. [922] In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (f.2), n2 is 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5,
[923] In some variations of formula (33) described in the paragraphs above, LI is linker (f.2). In some variations of formula (33) described in the paragraphs above, L2 is linker (f.2). In some variations of formula (33) described in the paragraphs above, L3 is linker (f.2). In some variations of formula (33) described in the paragraphs above, L4 is linker (f.2). In some variations of formula (33) described in the paragraphs above, LI and L2 are linker (f.2). In some variations of formula (33) described in the paragraphs above, LI and L3 are linker (f.2). In some variations of formula (33) described in the paragraphs above, LI and L4 are linker (f.2). In some variations of formula (33) described in the paragraphs above, L2 and L3 are linker (f.2). In some variations of formula (33) described in the paragraphs above, L2 and L4 are linker (f.2). In some variations of formula (33) described in the paragraphs above, L3 and L4 are linker (f.2). In some variations of formula (33) described in the paragraphs above, LI, L2, and L3 are linker (f.2). In some variations of formula (33) described in the paragraphs above, LI, L2, and L4 are linker (f.2). In some variations of formula (33) described in the paragraphs above, LI, L3, and L4 are linker (f.2). In some variations of formula (33) described in the paragraphs above, L2, L3, and L4 are linker (f.2). In some variations of formula (33) described in the paragraphs above, LI, L2, L3, and L4 are linker (f.2).
[924] In some variations of formula (33) described in the paragraphs above, at least one of LI, L2, L3, and L4 is linker (g. l):
Figure imgf000288_0001
(g- 1 ) , in which n} is 0-5, n2 is 1-5, and * is the attachment site for the cationic dye moiety I),
[925] In some variations of formula (33) in which at least one of LI, L2, L3, and L4 is linker (g. l), nj is 0-5, 0-4, 0-3, 0-2, 0-1, 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1, 2, 3, 4, or 5.
[926] In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (g. l), n2 is 1 -5, 1-4, 1 -3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2,
3, 4, or 5. [927] In some variations of formula (33) described in the paragraphs above, LI is linker (g.1). In some variations of formula (33) described in the paragraphs above, L2 is linker (g. l). In some vari ations of formula (33) described in the paragraphs above, L3 is linker (g.1). In some variations of formula (33) described in the paragraphs above, L4 is linker (g. l). In some variations of formula (33) described in the paragraphs above, LI and L2 are linker (g. l). In some variations of formula (33) described in the paragraphs above, LI and L3 are linker (g. l). In some variations of formula (33) described in the paragraphs above, LI and L4 are linker (g. l). In some variations of formula (33) described in the paragraphs above, L2 and L3 are linker (g. l). In some variations of formula (33) described in the paragraphs above, L2 and L4 are linker (g. l). In some variations of formula (33) described in the paragraphs above, L3 and L4 are linker (g. l). In some variations of formula (33) described in the paragraphs above, LI, L2, and L3 are linker (g.1). In some variations of formula (33) described in the paragraphs above, LI, L2, and L4 are linker (g. l). In some variations of formula (33) described in the paragraphs above, LI, L3, and L4 are linker (g. l). In some variations of formula (33) described in the paragraphs above, L2, L3, and L4 are linker (g. l ). In some variations of formula (33) described in the paragraphs above, LI, L2, L3, and L4 are linker (g.1).
[928] In some variations of formula (33) described in the paragraphs above, at least one of LI, L2, L3, and L4 is linker (g.2):
Figure imgf000289_0001
(9-2) , in which ¾/ is 0-5, n? is 1-5, and * is the attachment site for the cationic dve moiety D.
[929] In some variations of formula (33) in which at least one of LI, L2, L3, and L4 is linker (g.2), n} is 0-5, 0-4, 0-3, 0-2, 0-1, 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1, 2, 3, 4, or 5.
[930] In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (g.2), n2 is 1-5, 1 -4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1 , 2, 3, 4, or 5.
[931] In some variations of formula (33) described in the paragraphs above, LI is linker (g.2). In some variations of formula (33) described in the paragraphs above, L2 is linker (g.2). In some variations of formula (33) described in the paragraphs above, L3 is linker (g.2). In some variations of formula (33) described in the paragraphs above, L4 is linker (g.2). In some variations of formula (33) described in the paragraphs above, LI and L2 are linker (g.2). In some variations of formula (33) described in the paragraphs above, LI and L3 are linker (g.2). In some variations of formula (33) described in the paragraphs above, LI and L4 are linker (g.2). In some variations of formula (33) described in the paragraphs above, L2 and L3 are linker (g.2). In some variations of formula (33) described in the paragraphs above, L2 and L4 are linker (g.2). In some variations of formula (33) described in the paragraphs above, L3 and L4 are linker (g.2). In some variations of formula (33) described in the paragraphs above, LI, L2, and L3 are linker (g.2). In some variations of formula (33) described in the paragraphs above, LI, L2, and L4 are linker (g.2). In some variations of formula (33) described in the paragraphs above, LI , L3, and L4 are linker (g.2). In some variations of formula (33) described in the paragraphs above, L2, L3, and L4 are linker (g.2). In some variations of formula (33) described in the paragraphs above, LI, L2, L3, and L4 are linker (g.2).
[932 ] In some variations of formula (33) described in the paragraphs above, at least one of LI, L2, L3, and L4 is linker (h. I):
Figure imgf000290_0001
(h.1 ) , in which n} is 0-5, n2 is 1-5, and * is the attachment site for the cationic dye moiety I),
[933] In some variations of formula (33) in which at least one of LI, L2, L3, and L4 is linker (h. I), fit is 0-5, 0-4, 0-3, 0-2, 0-1, 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1, 2, 3, 4, or 5.
[934] In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (h. I), n2 is 1-5, 1 -4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1 , 2,
3, 4, or 5.
[935] In some variations of formula (33) described in the paragraphs above, LI is linker (h. I). In some variations of formula (33) described in the paragraphs above, L2 is linker (h. I). In some variations of formula (33) described in the paragraphs above, L3 is linker (h. I ). In some variations of formula (33) described in the paragraphs above, L4 is linker (h. I). In some variations of formula (33) descri bed in the paragraphs above, LI and L2 are linker (h. I), In some variations of formula (33) described in the paragraphs above, LI and L3 are linker (h. I). In some variations of formula (33) described in the paragraphs above, LI and L4 are linker (h. l). In some variations of formula (33) described in the paragraphs above, L2 and L3 are linker (h. l). In some variations of formula (33) described in the paragraphs above, L2 and L4 are linker (h. l). In some variations of formula (33) described in the paragraphs above, L3 and L4 are linker (h. l). In some variations of formula (33) described in the paragraphs above, LI, L2, and L3 are linker (h. l). In some variations of formula (33) described in the paragraphs above, LI, L2, and L4 are linker (h. l). In some variations of formula (33) described in the paragraphs above, LI, L3, and L4 are linker (h. l ). In some variations of formula (33) described in the paragraphs above, L2, L3, and L4 are linker (h. l). In some variations of formula (33) described in the paragraphs above, LI, L2, L3, and L4 are linker (h. l ).
[936] In some variations of formula (33) described in the paragraphs above, at least one of LI , L2, L3, and L4 is linker (h.2):
Figure imgf000291_0001
(h.2) ^ jn ^γ^ς^ Rl is Q-53 ¾, js I„55 an(j * is†he attachment site for the cationic dye moiety D.
[937] In some variations of formula (33) in which at least one of LI, L2, L3, and L4 is linker (h.2), m is 0-5, 0-4, 0-3, 0-2, 0-1, 1-5, 1-4, 1-3, 1 -2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1, 2, 3, 4, or 5,
[938] In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (h.2), n2 is 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5,
[939] In some variations of formula (33) described in the paragraphs above, LI is linker (h.2). In some variations of formula (33) described in the paragraphs above, L2 is linker (h.2). In some variations of formula (33) described in the paragraphs above, L3 is linker (h.2). In some variations of formula (33) described in the paragraphs above, L4 is linker (h.2). In some variations of formula (33) described in the paragraphs above, LI and L2 are linker (h.2). In some variations of formula (33) described in the paragraphs above, LI and L3 are linker (h.2). In some variations of formula (33) described in the paragraphs above, LI and L4 are linker (h.2). In some variations of formula (33) described in the paragraphs above, L2 and L3 are linker (h.2). In some variations of formula (33) described in the paragraphs above, L2 and L4 are linker (h.2). In some variations of formula (33) described in the paragraphs above, L3 and L4 are linker (h.2). In some variations of formula (33) described in the paragraphs above, LI, L2, and L3 are linker (h.2). In some variations of formula (33) described in the paragraphs above, LI, L2, and L4 are linker (h.2). In some variations of formula (33) described in the paragraphs above, LI, L3, and L4 are linker (h.2). In some variations of formula (33) described in the paragraphs above, L2, L3, and L4 are linker (h.2). In some variations of formula (33) described in the paragraphs above, LI, L2, L3, and L4 are linker (h.2).
[940] In some variations of formula (33) described in the paragraphs above, at least one of LI, L2, L3, and L4 is linker (i. l):
Figure imgf000292_0001
, in which nj and ¾ independently are 1-5 and * is the attachment site for the cationic dye moiety D.
[941] In some variations of formula (33) described in the paragraphs above, at least one of LI, L2, L3, and L4 is linker (i. l), m i s 1 -5, 1-4, 1 -3, 1 -2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5.
[942] In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (i. l), m is 1-5, 1 -4, 1-3, 1 -2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1 , 2, 3, 4, or 5.
[943] In some variations of formula (33) described in the paragraphs above, LI is linker (i. l). In some variations of formula (33) described in the paragraphs above, L2 is linker (i. l). In some variations of formula (33) described in the paragraphs above, L3 is linker (i. l). In some variations of formula (33) described in the paragraphs above, L4 is linker (i. l). In some variations of formula (33) described in the paragraphs above, LI and L2 are linker (i. l). In some variations of formula (33) described in the paragraphs above, LI and L3 are linker (i. l ). In some variations of formula (33) described in the paragraphs above, LI and L4 are linker (i. l). In some variations of formula (33) described in the paragraphs above, L2 and L3 are linker (i. l). In some variations of formula (33) described in the paragraphs above, L2 and L4 are linker (i. l). In some variations of formula (33) described in the paragraphs above, L3 and L4 are linker (i. l ). In some variations of formula (33) described in the paragraphs above, LI, L2, and L3 are linker (i. l). In some variations of formula (33) described in the paragraphs above, LI, L2, and L4 are linker (i. l). In some variations of formula (33) described in the paragraphs above, LI, L3, and L4 are linker (i . l ). In some variations of formula (33) described in the paragraphs above, L2, L3, and L4 are linker (i. l). In some variations of formula (33) described in the paragraphs above, LI, L2, L3, and L4 are linker (i. 1).
[944] In some variations of formula (33) described in the paragraphs above, at least one of LI, L2, L3, and L4 is linker (i.2):
Figure imgf000293_0001
{-LZ> , in which n} and n2 independently are 1-5 and * is the attachment site for the cationic dye moiety D.
[945] In some variations of formula (33) described in the paragraphs above, at least one of LI , L2, L3, and L4 is linker (i.2), «? is 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5.
[946] In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (i.2), m is 1-5, 1 -4, 1-3, 1 -2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1 , 2, 3, 4, or 5.
[947 ] In some variations of formula (33) described in the paragraphs above, LI is linker (i.2). In some variations of formula (33) described in the paragraphs above, L2 is linker (i.2). In some variations of formula (33) described in the paragraphs above, L3 is linker (i.2). In some variations of formula (33) described in the paragraphs above, L4 is linker (i.2). In some variations of formula (33) described in the paragraphs above, LI and L2 are linker (i .2). In some variations of formula (33) described in the paragraphs above, LI and L3 are linker (i.2). In some variations of formula (33) described in the paragraphs above, LI and L4 are linker (i.2). In some variations of formula (33) described in the paragraphs above, L2 and L3 are linker (i.2). In some variations of formula (33) described in the paragraphs above, L2 and L4 are linker (i.2). In some variations of formula (33) described in the paragraphs above, L3 and L4 are linker (i.2). In some variations of formula (33) described in the paragraphs above, LI, L2, and L3 are linker (i.2). In some variations of formula (33) described in the paragraphs above, LI, L2, and L4 are linker (i.2). In some variations of formula (33) described in the paragraphs above, LI, L3, and L4 are linker (i.2). In some variations of formula (33) described in the paragraphs above, L2, L3, and L4 are linker (i.2). In some variations of formula (33) described in the paragraphs above, LI, L2, L3, and L4 are linker (i .2). [948] In some variations of formula (33) described in the paragraphs above, at least one of LI, L2, L3, and L4 is linker (j.l):
Figure imgf000294_0001
which «2 is 1-5 and * is the attachment site for the cationic dye moiety D.
[949] In some variations of formula (33) in which at least one of LI, L2, L3, and L4 is linker (j.l), n2 is 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5.
[950] In some variations of formula (33) described in the paragraphs above, LI is linker (j.l). In some variations of formula (33) described in the paragraphs above, L2 is linker (j.l). In some variations of formula (33) described in the paragraphs above, L3 is linker (j.l). In some variations of formula (33) described in the paragraphs above, L4 is linker (j.l). In some variations of formula (33) described in the paragraphs above, LI and L2 are linker (j.l). In some variations of formula (33) described in the paragraphs above, LI and L3 are linker (j.l). In some variations of formula (33) described in the paragraphs above, LI and L4 are linker (j.l). In some variations of formula (33) described in the paragraphs above, L2 and L3 are linker (j.l). In some variations of formula (33) described in the paragraphs above, L2 and L4 are linker (j.l). In some variations of formula (33) described in the paragraphs above, L3 and L4 are linker (j.l). In some variations of formula (33) described in the paragraphs above, LI, L2, and L3 are linker (j.l). In some vari ations of formula (33) described in the paragraphs above, LI, L2, and L4 are linker (j.l). In some variations of formula (33) described in the paragraphs above, LI, L3, and L4 are linker (j.l). In some variations of formula (33) described in the paragraphs above, L2, L3, and L4 are linker (j.l). In some variations of formula (33) described in the paragraphs above, LI, L2, L3, and L4 are linker (j.l). [951] In some variations of formula (33) described in the paragraphs above, at least one of LI , L2, L3, and L4 is linker (j .2):
Figure imgf000295_0001
(j.2) , in which n2 is 1 -5 and * is the attachment site for the cationic dye moiety D.
[952] In some variations of formula (33) in which at least one of LI, L2, L3, and L4 is linker (j .2), n2 is 1-5, 1 -4, 1-3, 1 -2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1 , 2, 3, 4, or 5.
[953] In some variations of formula (33) described in the paragraphs above, LI is linker (j .2). In some variations of formula (33) described in the paragraphs above, L2 is linker (j .2). In some variations of formula (33) described in the paragraphs above, L3 is linker (j , 2). In some variations of formula (33) described in the paragraphs above, L4 is linker (j .2). In some variations of formula (33) described in the paragraphs above, LI and L2 are linker (j .2). In some variations of formula (33) described in the paragraphs above, LI and L3 are linker (j .2). In some variations of formula (33) described in the paragraphs above, LI and L4 are linker (j .2). In some variations of formula (33) described in the paragraphs above, L2 and L3 are linker (j .2). In some variations of formula (33) described in the paragraphs above, L2 and L4 are linker (j .2). In some variations of formula (33) described in the paragraphs above, L3 and L4 are linker (j .2). In some variations of formula (33) described in the paragraphs above, LI, L2, and L3 are linker (j .2). In some vari ations of formula (33) described in the paragraphs above, LI, L2, and L4 are linker (j .2). In some variations of formula (33) described in the paragraphs above, LI, L3, and L4 are linker (j .2). In some variations of formula (33) described in the paragraphs above, L2, L3, and L4 are linker (j .2). In some variations of formula (33) described in the paragraphs above, LI, L2, L3, and L4 are linker (j .2). [954] In some variations of formula (33) described in the paragraphs above, at least one of LI, L2, L3, and L4 is linker (k):
Figure imgf000296_0001
^ , in which li and independently are 1-4, n is 1-4; ring A is aryl, heteroaryl, cycloalkyl, or heterocyclyl; (1) Rai and Rbi independently are H or CH3 or (2) RaX and j>i independently are ) Ra2 and j>2 independently are H or CH
Figure imgf000296_0002
3 or (2) RA2 and Κ¾2 independently are ; or (3) two of
CRa2Rb2 are '^- ; and * is the attachment site for the cationic dye moiety I),
[955] In some variations of formula (33) in which at least one of LI, L2, L3, and L4 is linker (k), is 1-4, 1-3, 1-3, 1-2, 2-4, 2-3, 3-4, I, 2, 3, or 4.
[956] In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 i s linker (k), l2 is 1-4, 1 -3, 1-3, 1-2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[957] In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 i s linker (k), Rai is H and R¾i is H. In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (k), RAI is H and RM is CH3. In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (k), Rai and RM are "¾ . In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is
O
linker (k), Rai and RM are "¾ . In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (k), two of CRaiRw are
[958] In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (k), Ra2 is H and (,2 is H. In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (k), R^ is H and Rj,2 is CH3. In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (k), Ra2 and ¾2 are "¾ . In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is
O
linker (k), Ra2 and ¾2 are "¾ ^\ In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (k), two of CRa2Ri>2 are
[959] In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (k), ring A is
Figure imgf000297_0001
optionally substituted with halo or C1 -C6 linear or branched aikyl;
Figure imgf000297_0002
optionally substituted with halo or C1 -C6 linear or branched alkyl; or
Figure imgf000297_0003
Figure imgf000298_0001
optionally substituted with halo or C 1 -C6 linear or branched alkyl .
[960] In some variations of formula (33) described in the paragraphs above in which L is linker (k), ring A is substituted with halo. In some variations, the halo is F, Br, I, or CI.
[961 ] In some variations of formula (33) described in the paragraphs above in which L is linker (k), ring A is substituted with C 1 -C6 linear or branched alkyl (e.g., C 1-C6, C 1-C5, C 1 -C4, C l- C3, C 1-C2, C I , C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl).
[962] In some variations of formula (33) described in the paragraphs above, LI i s linker (k). In some variations of formula (33) described in the paragraphs above, L2 is linker (k). In some variations of formula (33) described in the paragraphs above, L3 is linker (k). In some variations of formula (33) described in the paragraphs above, 3L4 is linker (k). In some variations of formula (33) described in the paragraphs above, LI and L2 are l inker (k). In some variations of formula (33) described in the paragraphs above, LI and L3 are linker (k). In some variations of formula (33) described in the paragraphs above, LI and L4 are linker (k). In some variations of formula (33) described in the paragraphs above, L2 and L3 are linker (k). In some variations of formula (33) described in the paragraphs above, L2 and L4 are linker (k). In some variations of formula (33) described in the paragraphs above, L3 and L4 are linker (k). In some variations of formula (33) described in the paragraphs above, LI, L2, and L3 are linker (k). In some variations of formula (33) described in the paragraphs above, LI, L2, and L4 are linker (k). In some variations of formula (33) described in the paragraphs above, LI, L3, and L4 are linker (k). In some variations of formula (33) described in the paragraphs above, L2, L3, and L4 are linker (k). In some variations of formula (33) described in the paragraphs above, LI , L2, L3, and L4 are linker (k).
S3] In some variations of formula (33) described in the paragraphs above, at least one of LI, L2, L3, and L4 is linker (1.1):
Figure imgf000299_0001
-l , in which i , l2, n, o , and o2 independently are 1-4; risig A is aryl, heteroaryl, cycloalkyl, or heterocyclyl; for each independent instance of Rai and
Rbi. Rai an R i( ) independently are II or CH3, or (2) Rai and j,i independently are
Figure imgf000299_0002
or 0
or (3) two of CRaiRbi are ¼^% ;· for each independent instance of Ra2 and RM, a2 and
*— O
; 1) independently are H or CH3, or (2) Ra2 and j,2 independently are or ' *· , or (3) two of C a2 |g,2 are " for each independent instance of ci and Rtu, R«i and Rai ( 1
O
independently are H or CH3, or (2) ^ and ¾{ independently are '¾ or <- , or (3) two of
LMtiKAi are , for each independent instance of Rc2 and RD2I Rc2 and (j2 (1)
Y— 7 O ^
independently are H or CH3, or (2) and R^z independently are " ¾ o orrΛ or (3) two c2 d2 are ' 1 x ; and * is the attachment site for the cationic dye moietv [964] In some variations of formula (33) in which at least one of LI, L2, L3, and L4 is linker (1.1), h is 1-4, 1-3, 1-3, 1-2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[965] In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 i s linker (1.1), h i s 1-4, 1-3, 1-3, 1-2, 2-4, 2-3, 3-4, 1 , 2, 3, or 4,
In some variations of formula (33) described in the paragraphs above in which at one of LI, L2, L3, and L4 is linker (1.1), oj is 1-4, 1-3, 1-3, 1-2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[967 ] In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.1), o2 is 1-4, 1-3, 1-3, 1-2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[968] In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.1), Ra3 is H and ¾i is H. In some variations of formula (33) described in the paragraphs above in which at least one of Li, L2, L3, and L4 is linker (1.1), Rai is H and ]½ is CH3. In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.1), RAJ and &j are "¾ . In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3,
O
and L4 is linker (1.1), Rai and RM are '¾ In some variations of formula (33) described in the paragraphs above in whi ch at least one of LI, L2, L3, and L4 is linker (1.1), two of CRaiRbi are
[969] In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 i s linker (1.1), a2 is H and R1(2 is H. In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.1), R¾2 is H and ¾2 is C¾. In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.1), Ra2 and ¾2 are
Figure imgf000300_0001
· In some variations of formula (33) described in the paragraphs above in which at least one of LI , L2, L3,
O
and L4 is linker (1.1), RA2 and Rj,2 are " ^\ In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.1 ), two of C ^KM are [970] In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.1), R^ is H and R^i is H. In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.1 ), Rei is H and Rui is C¾. In some variations of formula (33) described in the paragraphs above in
Figure imgf000301_0001
which at least one of LI, L2, L3, and L4 is linker (1.1), . In some variations of formula (33) described in the paragraphs above in which at least one of LI , L2, L3, and L4 is linker (1. 1), Rci and R(U are
Figure imgf000301_0002
In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.1), two of CRciRdi are
[971 ] In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.1), Rc2 is H and ,¾2 is H. In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.1), Rc2 is H and d2 is CH . In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.1), Rc2 and ¾2 are "¾ . In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3,
9
and L4 is linker (1.1), Re? and R&2 are *" . In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.1), two of CRC2 d2 are
[972] In some variations of formula (33) described in the paragraphs above in which at one of LI , L2, L3, and L4 is linker (1.1), ring A is
Figure imgf000301_0003
optionally substituted with halo or C1-C6 linear or branched aikyl;
Figure imgf000301_0004
optionally substituted with halo or C1-C6 linear or branched aikyl; or
Figure imgf000302_0001
301
Figure imgf000303_0001
optionally substituted with halo or CI -C6 linear or branched aiky! ,
[973] In some variations of formula (33) described in the paragraphs above in which L is linker (1.1 ), ring A is substituted with halo. In some variations, the halo is F, Br, I, or CI.
[974] In some variations of formula (33) described in the paragraphs above in which L is linker (1.1 ), ring A is substituted with C1-C6 linear or branched al kyl (e.g., C1 -C6, C 1-C5, C 1-C4, Cl - C3, C 1-C2, C I , C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl).
[975] In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.1), n is 1-4, 1 -3, 1-3, 1 -2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[976] In some variations of formula (33) described in the paragraphs above, LI is linker (1.1). In some variations of formula (33) described in the paragraphs above, L2 is linker (1 , 1 ). In some variations of formula (33) described in the paragraphs above, L3 is linker (1.1). In some variations of formula (33) described in the paragraphs above, L4 is linker (1, 1 ). In some variations of formula (33) described in the paragraphs above, LI and L2 are linker (1. 1). In some variations of formula (33) described in the paragraphs above, LI and L3 are linker (1.1). In some variations of formula (33) described in the paragraphs above, LI and L4 are linker (1.1). In some variations of formula (33) described in the paragraphs above, L2 and L3 are linker (1. 1 ). In some variations of formula (33) described in the paragraphs above, L2 and L4 are linker (1.1 ). In some variations of formula (33) described in the paragraphs above, L3 and L4 are linker (1. 1). In some variations of formula (33) described in the paragraphs above, LI, L2, and L3 are linker (1.1). In some variations of formula (33) described in the paragraphs above, LI, L2, and L4 are linker (1.1 ). In some variations of formula (33) described in the paragraphs above, LI, L3, and L4 are linker (1.1). In some variations of formula (33) described in the paragraphs above, L2, L3, and L4 are linker (1.1). In some variations of formula (33) described in the paragraphs above, LI, L2, L3, and L4 are linker (1.1).
[977] In some variations of formula (33) described in the paragraphs above, at least one of LI, L2, L3, and L4 is linker (1.2):
Figure imgf000304_0001
!^2^ , in which l , n, ® and o2 independently are 1.-4; ring A is aryl, heteroaryl, cycloalkvl, or heterocvclyl; for each independent instance of Rai and
Rbi, Rai and Rbi(l) independently are H or CH3, or (2) ai and M independently are "¾ or or (3) two of CRaiRbi are ^ ^ ^ for each independent instance of Ra2 and Rb2, a2 and
■Rb2 (1 ) independently are H or CH3, or (2) Ra2 and Rj>2 independently are
Figure imgf000304_0002
or (3) two of CRa2Rb2 are "^- ; for each independent instance of ^ and R<U j ^ and Kdi (1)
O
independently are H or CH3, or (2) Rcl and ^i independently are " or '¾ or (3) two of CRciRai are "^- ; for each independent instance of R^ and ^, Rci and Ra2 ( ) independently are H or CH , or (2) c2 and ¾2 independently are
Figure imgf000304_0003
CRc2Rd2 are " ·· , and * is the attachment site for the cationic dye moiety D.
[978] In some variations of formula (33) in which at least one of LI, L2, L3, and L4 is linker (1.2), h is 1 -4, 1-3, 1 -3, 1-2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[979] In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.2), h is 1-4, 1-3, 1-3, 1-2, 2-4, 2-3, 3-4, I, 2, 3, or 4.
[980] In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.2), oi is 1-4, 1 -3, 1-3, 1 -2, 2-4, 2-3, 3-4, 1 , 2, 3, or 4,
[981] In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.2), o2 is 1-4, 1-3, 1-3, 1-2, 2-4, 2-3, 3-4, 1 , 2, 3, or 4.
[982] In some variations of formul a (33) described in the paragraphs above in which at l east one of LI, L2, L3, and L4 is linker (1.2), ai is H and ¾i is H. In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.2), Rai is H and R¾i is CH3. In some variations of formula (33) described in the paragraphs above in which at least one ot LI, L2, L3, and L4 is linker (1.2), Rai and R1(i are
Figure imgf000305_0001
. In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3,
p
and L4 is linker (1.2), Rai and R¾i are '¾ . In some variations of tormula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.2), two of CRaiRbi are
[983] In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.2), Ra2 is H and ¾2 is H. In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.2), Ra2 is H and Rj>2 is CH3. In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.2), Ra2 and Rb2 are "^- . In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3,
O
and L4 is linker (1.2), Ra2 and .¾)2 are In some variations of formula (33) described in the hs above in which at least one of LI, L2, L3, and L4 is linker (1.2), two of C a2Rb2 are
Figure imgf000305_0002
[984] In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.2), ^ is H and R,u is H. In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.2), et is H and ^i is CH3. In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.2), ct and ¾{ are "¾ . In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.2),
Figure imgf000305_0003
variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.2), two of CRciRdi are
[985] In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.2), Rc2 is H and Ι¾2 is H. In some variations of formula (33) described in the paragraphs above in which at least one of Li, L2, L3, and L4 is linker (1.2), Rc2 is H and ¾2 is G¾. In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.2), Rc2 and ¾2 are "¾ ^ . In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3,
9
and L4 is linker (1.2), and are In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.2), two of
Figure imgf000306_0001
are
[986] In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.2), ring A is
Figure imgf000306_0002
optionally substituted halo or C1-C6 linear or branched alkyl;
Figure imgf000306_0003
optionally substituted with halo or C1-C6 linear or branched alkyl; or
Figure imgf000306_0004
Figure imgf000307_0001
optionally substituted with halo or C 1-C6 linear or branched alkyl.
[987] In some variations of formula (33) described in the paragraphs above in which L is linker (1.2), ring A is substituted with halo. In some variations, the halo is F, Br, I, or CI.
[988] In some variations of formula (33) described in the paragraphs above in which L is linker (1.2), ring A is substituted with C1-C6 linear or branched alkyl (e.g., C1-C6, C 1-C5, C 1 -C4, C l- C3, C 1-C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl).
[989] In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.2), n is 1 -4, 1-3, 1 -3, 1-2, 2-4, 2-3, 3-4, 1 , 2, 3, or 4. [990] In some variations of formula (33) described in the paragraphs above, LI is linker (1.2). In some variations of formula (33) described in the paragraphs above, L2 is linker (1.2). In some variations of formula (33) described in the paragraphs above, L3 is linker (1.2). In some variations of formula (33) described in the paragraphs above, L4 is linker (1.2). In some variations of formula (33) described in the paragraphs above, LI and L2 are linker (1.2). In some variations of formula (33) described in the paragraphs above, LI and L3 are linker (1.2). In some variations of formula (33) described in the paragraphs above, LI and L4 are linker (1.2). In some variations of formula (33) described in the paragraphs above, L2 and L3 are linker (1.2). In some variations of formula (33) described in the paragraphs above, L2 and L4 are linker (1.2). In some variations of formula (33) described in the paragraphs above, L3 and L4 are linker (1.2). In some variations of formula (33) described in the paragraphs above, LI, L2, and L3 are linker (1.2). In some variations of formula (33) described in the paragraphs above, LI, L2, and L4 are linker (1.2). In some variations of formula (33) described in the paragraphs above, LI, L3, and L4 are linker (1.2). In some variati ons of formula (33) described in the paragraphs above, L2, L3, and L4 are linker (1.2). In some variations of formula (33) described in the paragraphs above, LI, L2, L3, and L4 are linker (1.2).
[991] In some variations of formula (33) described in the paragraphs above, at least one of LI, L2, L3, and L4 is linker (m. l):
Figure imgf000308_0001
, in which n is 0-6, n? is 1-4, and * is the attachment site for the cationic dye moiety D.
[992] In some variations of formula (33) in which at least one of LI, L2, L3, and L4 is linker (m. l), n is 0-6, 0-5, 0-4, 0-3, 0-2, 0-1, 1-6, 1-5, 1-4, 1-3, 1-2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, 5-6, 0, 1 , 2, 3, 4, 5, or 6.
[993] In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (m. l), n} is 1-4, 1-3, 1-2, 2-4, 2-3, 3-4, I, 2, 3, or 4.
I] In some variations of formula (33) described in the paragraphs above, LI is linker (m.1). In some variations of formula (33) described in the paragraphs above, L2 is linker (m. l). In some variations of formula (33) described in the paragraphs above, L3 is linker (m. l). In some variations of formula (33) described in the paragraphs above, L4 is linker (m. l). In some variations of formula (33) described in the paragraphs above, LI and L2 are linker (m. l ). In some variations of formula (33) described in the paragraphs above, LI and L3 are linker (m.1). In some variations of formula (33) described in the paragraphs above, LI and L4 are linker (m. l). In some variations of formula (33) described in the paragraphs above, L2 and L3 are linker (m. l). In some variations of formula (33) described in the paragraphs above, L2 and L4 are linker (m. l). In some variations of formula (33) described in the paragraphs above, L3 and L4 are linker (m.1). In some variations of formula (33) described in the paragraphs above, LI, L2, and L3 are linker (m. l). In some variations of formula (33) described in the paragraphs above, LI, L2, and L4 are linker (m.1). In some variations of formula (33) described in the paragraphs above, LI , L3, and L4 are linker (m. l). In some variations of formula (33) described in the paragraphs above, L2, L3, and L4 are linker (m. l). In some variations of formula (33) described in the paragraphs above, LI, L2, L3, and L4 are linker (m. l).
[995] In some variations of formula (33) described in the paragraphs above, at least one of LI, L2, L3, and L4 is linker (n. 1):
Figure imgf000309_0001
(n.1) , in which n2 is 1-5 and * is the attachment site for the cationic dye moiety D.
[996] In some variations of formula (33) in which at least one of LI, L2, L3, and L4 is linker (n. l), n2 is 1 -5, 1-4, 1 -3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5,
[997] In some variations of formula (33) described in the paragraphs above, Li is linker (n. l). In some variations of formula (33) described in the paragraphs above, L2 is linker (n. l). In some variations of formula (33) described in the paragraphs above, L3 is linker (n. l ). In some variations of formula (33) described in the paragraphs above, L4 is linker (n. l). In some variations of formula (33) described in the paragraphs above, LI and L2 are linker (n. l). In some variations of formula (33) described in the paragraphs above, LI and L3 are linker (n. l). In some variations of formula (33) described in the paragraphs above, LI and L4 are linker (n. l). In some variations of formula (33) described in the paragraphs above, L2 and L3 are linker (n. l). In some variations of formula (33) described in the paragraphs above, L2 and L4 are linker (n. l). In some variations of formula (33) described in the paragraphs above, L3 and L4 are linker (n. l). In some variations of formula (33) described in the paragraphs above, LI, L2, and L3 are linker (n. l). In some variations of formula (33) described in the paragraphs above, LI, L2, and L4 are linker (n. l). In some variations of formula (33) described in the paragraphs above, LI, L3, and L4 are linker (n. l). In some variations of formula (33) described in the paragraphs above, L2, L3, and L4 are linker (n. l ). In some variations of formula (33) described in the paragraphs above, LI, L2, L3, and L4 are linker (n.1).
[998] In some variations of formula (33) described in the paragraphs above, at least one of LI, L2, L3, and L4 is linker (n.2):
Figure imgf000310_0001
(n.2) , in which n2 is 1 -5 and * is the attachment site for the cationic dye moiety D.
[999] In some variations of formula (33) in which at least one of LI, L2, L3, and L4 is linker (n.2), n2 is 1-5, 1 -4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1 , 2, 3, 4, or 5.
[1000] In some variations of formula (33) described in the paragraphs above, LI is linker (n.2). In some variations of formula (33) described in the paragraphs above, L2 is linker (n.2). In some variations of formula (33) described in the paragraphs above, L3 is linker (n.2). In some variations of formula (33) described in the paragraphs above, L4 is linker (n.2). In some variations of formula (33) described in the paragraphs above, LI and L2 are linker (n.2). In some variations of formula (33) described in the paragraphs above, LI and L3 are linker (n.2). In some variations of formula (33) described in the paragraphs above, LI and L4 are linker (n.2). In some vari ations of formula (33) described in the paragraphs above, L2 and L3 are linker (n.2). In some variations of formula (33) described in the paragraphs above, L2 and L4 are linker (n.2). In some variations of formula (33) described in the paragraphs above, L3 and L4 are linker (n.2). In some variations of formula (33) described in the paragraphs above, LI, L2, and L3 are linker in.2) In some variations of formula (33) described in the paragraphs above, LI, L2, and L4 are linker (n.2). In some variations of formula (33) described in the paragraphs above, LI, L3, and L4 are linker (n.2). In some variations of formula (33) described in the paragraphs above, L2, L3, and L4 are linker (n.2). In some variations of formula (33) described in the paragraphs above, LI, L2, L3, and L4 are linker (n.2).
[1001] In some variations of formula (33) described in the paragraphs above, at least one of LI, L2, L3, and L4 is linker (o):
Figure imgf000311_0001
' , in which in which « is 0-5, «2 is 1-5, n3 is 0-5, and * is the attachment site for the cationic dye moiety D.
[1002] In some variations of formula (33) in which at least one of LI, L2, L3, and L4 is linker (o), «i is 0-5, 0-4, 0-3, 0-2, 0-1 , 1 -5, 1-4, 1 -3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1 , 2, 3, 4, or 5.
[1003] In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (o), n2 is 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2,
3, 4, or 5,
[1004] In some variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (o), n3 is 0-5, 0-4, 0-3, 0-2, 0-1, 1-5, 1 -4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1, 2, 3, 4, or 5.
[1005] In some variations of formula (33) described in the paragraphs above, LI is linker (o). In some variations of formula (33) described in the paragraphs above, L2 is linker (o). In some variations of formula (33) described in the paragraphs above, L3 is linker (o). In some variations of formula (33) described in the paragraphs above, L4 is linker (o). In some variations of formula (33) described in the paragraphs above, LI and L2 are linker (o). In some variations of formula (33) described in the paragraphs above, LI and L3 are linker (o). In some variations of formula (33) described in the paragraphs above, LI and L4 are linker (o). In some variations of formula (33) described in the paragraphs above, L2 and L3 are linker (o). In some variations of formula (33) described in the paragraphs above, L2 and L4 are linker (o). In some variations of formula (33) described in the paragraphs above, L3 and L4 are linker (o). In some variations of formula (33) described in the paragraphs above, LI, L2, and L3 are linker (o). In some variations of formula (33) described in the paragraphs above, LI, L2, and L4 are linker (o). In some variations of formula (33) described in the paragraphs above, LI, L3, and L4 are linker (o). In some variations of formula (33) described in the paragraphs above, L2, L3, and L4 are linker (o). In some variations of formula (33) described in the paragraphs above, LI, L2, L3, and L4 are linker (o).
[1006] In some variations of formula (33) described in the paragraphs above, at least one of LI, L2, L3, and L4 is linker (p):
Figure imgf000312_0001
(P) , in which tti is 0-5, «2 is 1-5, n3 is 0-5, and * is the attachment site for the cationic dye moiety D. f 1007] In some variations of formula (33) described above in which at least one of LI, L2, L3, and L4 is linker (p), is 0-5, 0-4, 0-3, 0-2, 0-1, 1 -5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1 , 2, 3, 4, or 5.
[1008] In some variations of formula (33) described above in which at least one of LI, L2, L3, and L4 is linker (p), n2 is 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5.
[1009] In some variations of formula (33) described above in which at least one of LI, L2, L3, and L4 is linker (p), n3 is 0-5, 0-4, 0-3, 0-2, 0-1, 1-5, 1 -4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1, 2, 3, 4, or 5.
11010] In some variations of formula (33) described in the paragraphs above, LI is linker (p). In some variations of formula (33) described in the paragraphs above, L2 is linker (p). In some variations of formula (33) described in the paragraphs above, L3 is linker (p). In some variations of formula (33) described in the paragraphs above, L4 is linker (p). In some variations of formula (33) described in the paragraphs above, LI and L2 are linker (p). In some variations of formula (33) described in the paragraphs above, LI and L3 are linker (p). In some variations of formula
11 1 (33) described in the paragraphs above, LI and L4 are linker (p). In some variations of formula (33) described in the paragraphs above, L2 and L3 are linker (p). In some variations of formula (33) described in the paragraphs above, L2 and L4 are linker (p). In some variations of formula (33) described in the paragraphs above, L3 and L4 are linker (p). In some variations of formula (33) described in the paragraphs above, LI, L2, and L3 are linker (p). In some variations of formula (33) described in the paragraphs above, LI, L2, and L4 are linker (p). In some variations of formula (33) described in the paragraphs above, LI, L3, and L4 are linker (p). In some variations of formula (33) described in the paragraphs above, L2, L3, and L4 are linker (p). In some variations of formula (33) described in the paragraphs above, LI, L2, L3, and L4 are linker (Ρ)·
[1011] In some variations of formula (33) described in the paragraphs above, at least one of LI, L2, L3, and L4 is linker (q):
Figure imgf000313_0001
in which ¾</ is 0-5, ¾ is 1 -5, and * is the attachment site for the cationic dye moiety
[1012] In some variations of formula (33) in which at least one of LI, L2, L3, and L4 is linker (o), n4 is 0-5, 0-4, 0-3, 0-2, 0-1, 1-5, 1 -4, 1-3, 1 -2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1, 2, 3, 4, or 5.
[1013] In some variations of formula (33) described above in which at least one of LI, L2, L3, and L4 is linker (q), n2 is 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5.
[1014] In some variations of formula (33) described in the paragraphs above, LI is linker (q). In some variations of formula (33) described in the paragraphs above, L2 is linker (q). In some variations of formula (33) described in the paragraphs above, L3 is linker (q). In some variations of formula (33) described in the paragraphs above, L4 i s linker (q). In some variati ons of formula (33) described in the paragraphs above, LI and L2 are linker (q). In some variations of formula (33) described in the paragraphs above, LI and L3 are linker (q). In some variations of formula (33) described in the paragraphs above, LI and L4 are linker (q). In some variations of formula (33) described in the paragraphs above, L2 and L3 are linker (q). In some variations of formula (33) described in the paragraphs above, L2 and L4 are linker (q). In some variations of formula (33) described in the paragraphs above, L3 and L4 are linker (q). In some variations of formula (33) described in the paragraphs above, LI, L2, and L3 are linker (q). In some variations of formula (33) described in the paragraphs above, LI, L2, and L4 are linker (q). In some variations of formul a (33) described in the paragraphs above, LI, L3, and L4 are linker (q). In some variations of formula (33) described in the paragraphs above, L2, L3, and L4 are linker (q). In some vari ations of formula (33) described in the paragraphs above, LI, L2, L3, and L4 are linker
(q)-
[1015] In some variations of formula (33) described in the paragraphs above, at least one of LI, L2, L3, and L4 is linker (r):
Figure imgf000314_0001
(r) , in which ni is 0-5, «2 is 1 -5, n3 is 0-5, and * is the attachment site for the cationic dye moiety D.
[1016] In some of variations of formula (33) in which at least one of LI, L2, L3, and L4 is linker (r), m is 0-5, 0-4, 0-3, 0-2, 0-1 , 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1 , 2, 3, 4, or 5.
[1017] In some of variations of formula (33) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (r), n2 is 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5,
[1018] In some of variations of formula (33) in which at least one of LI, L2, L3, and L4 is linker (r), n3 is 0-5, 0-4, 0-3, 0-2, 0-1, 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1, 2, 3, 4, or 5,
[1019] In some variations of formula (33) described in the paragraphs above, LI is linker (r). In some variations of formula (33) described in the paragraphs above, L2 is linker (r). In some vari ations of formula (33) described in the paragraphs above, L3 is linker (r). In some vari ations of formula (33) described in the paragraphs above, L4 is linker (r). In some variations of formula (33) described in the paragraphs above, LI and L2 are linker (r). In some vari ations of formula (33) described in the paragraphs above, LI and L3 are linker (r). In some variations of formula (33) described in the paragraphs above, LI and L4 are linker (r). In some variations of formula (33) described in the paragraphs above, L2 and L3 are linker (r). In some variations of formula
J 1 (33) described in the paragraphs above, L2 and L4 are linker (r). In some variations of formula (33) described in the paragraphs above, L3 and L4 are linker (r). In some variations of formula (33) described in the paragraphs above, LI, L2, and L3 are linker (r). In some variations of formula (33) described in the paragraphs above, LI, L2, and L4 are linker (r). In some variations of formula (33) described in the paragraphs above, LI, L3, and L4 are linker (r). In some variations of formula (33) described in the paragraphs above, L2, L3, and L4 are linker (r). In some variations of formula (33) described in the paragraphs above, LI, L2, L3, and L4 are linker (r).
[1020] In some variations of formula (33) described in the paragraphs above, at least one of LI, L2, L3, and L4 is linker (s):
Figure imgf000315_0001
, in which n} is 0-5, n2 is 1-5, n:i is 0-5, and * is the attachment site for the cationic dye moiety D.
[1021] In some variations of formula (33) described in the paragraphs above, LI is linker (s). In some variations of formula (33) described in the paragraphs above, L2 is linker (s). In some variations of formula (33) described in the paragraphs above, L3 is linker (s). In some variations of formula (33) described in the paragraphs above, L4 is linker (s). In some variations of formula (33) described in the paragraphs above, LI and L2 are linker (s). In some variations of formula (33) described in the paragraphs above, LI and L3 are linker (s). In some variations of formula (33) described in the paragraphs above, LI and L4 are linker (s). In some variations of formula (33) described in the paragraphs above, L2 and L3 are linker (s). In some variations of formula (33) described in the paragraphs above, L2 and L4 are linker (s). In some variations of formula (33) described in the paragraphs above, L3 and L4 are linker (s). In some variations of formula (33) described in the paragraphs above, LI, L2, and L3 are linker (s). In some variations of formula (33) described in the paragraphs above, LI, L2, and L4 are linker (s). In some variations of formula (33) described in the paragraphs above, LI, L3, and L4 are linker (s). In some variations of formula (33) described in the paragraphs above, L2, L3, and L4 are linker (s). In some variations of formula (33) described in the paragraphs above, LI, L2, L3, and L4 are linker (si f 1022] In some variations of formula (33) described in the paragraphs above, LI is absent. In some variations of formula (33) described in the paragraphs above, L2 is absent. In some variations of formula (33) described in the paragraphs above, L3 is absent. In some variations of formula (33) described in the paragraphs above, L4 is absent. In some variations of formula (33) described in the paragraphs above, LI and L2 are absent. In some variations of formula (33) described in the paragraphs above, LI and L3 are absent. In some variations of formula (33) described in the paragraphs above, LI and L4 are absent. In some variations of formula (33) described in the paragraphs above, L2 and L3 are absent. In some variations of formula (33) described in the paragraphs above, L2 and L4 are absent. In some variations of formula (33) described in the paragraphs above, L3 and L4 are absent. In some variations of formula (33) described in the paragraphs above, LI, L2, and L3 are absent. In some vari ations of formula (33) described in the paragraphs above, LI, L2, and L4 are absent. In some variations of formula (33) described in the paragraphs above, LI, L3, and L4 are absent. In some variations of formula (33) described in the paragraphs above, L2, L3, and L4 are absent. In some variations of formula (33) described in the paragraphs above, LI, L2, L3, and L4 are absent.
[1023] In some variations of formula (33), each of LI, L2, L3, and L4 is a different linker. In some variations of formula (33), each of LI, L2, L3, and L4 is the same linker. In some variations of formula (33), LI is a first linker and each of L2, L3, and L4 is the same second linker, wherein the first and second linkers are different. In some variations of formula (33), L2 is a first linker, and each of LI, L3, and L4 is a second linker, wherein the first and second linkers are different. In some variations of formula (33), L3 is a first linker, and each of LI, L2, and L4 is a second linker, wherein the first and second linkers are different. In some variations of formula (33), L4 is a first linker, and each of LI, L2, and L3 is a second linker, wherein the first and second linkers are different. In some variations of formula (33), each of LI and L2 is the same first linker, and each of L3 and L4 is the same second linker, wherein the first and second linkers are different. In some variations of formula (33), each of LI and L2 is the same first linker, L3 is a second linker, and L4 is a third linker, wherein the first, second, and third linkers are different. In some variations of formula (33), each of LI and L3 is the same first linker, and each of L2 and L4 is the same second linker, wherein the first and second linkers are different. In some variations of formula (33), each of LI and L3 is the same first linker, L2 is a second linker, and L4 is a third linker, wherein the first, second, and third linkers are different. In some variations of formula (33), each of LI and L4 is the same first linker, and each of L2 and L3 is the same second linker, wherein the first and second linkers are different. In some variations of formula (33), each of LI and L4 is the same first linker, L2 is a different second linker, and L3 is a different third linker, wherein the first, second, and third linkers are different. In some variations of formula (33), each ofL2 and L3 is the same first linker, and each of LI and L4 is the same second linker, wherein the first and second linkers are different.
[1024] In some variations of formula (33) described in the paragraphs above, Dl is safranin-O. In some variations of formula (33) described in the paragraphs above, D2 is safranin-O. In some variations of formula (33) descri bed in the paragraphs above, D3 i s safranin-O. In some variations of formula (33) described in the paragraphs above, D4 is safranin-O. In some variations of formula (33) described in the paragraphs above, Dl and D2 are safranin-O. In some variations of formula (33) described in the paragraphs above, Dl and D3 are safranin-O. In some variations of formula (33) descri bed in the paragraphs above, Dl and D4 are safranin-O. In some variations of formula (33) described in the paragraphs above, D2 and D3 are safranin-O. In some variations of formula (33) described in the paragraphs above, D2 and D4 are safranin-O. In some variations of formula (33) described in the paragraphs above, D3 and D4 are safranin-O. In some variations of formula (33) described in the paragraphs above, Dl, D2, and D3 are safranin-O. In some variations of formula (33) described in the paragraphs above, Dl, D2, and D4 are safranin- O. In some variations of formula (33) described in the paragraphs above, Dl, D3, and D4 are safranin-O. In some variations of formula (33) described in the paragraphs above, D2, D3, and D4 are safranin-O. In some variations of formula (33) described in the paragraphs above, Dl, D2, D3, and D4 are safranin-O.
[1025] In some variations of formula (33) described in the paragraph above, the pendant phenyl ring of Dl is unsubstituted. In some variati ons of formula (33) described in the paragraph above, the pendant phenyl ring of Dl is substituted with 1-3 (e.g., 1-3, 1 -2, 1, 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring ofDl is substituted, the substituents are selected independently from— H2,— HR,— NR2,— OH,— O",
NHCOCI k,— -NHCOR, OCj h OR, --C2H5,—R, and (\j k wherein R is C1-C6 linear or branched alkyl (e.g., C1-C6, C 1-C5, C1-C4, C 1-C3, C 1-C2, C I, C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— -N02,— -N 3 +, halo (e.g., F, Br, CI, I), trihalide (e.g., ---CF3, CCk --CBr3, Ch i.— CN, - -SO3H, --CQOH,— COOR,—CHO, and — COR, wherein R is C1-C6 linear or branched alkyl (e.g., C 1 -C6, C 1-C5, C 1 -C4, C 1-C3, Cl- C2, CI , C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-
C6, C5, or C6 linear or branched alkyl).
[1026] In some variations of formula (33) described in the two paragraphs above, the pendant phenyl ring of D2 is unsubstituted. In some variations of formula (33) described in the paragraph above, the pendant phenyl ring of D2 is substituted with 1 -3 (e.g., 1 -3, 1-2, 1 , 2, or 3) electron- donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— -NH2,— NHR,— NR2,— OH,— O",
— NHCOCH3,— NHCOR,— OCH3,—OR,— C2H5,— R, and— C6¾, wherein R is C 1-C6 linear or branched alkyl (e.g., C 1-C6, C 1-C5, C1-C4, C 1-C3, C1-C2, CI , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl ). In some embodiments in which the pendant phenyl ring of 1)2 is substituted, the substituents are selected independently from— -NO2,— - R3 +, halo (e.g., F, Br, CI, I), trihaiide (e.g.,— CF3,— CCI3,— CBr3,— CI3),— CN,— SO3H,— COOH,— COOR,— CHO, and — COR, wherein R is C1-C6 linear or branched alkyl (e.g., C 1 -C6, C 1-C5, C1 -C4, C 1-C3, C l- C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
[1027] In some variations of formula (33) described in the three paragraphs above, the pendant phenyl ring of D3 is unsubstituted. In some variations of formula (33) described in the paragraph above, the pendant phenyl ring of D3 is substituted with 1-3 (e.g., 1-3, 1-2, 1, 2, or 3) electron- donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of D3 is substituted, the substituents are selected independently from— NH2,— NHR,— NR2,— OH,— O",
— NHCOCH3,— -NHCOR, --OCH3,—OR, --C2H5,—R, and C,,l k wherein R is C1-C6 linear or branched alkyl (e.g., C1-C6, C 1-C5, C1-C4, C 1-C3, C1-C2, C I , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched aikyi). In some embodiments in which the pendant phenyl ring of D3 is substituted, the substituents are selected independently from— -N02,— -NR3 +, halo (e.g., F, Br, CI, I), trihaiide (e.g.,— CF3,— CCI3,— CBr3,— CI3),— CN,— SO3H, -—COOH,— COOR,—CHO, and — COR, wherein R is C1.-C6 linear or branched al kyl (e.g., C I -C6, C1-C5, C I -C4, C 1 -C3, C l- C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl). [1028] In some variations of formula (33) described in the three paragraphs above, the pendant phenyl ring of D4 is unsubstituted. In some variations of formula (33) described in the paragraph above, the pendant phenyl ring of D4 is substituted with 1 -3 (e.g., 1 -3, 1-2, 1 , 2, or 3) electron- donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of D4 is substituted, the substituents are selected independently from— -NH2,— NHR,— NR2,— OH,— O",
— ICOCH3,— NHCOR,— OCH3,—OR,— C2H5,— R, and C-j k wherein R is C 1-C6 linear or branched alky! (e.g., C 1-C6, C 1-C5, C1-C4, C 1-C3, C1-C2, CI , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of 1)4 is substituted, the substituents are selected independently from— 02,— R3 , halo (e.g., F, Br, CI, I), trihaiide (e.g., --CF3, --CCI3, ---CBr3, --CI3), --CN, SO : I L --COOH, --COOR, --CHO, and — COR, wherein R is C1-C6 linear or branched alkyl (e.g., C 1 -C6, C 1-C5, C1 -C4, C 1-C3, C l- C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
[1029] In some variations, cationic dye multimers are cyclic, as illustrated by formula (34):
Figure imgf000319_0001
, wherein at least one of Dl, D2, and D3 is a cationic dye moiety and one or more of LI, L2, and L3 are absent or each of LI, L2, and L3 is a linker independently selected from linker (a. l), linker (a.2), linker (b. l), linker (c. l), linker (c.2), linker (d), linker (e. 1), linker (f.1), linker (f.2), linker (g.1), linker (g.2), linker (h. 1), linker (h.2), linker (i. l), linker (i.2), linker (j . ), linker (j .2), linker (k), linker (1.1 ), linker (1.2), is linker (m. l ), linker (n. l ), linker (n.2), linker (o), linker (p), linker (q), linker (r), and linker (s), described above. [1030] In some variations of formula (34) described in the paragraphs above, at least one of Dl, D2, and D3 is a different cationic dye moiety. In some variations of formula (34) described in the paragraphs above, at least one of Dl, D2, and D3 is the same cationic dye moiety. In some variations of formula (34) described in the paragraphs above, at least one of Dl and D2 is the same first cationic dye moiety and D3 is a second cationic dye moiety, wherein the first and second catiomc dye moieties are different. In some variations of formula (34) described in the paragraphs above, at least one of Dl and D3 is the same first catiomc dye moiety and D2 is a second cationic dye moiety, wherein the first and second cationic dye moieties are different. In some variations of formula (34) described in the paragraphs above, at least one of D2 and D3 is the same first cationic dye moiety and Dl is a second catiomc dye moiety, wherein the first and second catiomc dye moieties are different.
[1031] In some variations of formula (34) described in the paragraphs above, at least one of Dl, D2, and D3 is independently are selected from the group consisting of safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue.
[1032] In some variations of formula (34) described in the paragraphs above, at least one of LI, L2, and L3 is linker (a.1):
Figure imgf000320_0001
(a.1 ) , in which n is 1-6, n1 is 1-4, and * is the attachment site for the cationic dye moiety D.
[1033] In some variations of formula (34) in which at least one of LI, L2, and L3 is linker (a.1), n is 1 -6, 1-5, 1-4, 1-3, 1-2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, 5-6, 1, 2, 3, 4, 5, or 6.
[1034] In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (a. l), m is 1-4, 1-3, 1-2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[1035] In some variations of formula (34) described in the paragraphs above, LI is linker (a. l). In some variations of formula (34) described in the paragraphs above, L2 is linker (a. l). In some variations of formula (34) described in the paragraphs above, L3 is linker (a. l). In some variations of formula (34) described in the paragraphs above, LI and L2 are linker (a. l). In some variations of formula (34) described in the paragraphs above, LI and L3 are linker (a. l). In some variations of formula (34) described in the paragraphs above, L2 and L3 are linker (a. l). In some variations of formula (34) described in the paragraphs above, LI, L2, and L3 are linker (a. l ). [1036] In some variations of formula (34) described in the paragraphs above, at least one of LI, L2, and L3 is linker (a.2):
Figure imgf000321_0001
, in which n is 1-6, tii is 1-4, and * is the attachment site for the cationic dye moiety D.
11037] In some variations of formula (34) in which at least one of LI, L2, and L3 is linker (a.2), n i s 1 -6, 1-5, 1-4, 1-3, 1-2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, 5-6, 1, 2, 3, 4, 5, or 6.
[1038] In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (a.2), n} is 1-4, 1-3, 1 -2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[1039] In some variations of formula (34) described in the paragraphs above, LI is linker (a.2). In some variations of formula (34) described in the paragraphs above, L2 is linker (a.2). In some variations of formula (34) descri bed in the paragraphs above, L3 is linker (a.2). In some variations of formula (34) described in the paragraphs above, LI and L2 are linker (a.2). In some variations of formula (34) described in the paragraphs above, LI and L3 are linker (a.2). In some variations of formula (34) described in the paragraphs above, L2 and L3 are linker (a.2). In some variations of formula (34) described in the paragraphs above, LI, L2, and L3 are linker (a.2).
[1040] In some variations of formula (34) described in the paragraphs above, at least one of LI, L2, and L3 is linker (b. l):
Figure imgf000321_0002
, in which n is 0-6, ttj is 1-4, and * is the attachment site for the cationic dye moiety D.
[1041] In some variations of formula (34) in which at least one of LI, L2, and L3 is linker (b.1), n i s 0-6, 0-5, 0-4, 0-3, 0-2, 0-1, 1-6, 1 -5, 1-4, 1 -3, 1-2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, 5-6, 0, 1, 2, 3, 4, 5, or 6.
[1042] In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (b. l), «, is 1-4, 1-3, 1-2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[1043] In some variations of formula (34) described in the paragraphs above, at least one of LI, L2, and L3 is linker c. l ): (°·^ , in which n is 0-6, nj is 1-4, either (1) Ra and Rj, independently are H or CH3
O
or (2) Ra and Rb are ""^ or '¾ or (3) two of C aRb are , and * is the attachment site for the cationic dye moiety D.
[1044] In some variations of formula (34) in which at least one of LI, L2, and L3 is linker (c. 1), n is 0-6, 0-5, 0-4, 0-3, 0-2, 0-1, 1-6, 1 -5, 1-4, 1 -3, 1-2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, 5-6, 0, 1, 2, 3, 4, 5, or 6,
[1045] In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (c. l), m is 1-4, 1-3, 1-2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[1046] In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (c. I), Ra is H and Rj, is H. In some variations of formula (34) described in the paragraphs above in which at least one of LI , L2, and L3 i s linker (c. l), Ra is H and Rb is CH3. In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (c. 1 ), Ra and I¾> are " w¾ . In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (c. l), Ra
O
and ¾ are . In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (c. l), two of CRaRb are
[1047] In some variations of formula (34) described in the paragraphs above, LI i s linker (c. l). In some variations of formula (34) described in the paragraphs above, L2 is linker (c. l). In some variations of formula (34) described in the paragraphs above, L3 is linker (c. l). In some variations of formula (34) described in the paragraphs above, LI and L2 are linker (c. l). In some variations of formula (34) described in the paragraphs above, LI and L3 are linker (c. l ). In some variations of formula (34) described in the paragraphs above, L2 and L3 are linker (c. l ). In some variations of formula (34) described in the paragraphs above, LI, L2, and L3 are linker (c. l).
8] In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (c. l), L is
Figure imgf000323_0001
[1049] In some variations of formula (34) described in the paragraphs above, LI is linker (c. l). In some variations of formula (34) described in the paragraphs above, L2 is linker (c. l). In some variations of formula (34) described in the paragraphs above, L3 is linker (c. l ). In some variations of formula (34) described in the paragraphs above, LI and L2 are linker (c. l). In some variations of formula (34) described in the paragraphs above, LI and L3 are linker (c. l ). In some variations of formula (34) described in the paragraphs above, L2 and L3 are linker (c. l). In some variations of formula (34) described in the paragraphs above, LI, L2, and L3 are linker (c.1).
[1050] In some variations of formula (34) described in the paragraphs above, at least one of LI, L2, and L3 is linker (c.2):
Figure imgf000323_0002
site for the cationic dye moiety D.
[1051] In some variations of formula (34) in which at least one of LI, L2, and L3 is linker (c.2), n is 0-6, 0-5, 0-4, 0-3, 0-2, 0-1, 1-6, 1-5, 1-4, 1-3, 1-2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, 5-6, 0, 1, 2, 3, 4, 5, or 6.
[1052] In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (c.2), «; is 1-4, 1 -3, 1-2, 2-4, 2-3, 3-4, 1, 2, 3, or 4. [1053] In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (c.2), Ra is H and Rj, is H. In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (c.2), Ra is H and ¾ is CH3. In some variations of formula (34) descri in the paragraphs above in which at least one of LI, L2, and L3 is linker (c.2), Ra and are
Figure imgf000324_0001
. In some variations of formula
(34) described in the paragraphs above in which at least one of L I, L2, and L3 is linker (c.2), and Rjj are '¾ ^\ in some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (c.2), two of CRaRb are .
[1054] In some variations of formula (34) described in the paragraphs above, LI is linker (b. l). In some variations of formula (34) described in the paragraphs above, L2 is linker (b. l). In some variations of formula (34) described in the paragraphs above, L3 is linker (b. l). In some variations of formula (34) described in the paragraphs above, LI and L2 are linker (b. l). In some variations of formula (34) described in the paragraphs above, LI and L3 are linker (b. l). In some variations of formula (34) described in the paragraphs above, L2 and L3 are linker (b. l ). In some variations of formula (34) described in the paragraphs above, LI, L2, and L3 are linker (b. l).
[1055] In some variations of formula (34) described in the paragraphs above in which at least one of LI L2, and L3 is linker c
Figure imgf000324_0002
56] In some variations of formula (34) described in the paragraphs above, LI is linker (c.2). In some variations of formula (34) described in the paragraphs above, L2 is linker (c.2). In some variations of formula (34) described in the paragraphs above, L3 is linker (c.2). In some variations of formula (34) described in the paragraphs above, LI and L2 are linker (c.2). In some variations of formula (34) described in the paragraphs above, LI and L3 are linker (c .2). In some variations of formula (34) described in the paragraphs above, L2 and L3 are linker (c.2). In some variations of formula (34) described in the paragraphs above, LI, L2, and L3 are linker (c.2).
[1057] In some variations of formula (34) described in the paragraphs above, at least one of LI , L2, and L3 is linker (d):
Figure imgf000325_0001
(d) -10, (1) Ra and R independently are H or CH3, or (2) Ra and Rb are
Figure imgf000325_0002
dye moiety D
[1058] In some variations of formula (34) in which at least one of LI, L2, and L3 is linker (d), k is 2-10, 2-9, 2-8, 2-7, 2-6, 2-5, 2-4, 2-3, 3-10, 3-9, 3-8, 3-7, 3-6, 3-5, 3-4, 4- 10, 4-9, 4-8, 4-7, 4-6, 4-5, 5-10, 5-9, 5-8, 5-7, 5-6, 6-10, 6-9, 6-8, 6-7, 7-10, 7-9, 7-8, 8-10, 8-9, 9-10, 2, 3, 4, 5, 6, 7, 8, 9, or 10.
[1059] In some variations of formula (34) described in the paragraphs above in which at least one of LI , L2, and L3 is linker (d), Ra is H and b is II In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (d), Ra is H and is CH3. In some variations of formula (34) described in the paragraphs above in which at
: one of Li, L2, and L3 is linker (d), Ra and are " L . In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (d), Ra and O
are "¾ . In some variations of formula (34) described in the paragraphs above in which at least one of LI, L.2, and L3 is linker (d), two of CRaRb are 1.
In some variations of formula (34) described in the paragraphs above, LI is linker (d). In some variations of formula (34) described in the paragraphs above, L2 is linker (d). In some variations of formula (34) described in the paragraphs above, L3 is linker (d). In some variations of formula (34) described in the paragraphs above, LI and L2 are linker (d). In some variations of formula (34) described in the paragraphs above, LI and L3 are linker (d). In some variations of formula (34) described in the paragraphs above, L2 and L3 are linker (d). In some variations of formula (34) described in the paragraphs above, LI, L2, and L3 are linker (d).
[1061] In some variations of formula (34) described in the paragraphs above, at least one of LI, L2, and L3 is linker (e):
Figure imgf000326_0001
(e.1 )
, in which n is 0-6, n} is 1-4, and * is the attachment site for the cationic dye moiety D.
[1062] In some variations of formula (34) in which at least one of L I, L2, and L3 i s linker (e. l), n is 0-6, 0-5, 0-4, 0-3, 0-2, 0-1 , 1-6, 1-5, 1 -4, 1-3, 1 -2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, 5-6, 0, 1, 2, 3, 4, 5, or 6.
[1063] In some variations of formula (34) described in the paragraphs above in which at least one of LI, L.2, and L3 is linker (e. l ), n} is 1 -4, 1-3, 1 -2, 2-4, 2-3, 3-4, 1 , 2, 3, or 4.
[1064] In some variations of formula (34) described in the paragraphs above, LI is linker (e. l ). In some variations of formula (34) described in the paragraphs above, L2 is linker (e. l). In some variations of formula (34) descri bed in the paragraphs above, L3 is linker (e. l ). In some variations of formula (34) described in the paragraphs above, LI and L2 are linker (e. l). In some variations of formula (34) described in the paragraphs above, LI and L3 are linker (e. l). In some variations of formula (34) described in the paragraphs above, L2 and L3 are linker (e. l). In some variations of formula (34) described in the paragraphs above, LI, L2, and L3 are li nker (e. 1 ).
[1065] In some variations of formula (34) described in the paragraphs above, at least one of LI, L2, and L3 is linker (f. l):
Figure imgf000326_0002
, in which nj is 0-5, «? is 1-5, and * is the attachment site for the cationic dye moiety D.
[1066] In some variations of formula (34) in which at least one of LI, L2, and L3 is linker (f. l), HI is 0-5, 0-4, 0-3, 0-2, 0-1 , 1-5, 1-4, 1 -3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1 , 2, 3, 4, or 5. [1067] In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (f. l), n2 is 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5.
[1068] In some variations of formula (34) described in the paragraphs above, LI is linker (f. l). In some variations of formula (34) described in the paragraphs above, L2 is linker (f. l ). In some variations of formula (34) described in the paragraphs above, L3 is linker (f. l). In some variations of formula (34) described in the paragraphs above, LI and L2 are linker (f. l). In some variations of formula (34) described in the paragraphs above, LI and L3 are linker (f.1). In some variations of formula (34) described in the paragraphs above, L2 and L3 are linker (f. 1). In some variations of formula (34) described in the paragraphs above, LI, L2, and L3 are linker (f. l).
[1069] In some variations of formula (34) described in the paragraphs above, at least one of LI, L2, and L3 is linker (f.2):
Figure imgf000327_0001
, in which n} is 0-5, n2 is 1-5, and * is the attachment site for the cationic dye moiety D.
[1070] In some variations of formula (34) in which at least one of LI, L2, and L3 is linker (f.2), it! is 0-5, 0-4, 0-3, 0-2, 0-1 , 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1 , 2, 3, 4, or 5.
[1071] In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (f.2), n2 is 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5.
[1072] In some variati ons of formul a (34) described in the paragraphs above, LI i s linker (f.2). In some variations of formula (34) described in the paragraphs above, L2 is linker (f.2). In some variations of formula (34) described in the paragraphs above, L3 is linker (f.2). In some variations of formula (34) described in the paragraphs above, LI and L2 are linker (f.2). In some variations of formula (34) described in the paragraphs above, LI and L3 are linker (f.2). In some variations of formula (34) described in the paragraphs above, L2 and L3 are linker (f.2). In some variations of formula (34) described in the paragraphs above, LI, L2, and L3 are linker (f.2).
[1073] In some variations of formula (34) described in the paragraphs above, at least one of LI, L2, and L3 is linker (g.1):
Figure imgf000328_0001
(g-1 ) , in which n} is 0-5, n2 is 1-5, and * is the attachment site for the cationic dye moiety I),
[1074] In some variations of formula (34) in which at least one of LI , L2, and L3 is linker (g. l), ni is 0-5, 0-4, 0-3, 0-2, 0-1, 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1, 2, 3, 4, or 5.
[1075] In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (g. l), n2 is 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1 , 2, 3,
4, or 5.
[1076] In some variations of formula (34) described in the paragraphs above, LI is linker (g. l). In some variations of formula (34) described in the paragraphs above, L2 is linker (g. l). In some variations of formula (34) described in the paragraphs above, L3 is linker (g. l). In some variations of formula (34) described in the paragraphs above, LI and L2 are linker (g. l). In some variations of formula (34) described in the paragraphs above, LI and L3 are linker (g. l). In some variations of formula (34) described in the paragraphs above, L2 and L3 are linker (g. l). In some variations of formula (34) described in the paragraphs above, LI, L2, and L3 are linker (g. l).
[1077] In some variations of formula (34) described in the paragraphs above, at least one of LI, L2, and L3 is linker (g.2):
Figure imgf000328_0002
(g.2) , in which « is 0-5, « is 1-5, and * is the attachment site for the cationic dye moiety D.
[1078] In some variations of formula (34) in which at least one of LI, L2, and L3 is linker (g.2), it! is 0-5, 0-4, 0-3, 0-2, 0-1 , 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1 , 2, 3, 4, or 5. [1079] In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (g.2), n2 is 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5.
[1080] In some variations of formula (34) described in the paragraphs above, LI is linker (g.2). In some variations of formula (34) described in the paragraphs above, L2 is linker (g.2). In some variations of formula (34) described in the paragraphs above, L3 is linker (g.2). In some variations of formula (34) described in the paragraphs above, LI and L2 are linker (g.2). In some variations of formula (34) described in the paragraphs above, LI and L3 are linker (g.2). In some variations of formula (34) described in the paragraphs above, L2 and L3 are linker (g.2). In some variations of formula (34) described in the paragraphs above, LI, L2, and L3 are linker (g.2).
[1081] In some variations of formula (34) described in the paragraphs above, at least one of LI, L2, and L3 is linker (h. l):
Figure imgf000329_0001
(h.1 ) , in which n} is 0-5, n2 is 1-5, and * is the attachment site for the cationic dye moiety D.
[1082] In some variations of formula (34) in which at least one of L I, L2, and L3 is linker (h . l), ft] is 0-5, 0-4, 0-3, 0-2, 0-1, 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, I, 2, 3, 4, or 5.
[1083] In some variations of formula (34) described in the paragraphs above in which at least one of LI , L2, and L3 i s linker (h. l), n2 is 1 -5, 1-4, 1 -3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3,
4, or 5.
[1084] In some variations of formula (34) described in the paragraphs above, LI is linker (h. l). In some variations of formula (34) described in the paragraphs above, L2 is linker (h. l). In some variations of formula (34) described in the paragraphs above, L3 is linker (h. l ). In some variations of formula (34) described in the paragraphs above, LI and L2 are linker (h. l). In some variations of formula (34) described in the paragraphs above, LI and L3 are linker (h. l). In some variations of formula (34) described in the paragraphs above, L2 and L3 are linker (h. l). In some variations of formula (34) described in the paragraphs above, LI, L2, and L3 are linker (h. 1 ). [1085] In some variations of formula (34) described in the paragraphs above, at least one of LI, L2, and L3 is linker (h.2):
Figure imgf000330_0001
[n. ) ^ jn ^γ^ς^ Rl ig Q-53 n2 js i„55 an(j * is†he attachment site for the cationic dye moiety D.
[1086] In some variations of formula (34) in which at least one of L I, L2, and L3 is linker (h.2), ti! is 0-5, 0-4, 0-3, 0-2, 0-1, 1 -5, 1 -4, 1-3, 1 -2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1, 2, 3, 4, or 5.
[1087] In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (h.2), n2 is 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5.
[1088] In some variations of formula (34) described in the paragraphs above, LI is linker (h.2). In some variations of formula (34) described in the paragraphs above, L2 is linker (h.2). In some variations of formula (34) described in the paragraphs above, L3 is linker (h.2). In some variations of formula (34) described in the paragraphs above, LI and L2 are linker (h.2). In some variations of formula (34) described in the paragraphs above, LI and L3 are linker (h.2). In some variations of formula (34) described in the paragraphs above, L2 and L3 are linker (h.2). In some variations of formula (34) described in the paragraphs above, LI, L2, and L3 are linker (h.2).
[1089] In some variations of formula (34) described in the paragraphs above, at least one of LI, L2, and L3 is linker (i. l ):
Figure imgf000330_0002
, in which n} and n2 independently are 1-5 and * is the attachment site for the cationic dye moiety D.
[1090] In some variations of formula (34) described in the paragraphs above, at least one of LI, L2, and L3 is linker (i. l ), m is 1 -5, 1-4, 1 -3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1 , 2, 3, 4, or 5 , [1091] In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (i. l), m is 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5.
[1092] In some variations of formula (34) described in the paragraphs above, LI is linker (i. l). In some variations of formula (34) described in the paragraphs above, L2 is linker (i. l ). In some variations of formula (34) described in the paragraphs above, L3 is linker (i. l). In some variations of formula (34) described in the paragraphs above, LI and L2 are linker (i. l ). In some variations of formula (34) described in the paragraphs above, LI and L3 are linker (i. l). In some variations of formula (34) described in the paragraphs above, L2 and L3 are linker (i . l ). In some variations of formula (34) described in the paragraphs above, LI, L2, and L3 are linker (i. l).
[1093] In some variations of formula (34) described in the paragraphs above, at least one of LI, L2, and L3 is linker (i.2):
Figure imgf000331_0001
, in which nj and n2 independently are 1-5 and * is the attachment site for the cationic dye moiety D.
[1094] In some variations of formula (34) described in the paragraphs above, at least one of LI , L2, and L3 is linker (i,2), m is 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5 ,
[1095] In some variati ons of formul a (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (i.2), m is 1-5, 1 -4, 1-3, 1 -2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5.
[1096] In some variations of formula (34) described in the paragraphs above, LI is linker (i.2). In some variations of formula (34) described in the paragraphs above, L2 is linker (i .2). In some variations of formula (34) described in the paragraphs above, L3 is linker (i.2). In some variations of formula (34) described in the paragraphs above, LI and L2 are linker (i.2). In some variations of formula (34) described in the paragraphs above, LI and L3 are linker (i.2). In some variations of formula (34) described in the paragraphs above, L2 and L3 are linker (i .2). In some variations of formula (34) described in the paragraphs above, LI, L2, and L3 are linker (i.2).
[1097] In some variations of formula (34) described in the paragraphs above, at least one of LI , L2, and L3 is linker (j . l ):
Figure imgf000332_0001
0.1) , in which n2 is 1-5 and * is the attachment site for the cationic dye moiety I),
[1098] In some variations of formula (34) in which at least one of LI, L2, and L3 is linker (j.l), n2 is 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, I, 2, 3, 4, or 5.
[1099] In some variations of formula (34) described in the paragraphs above, LI is linker (j.l). In some variations of formula (34) described in the paragraphs above, L2 is linker (j.l). In some variations of formula (34) described in the paragraphs above, L3 is linker (j.l). In some variations of formula (34) described in the paragraphs above, LI and L2 are linker (j.1). In some variations of formula (34) described in the paragraphs above, LI and L3 are linker (j.l). In some variations of formula (34) described in the paragraphs above, L2 and L3 are linker (j.l). In some variations of formula (34) described in the paragraphs above, LI, L2, and L3 are linker (j.l).
[1100] In some variations of formula (34) described in the paragraphs above, at least one of LI, L2, and L3 is linker (j.2):
Figure imgf000332_0002
0-2) , in which n2 is 1-5 and * is the attachment site for the cationic dye moiety D.
[1101] In some variations of formula (34) in which at least one of LI, L2, and L3 is linker (j.2), n2 is 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5.
[1102] In some variations of formula (34) described in the paragraphs above, LI is linker (j.2). In some variations of formula (34) described in the paragraphs above, L2 is linker (j.2). In some variations of formula (34) described in the paragraphs above, L3 is linker (j .2). In some variations of formula (34) described in the paragraphs above, LI and L2 are linker (j .2). In some variations of formula (34) described in the paragraphs above, LI and L3 are linker (j .2). In some variations of formula (34) described in the paragraphs above, L2 and L3 are linker (j .2). In some variations of formula (34) described in the paragraphs above, LI, L2, and L3 are linker (j .2).
[1103] In some variations of formula (34) described in the paragraphs above, at least one of LI , L2, and L3 is linker (k):
Figure imgf000333_0001
\ ' , in which I} and h independently are 1-4, n is 1 -4; ring A is ar heteroaryl, cycloalkyl, or heterocyclyl; (1) Rai and Rbi independently are H or CH3 or (2) Ra3 and ¾i independentl lvy aarree
Figure imgf000333_0002
; oorr ( (33)) ttwwoo ooff CCRRaaiiRRbbii aarree ; (1 ) A2 and ϊ½
O
independently are H or C¾ or (2) Ra2 and ¾ independently are ¼ "¾■ < o orr ¼ '¾■ ^ ; orr- Π (3) two of CRa2Rb2 are '^- L ; and * is the attachment site for the cai ionic dye moiety D.
[1104] In some variations of formula (34) in which at least one of LI, L2, and 13 is linker (k), lj is 1-4, 1-3, 1-3, 1-2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[1105] In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (k), l2 is 1-4, 1-3, 1-3, 1-2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[1106] In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (k), Ra{ is H and RM is H. In some variations of formula (34) described in the paragraphs above in which at least one of L I, L.2, and L3 is linker (k), Ral is H and j>i is ( I . In some variations of formula (34) described in the paragraphs above in which at least one of LI , L2, and L3 is linker (k), Rai and RJ,J are "¾ In some variations of formula (34) described in the paragraphs above in which at least one of L I , L2, and L3 is linker (k), Ral
O
and Rbi are '¾ . in some variations of formula (34) described in the paragraphs above in which at least one of L I , L2, and L3 is linker (k), two of CRaiRi,i are ^ ^ . [1107] In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (k), is H and ¾2 is H. In some variations of formula (34) described in the paragraphs above in which at least one of L , L2, and L3 is linker (k), Rjg is H and Rj>2 is ( I f ;. In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (k), R^ and Rj,2 are ^■ In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (k), Ra2
O
J . «s
and Rb2 are '¾ . in some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (k), two of C a2Rs>2 are
[1108] In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (k), ring A is
Figure imgf000334_0001
optionally substituted with halo or C1-C6 linear or branched alkyl;
Figure imgf000334_0002
optionally substituted with halo or C1 -C6 linear or branched alkyl; or
Figure imgf000334_0003
J J J
Figure imgf000335_0001
optionally substituted with halo or C 1-C6 linear or branched alkyl.
[1109] In some variations of formula (34) described in the paragraphs above in which L is linker (k), ring A is substituted with halo. In some variations, the halo is F, Br, I, or CI.
[1110] In some variations of formula (34) described in the paragraphs above in which L is linker (k), ring A is substituted with C 1-C6 linear or branched alkyl (e.g., C 1 -C6, C 1-C5, C 1-C4, Cl- C3, C 1-C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl).
[1111] In some variations of formula (34) described in the paragraphs above, LI is linker (k). In some variations of formula (34) described in the paragraphs above, L2 is linker (k). In some variations of formula (34) described in the paragraphs above, L3 is linker (k). In some variations of formula (34) described in the paragraphs above, L Λ and L2 are linker (k). In some variations of formula (34) described in the paragraphs above, I Λ and L3 are linker (k). In some variations of formul a (34) described in the paragraphs above, I .2 and L3 are linker (k). In some variations of formula (34) described in the paragraphs above, I Λ, L2, and L3 are linker (k).
[1112] In some variations of formula (34) described in the paragraphs above, at least one of LI , L2, and L3 is linker (1.1 ):
Figure imgf000336_0001
-1 ^ , in which ¾, l2- , n, Oj, and o2 independently are 1 -4; ring A is aryl, heteroaryl, cycloalkyl, or heterocyclvi; for each independent instance of Rai and
R*i, Rai a d Rbi(l ) independently are H or CI¾, or (2) RAI and M independently are '^- or O
"¾ , or (3) two of CRaiRbi are ¾ ; for each independent instance of Ra2 and R^, Ra2 and
V u
b2 (1) independently are H or CH3, or (2) RA2 and Jlb2 independently are ^ or , or (3) two of CRa2Rj,2 are 'x ; for each independent instance of Rci and ^i, Rci and Rai (1) — y O
independently are H or CH3, or (2) and R^i independently are "^- or "^- or (3) two of ciKui are for each independent instance of c2 and R^, ^ and ¾2 (1)
r— y O
independently are H or CH3, or (2) Rc2 and Rd2 independently are '¾ ^ or '¾- or (3) two of
:2K(i2 are and * is the attachment site for the cationic dye moiety D.
[1113] In some variations of formula (34) in which at least one of L I, L2, and L3 is linker (1. 1), // is 1-4, 1-3, 1-3, 1-2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[1114] In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (1.1), l2 is 1-4, 1-3, 1-3, 1-2, 2-4, 2-3, 3-4, 1, 2, 3, or 4. [I I 1.5] In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (1.1), Oj is 1-4, 1-3, 1-3, 1-2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[1116] In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (1.1), o2 is 1-4, 1-3, 1-3, 1-2, 2-4, 2-3, 3-4, 1 , 2, 3, or 4,
[1117] In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (1.1), Rai is H and R¾i is H. In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (1.1), Rai is H and Rbi is CH3. In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (1.1), Ra} and RM are "¾ . In some variations of formula (34) described in the paragraphs above in which at least one of LI , L2, and L3 is linker (1. 1 ), Rai
O
and Rbi are '¾ *" . In some variations of formula (34) described in the paragraphs above in which at least one of L 1 , L2, and L3 is linker (1.1 ), two of CRajRbi are ^ ^
[1118] In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (1.1), Ra2 is H and ¾2 is H. In some variations of formula (34) described in the paragraphs above in which at least one of LI , L2, and L3 i s linker (1.1), Ra2 is H and Rj,2 is CH3. In some variations of formula (34) described in the paragraphs above in which at least one of LI , L2, and L3 is linker (1.1 ), Ra2 and Κ¾2 are "^- . In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 i s linker (1.1), Ra2
Figure imgf000337_0001
variations of formula (34) described in the paragraphs above in which at least one of L I , L2, and L3 is linker (1. 1), two of C ^RM are ^ ^i
[1119] In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.1), cS is H and
Figure imgf000337_0002
is H. In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.1), ci is H and R^i is C¾. In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.1), ^ and ^i are " . In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, L3, 9
and L4 is linker (1. 1), ^ and i are In some variations ot formula (34) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1. 1 ), two of CRciRdi are
[1120] In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.1), is H and ^a is H. In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.1), Re? is H and is CH3. In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.1), and are " w¾ . In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, L3,
0
and L4 is linker (1.1), Rc2 and ϊ½ are '¾ ^ \ In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.1), two of CRc2Rd2 are
[1121] In some variations of formula (34) described in the paragraphs above in which at least one of LI , L2, and L3 i s linker (1.1), ring A is
Figure imgf000338_0001
optionally substituted with halo or C1 -C6 linear or branched alkyl;
Figure imgf000338_0002
optionally substituted with halo or C1 -C6 linear or branched alkyl; or
Figure imgf000338_0003
Figure imgf000339_0001
optionally substituted with halo or C1-C6 linear or branched alky
[1122] In some variations of formula (34) described in the paragraphs above in which L is linker (1.1), riiig A is substituted with halo. In some variations, the halo is F, Br, I, or CI. [1123] In some variations of formula (34) described in the paragraphs above in which L is linker (1.1), ring A is substituted with C 1-C6 linear or branched alkyl (e.g. , C 1-C6, C 1-C5, C 1-C4, Cl- C3, C 1-C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl).
[1124] In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (1.1), n is 1 -4, 1-3, 1 -3, 1-2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[1125] In some variations of formula (34) described in the paragraphs above, LI is linker (1.1). In some variations of formula (34) described in the paragraphs above, L2 is linker (1.1). In some variations of formula (34) descri bed in the paragraphs above, L3 is linker (1, 1 ). In some variations of formula (34) described in the paragraphs above, LI and L2 are linker (1. 1). In some variations of formula (34) described in the paragraphs above, LI and L3 are linker (1.1). In some variations of formula (34) described in the paragraphs above, L2 and L3 are linker (1.1). In some variations of formula (34) described in the paragraphs above, LI, L2, and L3 are linker (1, 1).
[1126] In some variations of formula (34) described in the paragraphs above, at least one of LI, L2, and L3 is linker (1.2):
Figure imgf000340_0001
!-L^ , in which lj, l2, n, o and o2 independently are 1-4;
A is aryl, heteroaryl, cycloalkyl, or heterocyclyl; for each independent instance of ai and
Rbi; Rai and R&i(l) independently are H or CH3, or (2) Rai and RM independently are
Figure imgf000340_0002
or
O
, or (3) two of CRaiRbi are for each independent instance of Ra2 and Rj,2, a2 and
Rj,2 ( 1 ) independently are H or CH3, or (2) Ra2 and Rj,2 independently are
Figure imgf000340_0003
or (3) two of CRa2 b2 are for each independent instance of ci and R<n, Rci and
O
independently are H or CH3, or (2) Rci and di independently are ¾ '¾ ^ o orr *"* or (3) two of
C¾iRdi are ¼^£ - for each independent instance of R^ and Rd2, Rc2 and ^? ( Q independently are H or CH3, or (2) Rc2 and ¾2 independently are '¾ ^ or "¾ or (3) two of CE-c2Rd2 are ; and * is the attachment site for the cationic dye moiety D.
11127] In some variations of formula (34) in which at least one of LI, L2, and L3 is linker (1.2), // is 1-4, 1-3, 1-3, 1-2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[1128] In some variations of formula (34) described in the paragraphs above in which at least one of LI, 1,2, and L3 is linker (1.2), h is 1-4, 1 -3, 1-3, 1 -2, 2-4, 2-3, 3-4, 1 , 2, 3, or 4.
[1129] In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (1.2), o, is 1-4, 1-3, 1-3, 1 -2, 2-4, 2-3, 3-4, 1 , 2, 3, or 4.
[1130] In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (1.2), o2 is 1 -4, 1-3, 1-3, 1 -2, 2-4, 2-3, 3-4, 1 , 2, 3, or 4.
[1131] In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (1.2), RaJ is H and R¾i is H. In some variations of formula (34) described in the paragraphs above in which at least one of LI , L2, and L3 i s linker (1.2), Rai is H and ¾{ is CH3. In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (1.2), Rai and RM are "^- . In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 i s linker (1.2), Rai and Rj>i are
Figure imgf000341_0001
. In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (1.2), two of CRaiRbi are '¾~N ¾
[1132] In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (1.2), Ra2 is H and &2 is H. In some variations of formula (34) described in the paragraphs above in which at least one of L I, L.2, and L3 is linker (1.2), Ra2 is H and Rb2 is CH3. In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (1.2), Ra2 and Rb2 are "^- . In some variations of formula (34) described in the paragraphs above in which at least one of LI , L2, and L3 is linker (1.2), Ra2 9
and ¾2 are L . In some variations ot formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (1.2), two of CRa2R|}2 are .
[1133] In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.2), is H and ¾i i s H. In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.2), Rci i s H and ¾i is CH3. In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.2), Rci and i are
Figure imgf000342_0001
. In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, L3,
O
and L4 is linker (1.2), Rci and ¾ί are . In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.2), two of CRciRd! are
[1134] In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.2), is H and ¾2 is H. In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.2), RC2 is H and R is CH3. In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.2), Rc2 and ^ are ^ . In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, L3,
9
and L4 is linker (1.2), Rc2 and ¾2 are . In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, L3, and L4 is linker (1.2), two of CRC2Rti2 are V
[1135] In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (1.2), ring A is
Figure imgf000342_0002
Figure imgf000343_0001
wherein R2 is C1-C6 linear or branched alkyl, aryl, or a five-membered nitrogen-containing heteroaromatic: or
Figure imgf000343_0002
Figure imgf000344_0001
optionally substituted with halo or C1 -C6 linear or branched afkyf
[1136] In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (1.2), n is 1-4, 1 -3, 1-3, 1 -2, 2-4, 2-3, 3-4, 1, 2, 3, or 4.
[1137] In some variations of formula (34) described in the paragraphs above, LI is linker (1.2). In some variations of formula (34) described in the paragraphs above, L2 is linker (1.2). In some variations of formula (34) described in the paragraphs above, L3 is linker (1.2). In some variations of formula (34) described in the paragraphs above, LI and L2 are linker (1.2). In some variations of formula (34) described in the paragraphs above, LI and L3 are linker (1.2). In some variations of formula (34) described in the paragraphs above, L2 and L3 are linker (1.2). In some variations of formula (34) described in the paragraphs above, LI, L2, and L3 are linker (1.2),
[1138] In some variations of formula (34) described in the paragraphs above, at least one of L I , L2, and L3 is linker (m.1):
Figure imgf000344_0002
in which n is 0-6, n is 1-4, and * is the attachment site for the cationic dye moiety D.
[1139] In some variations of formula (34) in which at least one of L I, L2, and L3 is linker (m. I), ft is 0-6, 0-5, 0-4, 0-3, 0-2, 0- 1 , 1-6, 1-5, 1 -4, 1-3, 1 -2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, 5-6, 0, 1, 2, 3, 4, 5, or 6.
[1140] In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (m. l ), ns is 1-4, 1-3, 1-2, 2-4, 2-3, 3-4, 1 , 2, 3, or 4, [1141] In some variations of formula (34) described in the paragraphs above, LI is linker (m. l). In some variations of formula (34) described in the paragraphs above, L2 is linker (m. l). In some variations of formula (34) described in the paragraphs above, L3 is linker (m. l). In some variations of formula (34) described in the paragraphs above, LI and L2 are linker (m. l). In some variations of formula (34) described in the paragraphs above, LI and L3 are linker (m. 1). In some variations of formula (34) described in the paragraphs above, L2 and L3 are linker (m. l). In some variations of formula (34) described in the paragraphs above, LI, L2, and L3 are linker (m. l).
[1142] In some variations of formula (34) described in the paragraphs above, at least one of LI , L2, and L3 is linker (n. l):
*
Figure imgf000345_0001
(n.1) , in which n2 is 1-5 and * is the attachment site for the cationic dye moiety D.
[1143] In some variations of formula (34) in which at least one of L I, L2, and L3 is linker (n. l), n2 is 1 -5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5.
[1144] In some variations of formula (34) described in the paragraphs above, LI is linker (n. l). In some variations of formula (34) described in the paragraphs above, L2 is linker (n. l). In some variations of formula (34) described in the paragraphs above, L3 is linker (n. l ). In some variations of formula (34) described in the paragraphs above, LI and L2 are linker (n. l). In some variations of formula (34) described in the paragraphs above, LI and L3 are linker (n. l). In some variations of formula (34) described in the paragraphs above, L2 and L3 are linker (n. l). In some variations of formula (34) described in the paragraphs above, LI, L2, and L3 are linker (n. l),
[1145] In some variations of formula (34) described in the paragraphs above, at least one of LI, L2, and L3 is linker (n.2):
Figure imgf000346_0001
(n.2)
, in which n2 is 1 -5 and * is the attachment site for the catiomc dye moiety D.
[1146] In some variations of formula (34) in which at least one of L I, L2, and L3 is linker (n.2), n2 is 1-5, 1 -4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1 , 2, 3, 4, or 5.
[1147] In some variati ons of formula (34) described in the paragraphs above, LI i s linker (n.2). In some variations of formula (34) described in the paragraphs above, L2 is linker (n.2). In some vari ations of formula (34) described in the paragraphs above, L3 is linker (n.2). In some variations of formula (34) described in the paragraphs above, LI and L2 are linker (n.2). In some variations of formula (34) described in the paragraphs above, LI and L3 are linker (n.2). In some variations of formula (34) described in the paragraphs above, L2 and L3 are linker (n.2). In some variations of formula (34) described in the paragraphs above, LI, L2, and L3 are linker (n.2).
[1148] In some variations of formula (34) described in the paragraphs above, at least one of L I, L2, and L3 is linker (o):
Figure imgf000346_0002
(o) , in which in which tii is 0-5, ¾ is 1-5, n3 is 0-5, and * is the attachment site for the cationic dye moiety D.
[1149] In some variations of formula (34) in which at least one of LI, L2, and 13 i s linker (o), nj is 0-5, 0-4, 0-3, 0-2, 0-1, 1-5, 1-4, 1-3, 1 -2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1, 2, 3, 4, or 5. [1150] In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (o), n2 is 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5.
[1151] In some variations of formula (34) described in the paragraphs above in which at least one of LI, L2, and L3 is linker (o), n3 is 0-5, 0-4, 0-3, 0-2, 0-1, 1 -5, 1-4, 1 -3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, I, 2, 3, 4, or 5.
[1152] In some variati ons of formul a (34) described in the paragraphs above, LI i s linker (o). In some variations of formula (34) described in the paragraphs above, L2 is linker (o). In some variations of formula (34) described in the paragraphs above, L3 is linker (o). In some variations of formula (34) described in the paragraphs above, LI and L2 are linker (o). In some variations of formula (34) described in the paragraphs above, LI and L3 are linker (o). In some variations of formula (34) described in the paragraphs above, L2 and L3 are linker (o). In some variations of formula (34) described in the paragraphs above, LI, L2, and L3 are linker (o).
[1153] In some variations of formula (34) described in the paragraphs above, at least one of LI, L2, and L3 is linker (p):
Figure imgf000347_0001
W> , in which m is 0-5, n2 is 1 -5, n3 is 0-5, and * is the attachment site for the cationic dye moiety D.
[1154] In some variations of formula (34) described above in which at least one of LI, L2, L3, and L4 is linker (p), ns is 0-5, 0-4, 0-3, 0-2, 0-1, 1-5, 1 -4, 1-3, 1 -2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1, 2, 3, 4, or 5.
[1155] In some variations of formula (34) described above in which at least one of LI, L2, L3, and L4 is linker (p), n2 is 1-5, 1-4, 1-3, 1 -2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, I, 2, 3, 4, or 5. [1156] In some variations of formula (34) described above in which at least one of LI, L2, L3, and L4 is linker (p), n3 is 0-5, 0-4, 0-3, 0-2, 0-1, 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1, 2, 3, 4, or 5.
[1157] In some variations of formula (34) described in the paragraphs above, LI is linker (p). In some variations of formula (34) described in the paragraphs above, L2 is linker (p). In some variations of formula (34) described in the paragraphs above, L3 is linker (p). In some variations of formula (34) described in the paragraphs above, LI and L2 are linker (p). In some variations of formula (34) described in the paragraphs above, LI and L3 are linker (p). In some variations of formula (34) described in the paragraphs above, L2 and L3 are linker (p). In some variations of formula (34) described in the paragraphs above, LI, L2, and L3 are linker (p).
[1158] In some variations of formula (34) described in the paragraphs above, at least one of LI, L2, and L3 is linker (q):
Figure imgf000348_0001
(q) , in which n4 is 0-5, n2 is 1-5, and * is the attachment site for the cationic dye moiety D.
[1159] In some variations of formula (34) in which at least one of LI, L2, and L3 is linker (o), n4 is 0-5, 0-4, 0-3, 0-2, 0-1, 1-5, 1-4, 1-3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1, 2, 3, 4, or 5.
[1160] In some variations of formula (34) described above in which at least one of LI, L2, L3, and L4 is linker (q), n2 is 1-5, 1 -4, 1-3, 1 -2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1, 2, 3, 4, or 5.
[1161] In some variations of formula (34) described in the paragraphs above, LI is linker (q). In some variations of formula (34) described in the paragraphs above, L2 is linker (q). In some variations of formula (34) described in the paragraphs above, L3 is linker (q). In some variations of formula (34) described in the paragraphs above, LI and L2 are linker (q). In some variations of formula (34) described in the paragraphs above, LI and L3 are linker (q). In some variati ons of formula (34) described in the paragraphs above, L2 and L3 are linker (q). In some variations of formula (34) described in the paragraphs above, LI, L2, and L3 are linker (q). [1162] In some variations of formula (34) described in the paragraphs above, at least one of LI, L2, and L3 is linker (r):
Figure imgf000349_0001
, in which nj is 0-5, «? is 1-5, n3 is 0-5, and * is the attachment site for the cationic dye moiety D.
[1163] In some of variations of formula (34) in which at least one of LI , L2, and L3 is linker (r), n} is 0-5, 0-4, 0-3, 0-2, 0- 1, 1-5, 1-4, 1-3, 1 -2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, I, 2, 3, 4, or 5.
[1164] In some of variations of formula (34) described in the paragraphs above in which at least one of LI , L2, and L3 i s linker (r), n2 is 1-5, 1-4, 1 -3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 1 , 2, 3, 4, or 5.
[1165] In some of variations of formula (34) in which at least one of LI, L2, and L3 is linker (r), n3 is 0-5, 0-4, 0-3, 0-2, 0-1 , 1-5, 1 -4, 1 -3, 1-2, 2-5, 2-4, 2-3, 3-5, 3-4, 4-5, 0, 1 , 2, 3, 4, or 5.
[1166] In some variations of formula (34) described in the paragraphs above, LI is linker (r). In some variations of formula (34) described in the paragraphs above, L2 is linker (r). In some variations of formula (34) described in the paragraphs above, L3 is linker (r). In some variations of formula (34) described in the paragraphs above, LI and L2 are linker (r). In some variations of formula (34) described in the paragraphs above, LI and L3 are linker (r). In some variations of formula (34) described in the paragraphs above, L2 and L3 are linker (r). In some variations of formula (34) described in the paragraphs above, LI, L2, and L3 are linker (r).
[1167] In some variations of formula (34) described in the paragraphs above, at least one of LI, L2, and L3 is linker (s):
Figure imgf000350_0001
, in which n2 is 0-5, n2 is 1 -5, n3 is 0-5, and * is the attachment site for the cationic dye moiety D.
[1168] In some variations of formula (34) described in the paragraphs above, LI is linker (s). In some variations of formula (34) described in the paragraphs above, L2 is linker (s). In some variations of formula (34) described in the paragraphs above, L3 is linker (s). In some variations of formula (34) described in the paragraphs above, LI and L2 are linker (s). In some variations of formula (34) described in the paragraphs above, LI and L3 are linker (s). In some variations of formula (34) described in the paragraphs above, L2 and L3 are linker (s). In some variations of formula (34) described in the paragraphs above, LI, L2, and L3 are linker (s).
[1169] In some variations of formula (34) described in the paragraphs above, LI is absent. In some variations of formula (34) described in the paragraphs above, L2 is absent. In some variations of formula (34) described in the paragraphs above, L3 is absent. In some variations of formula (34) described in the paragraphs above, LI and L2 are absent. In some variations of formula (34) described in the paragraphs above, LI and L3 are absent. In some variations of formula (34) described in the paragraphs above, L2 and L3 are absent. In some variations of formula (34) described in the paragraphs above, LI, L2, and L3 are absent,
[1170] In some variations of formula (34), each of LI, L2, and L3 is a different linker. In some variations of formula (34), each of LI, L2, and L3 is the same linker. In some variations of formula (34), LI is a first linker and each of L2 and L3 is the same second linker, wherein the first and second linkers are different. In some variations of formula (34), L2 is a first linker, and each of LI and L3 is the same second linker, wherein the first and second linkers are different.. In some variations of formula (34), L3 is a first linker and each of LI and L2 is the same second linker, wherein the first and second linkers are different.
[1171] In some variations of formula (34) described in the paragraphs above, Dl is safranin-O. In some variations of formula (34) described in the paragraphs above, D2 is safranin-O. In some variations of formula (34) described in the paragraphs above, D3 is safranin-O. In some variations of formula (34) described in the paragraphs above, Dl and D2 are safranin-O. In some variations of formula (34) described in the paragraphs above, 1)1 and D3 are safranin-O. In some variations of formula (34) described in the paragraphs above, D2 and D4 are safranin-O.
[1172] In some variations of formula (34) described in the paragraph above, the pendant phenyl ring of Dl is unsubstituted. In some variations of formula (34) described in the paragraph above, the pendant phenyl ring of Dl is substituted with 1-3 (e.g., 1 -3, 1-2, 1 , 2, or 3) electron-donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— -NH2,— NHR,— NR2,— OH,— O",
— NHCOCH3,— NHCOR,— OCH3,—OR,— C2H5,— R, and— C6¾, wherein R is C 1-C6 linear or branched alky! (e.g., C 1-C6, C 1-C5, C1-C4, C 1-C3, C1-C2, CI , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of Dl is substituted, the substituents are selected independently from— -NO2,— - R3 +, halo (e.g., F, Br, CI, I), trihalide (e.g.,— CF3,— CCI3,— CBr3, (' ! : )..— CN,— S03H,— COOH,— COOR,— CHO, and — COR, wherein R is C1-C6 linear or branched alkyl (e.g., C 1 -C6, C 1-C5, C1 -C4, C 1-C3, C l- C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
[1173] In some variations of formula (34) described in the two paragraphs above, the pendant phenyl ring of D2 is unsubstituted. In some variations of formula (34) described in the paragraph above, the pendant phenyl ring of D2 is substituted with 1-3 (e.g., 1-3, 1-2, I, 2, or 3) electron- donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— NH2,— NHR,— NR2,— OH,— O",
— NHCOCH3,— -NHCOR, --OCH3,—OR, --C2H5, --R, and C,,l k wherein R is C1-C6 linear or branched alkyl (e.g., C I-C6, C 1-C5, C 1-C4, C I-C3, C1-C2, C I , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched aikyi). In some embodiments in which the pendant phenyl ring of D2 is substituted, the substituents are selected independently from— -N02,— -NR3 +, halo (e.g., F, Br, CI, I), trihalide (e.g.,— CF3,— CCI3,— CBr3,— CI3),— CN,— SO3H, -—COOH,— COOR,—CHO, and — COR, wherein R is C1.-C6 linear or branched al kyl (e.g., C I -C6, C1-C5, C I -C4, C 1 -C3, C l- C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl). [1174] In some variations of formula (34) described in the three paragraphs above, the pendant phenyl ring of D3 is unsubstituted. In some variations of formula (34) described in the paragraph above, the pendant phenyl ring of D3 is substituted with 1 -3 (e.g., 1 -3, 1-2, 1 , 2, or 3) electron- donating or electron-withdrawing groups, which may be at any available position on the pendant phenyl ring. In some embodiments in which the pendant phenyl ring of D3 is substituted, the substituents are selected independently from— -NH2,— NHR,— NR2,— OH,— O",
— NHCOCH3,— NHCOR,— OCH3,—OR,— C2H5,— R, and C-j k wherein R is C 1-C6 linear or branched alky! (e.g., C 1-C6, C 1-C5, C1-C4, C 1-C3, C1-C2, CI , C2-C6, C2-C5, C2- C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5-C6, C5, or C6 linear or branched alkyl). In some embodiments in which the pendant phenyl ring of 1)3 is substituted, the substituents are selected independently from— 02,— R3 , halo (e.g., F, Br, CI, I), trihaiide (e.g., --CF3, --CCI3, ---CBr3, --CI3), --CN, SO : I L --COOH, --COOR, CFIO, and — COR, wherein R is C1-C6 linear or branched alkyl (e.g., C 1 -C6, C 1-C5, C1 -C4, C 1-C3, C l- C2, C I, C2-C6, C2-C5, C2-C4, C2-C3, C2, C3-C6, C3-C5, C3-C4, C3, C4-C6, C4-C5, C4, C5- C6, C5, or C6 linear or branched alkyl).
Examples of cationic dye dimers and trimers comprising safranin-0 are provided below in Table 1. One of ski ll in the art can readily visualize and prepare other cationic dye multimers in which other cationic dye moieties are used in place of one or more of the safranin-0 moieties.
Table 1.
Figure imgf000352_0001
Figure imgf000353_0001
Figure imgf000354_0001
Figure imgf000355_0001
Figure imgf000356_0001
Figure imgf000357_0001
Figure imgf000358_0001
[1175] Each reference cited in this disclosure is incorporated herein in its entirety. The following examples illustrate but do not limit the scope of the disclosure set forth above.
EXAMPLE L Schematic synthesis plan for preparing a cationic dye dimer
Figure imgf000359_0001
CAMPLE 2. Methods for preparing saframn~G derivatives
177] This example provides schematic synthesis plans for safrani n-0 derivatives.
Figure imgf000360_0001
Na2Cr207 00 deg C
Figure imgf000360_0002
EXAMPLE 3. Examples of linking cationic dye moieties using diamino linkers
[1178] Cationic dye moieties can be linked using acetamido groups through diamino linkers, as illustrated below:
Safranin dimers
+ Diamine
+ amide
coupling agent
Figure imgf000361_0001
[1179] Linkers which can be used include linkers incorporating alkyl chains, such as lene glycol moieties, such as s containing amines which can be positively charged,
s
Figure imgf000361_0002
uch as and linkers incorporating alkyl chains which contai positively c amino acids such as Lys (illustrated below), His, or Ar :
Figure imgf000361_0003
(in this instance, the ε-amino group would initially be in a protected state). EXAMPLE 4. Preparation of Linear Cationic Dye Multimers
[1180] Cationic dye moieties can be linked linearly using the scheme below, which illustrates preparation of a linear trimer comprising safranin-0 moieties. The same process can be repeated as desired to prepare a cationic dye multimer comprising e.g., 4, 5, or 6, cationic dye moieties.
Figure imgf000362_0001
EXAMPLE 5. Preparation of Branched Cationic Dye Multimers
[1181] Cationic dye moieties can be linked to form branched multimers using the scheme below, which illustrates preparation of a branched trimer comprising safranin-0 moieties. The same process can be repeated as desired to prepare a cationic dye multimer comprising, e.g., 4, or 5 cationic dye moieties.
Figure imgf000363_0001
cid
1. EDCi, DMF
BocHN, 2. HC!
Figure imgf000363_0002
[1182] Tetramers can be prepared using a similar scheme and, for example, biphenyl-3,3',5,5'-
tetracarboxylic acid,
Figure imgf000363_0003
; instead of as used in the scheme above. Higher multimers can be prepared similarly, using the appropriate
polvcarboxvlate linker. .exane-l ,6-diylbis(azanediyl))bis(3-amino-2,8-dimethyl-5-phenylphenazin-
Figure imgf000364_0001
Step-1 : Synthesis of 3-amino-7-(tert-butoxycarbonylamino)-2,8-dimethyl-5-phenylphenazin-5- ium chloride
[1183] To a solution of Safranin-'O' (5.2 g, 14,8 rrmiol) in DMF (50 mL), cooled to -40 °C, was added sodium hydride (1.18 g, 29.5 mmoi) and the reaction mass was stirred at the same temperature for I h. Boc anhydride (2,91 g, 13,97 rmrsol) was added at the same temperature and the reaction mass was stirred at the same temperature for another Ih. The progress of the reaction was monitored by LCMS and TLC (System: 10% MeOH in DCM). The reaction was quenched by adding water (20 mL) and the solid obtained was filtered and purified by column
chromatography (silica gel 100-200 mesh, eluent system-10 % MeOH:DCM) to obtain 3-amino- 7-(tert-butoxycarbonylamino)-2,8-dimethyl-5-phenylphenazin-5-ium chloride (1 g). Step-2: Synthesis of tert-butyl N-(8-amino-3,7-dirnethyl-l O-phenyl-phenazin-10-ium-2-yl)-N-[6-
[(8-amino-3,7-dimethyl-10-phenyl-phenazin-10-ium-2-yl)-tert-butoxycarbonyl- arnin o]hexy 1 ] carb amate di chl ori de
[1184] To a solution of 3-amino-7-(tert-butoxycarbonylamino)-2,8-dimethyl-5-phenylphenazin-
5-ium chloride (225 mg,0.5 mmol) in DMF (2.5 mL), cooled to -30 0 C, was added sodium hydride (40 mg, 1.0 mmol) and the reaction mass was stirred at the same temperature for Ih. 1,6- Diiodohexane (85 mg, 0.25 mmol) was added and the reaction was stirred at the same temperature for 2 min and at 0 0 for 20 min. Additional 1,6-diiodohexane (33 mg, 0.097 mmol) was added and the reaction mixture was stirred at RT for 5 min. The reaction mixture was monitored by LCMS. After detection of product, the reaction was quenched with water (5 mL). The solid product obtained was filtered, dissolved in 20% MeOH/DCM solution (20 mL) and concentrated under reduced pressure to get 100 mg crude product, which was purified by reverse phase HPLC to get pure tert-butyl N-(8-amino-3,7-dimethyl-10-phenyl-phenazin-10-ium-2-yl)- N-[6-[(8-amino-3,7-dimethyl-l O-phenyl-phenazin-10-ium-2-yl)-tert-butoxycarbonyl- amino]hexyl]carbamate di chloride (6 mg.)
Step-3 : Synthesis of 7,7,~(hexane~l,6-diylbis(azanediyl))bis(3-amino-2,8-dimethyl-5-phenyl phenazin-5-ium) chloride.
[1185] 7,7'-(2,2, 15, 15-Tetramethyl-4, 13-dioxo-3, 14-dioxa-5, 12-diazahexadecane-5, 12- diyl)bis(3-amino-2,8-dimethyl-5-phenylphenazin-5-ium) chloride (5 mg, 0.13 mmol) was dissolved in DCM (1 mL). Trifluoroacetic acid (1 mL) was added and the reaction was stirred at RT for 2h. The desired product was detected by LCMS and NMR. The reaction mixture was concentrated under vacuum to obtain the desired product, which was triturated with diethyl ether and pentane. 1HNMR (CD3OD): δ (ppm): 7.90-7.70 (m, 10! 1). 7.55-7.50 (m, 4H), 6.05 (s, 2H), 5.73 (s, 2H), 3.05 (m, 4H), 2,4 (s, 6H), 2.35 (s, 6H), 1.55-1.42 (m, 61 1 ), 1.22-1.15 (m, 6H).
LCMS: 740(M+) and 370 (half fragment).
EXAMPLE 7, Synthesis of Compounds 2 and 3,
[1186] This example provides a synthesis route for compounds 2 and 3 , Appropriate starting materials can be obtained using the methods as presented in Example 2.
Figure imgf000366_0001
ompoun : = EXAMPLE 8. Synthesis of Compound 4
Synthesis of 7,7'-(octane-l,8-diylbis(azanediyl))bis(3-amino-2,8-dimethyl-5-phenylphenazi ium) chloride
Figure imgf000367_0001
[1187] To a stirred solution of Safranin-0 (1 .05 g, 3.0 mmol) in 15 nil. ofN,N~
dimethylacetamide was added potassium carbonate (0.55 g, 4.0 mmol) and stirred at RT for 15 min. 1,8-Dibromooctane (272 mg, 1.0 mmol) was then added dropwise into the reaction mixture followed by the addition of potassium iodide (332 mg, 2.0 mmol). The reaction mixture was then stirred at 60 °C for 24h under nitrogen. The reaction mixture was then allowed to cool to RT, 20 mL water was added and the cmde reaction mixture was Ivophilized. The mixture was then purified by column chromatography (silica gel, 100-200 mesh, 0-10% MeOH in DCM). The product obtained by column chromatography was re-purified by HPLC to afford the desired product as a brown solid. 1H NMR (DMSO-d6): δ (ppm): 7.90-7.75 (m, 12H), 7.65-7.55 (m, 7H), 6.0 (s, 2H), 5.55 (s, 2H), 2.98 (m, 4H), 2.30 (s, 12 H), 1.35 (m, 4H), 1.05 (bs, 8H). 1HNMR (CD3OD) δ (ppm): 7.90-7.70 (m, 10H), 7.55-7.50 (m, 4H), 6,05 (s, 2H), 5,73 (s, 2H), 3 ,05 (m, 4H), 2.4 (s, 6H), 2.35 (s, 6H), 1.55-1.42 (m, 6H), 1.22-1.15 (m, 6H). LCMS: 740 ( \ f · ) and 370 (half fragment). EXAMPLE 9. Sysithesis of Compound 6
Synthesis of 3-amino-7-[(6-{ [3,5-bis({6-[(7-amino-2,8-dimethyl-5-phenyl-5X5, 10-phenazin-5- ylium-3-yl)amino]hexyl}carbamoyl)p^
5, 10-phenazin-5-ylium
Figure imgf000368_0001
Figure imgf000369_0001
Step-1 : Synthesis of 2-(6-iodohexyl)isoindoline-l ,3-dione
[1188] To a suspension of potassium phthal amide (700 mg, 3,7 mmol) in DMF (30 mL) was added 1 ,6-diiodohexane (3,83 g, 1 1 ,33 mmol) and the reaction mass was heated atw 80 °C for 1 h. (The reaction mass became clear on heating). The reaction mixture was cooled to RT, diluted with diethyl ether (100 mL) and water (100 mL), the organic layers were separated, and the aqueous layer was again extracted with diethyl ether (2x100 mL). The combined organic layer was washed with water (200 mL) and saturated brine solution (200 mL) The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain the product, which was purified by column chromatography (silica gel: 100-200 mesh; Eluent: 10 % ethyl acetate in hexane) to obtain pure product as white solid (2.1 g),
Step-2: Synthesis of tert-butyl 'N-[8-(tert-butoxycarbonylamino)-3,7-dimethyl-10-phenyl- phenazin-10-ium-2-yl]-N-[6-(l,3-dioxoisoindolin-2-yl)hexyl]carbamate
[1189] To a solution of 3,7-bis(tert-butoxycarbonylamino)-2,8-dimethyl-5-phenylphenazin-5- ium (500 mg, 0.90 mmol) in DMF (5 mL) was added cesium carbonate (1.48 g, 4.54 mmol) and the mixture stirred at RT for 10 min. 2-(6-Iodohexyl)isoindoline-l,3-dione (422 mg, 1.18 mmol) was added and the reaction mass was stirred at RT overnight. The reaction was monitored by LCMS and TLC. The reaction mass was diluted with EtOAc (25 mL) and water (25 mL), and the layers were separated. The aqueous layer was again extracted with EtOAc (2x25 mL). The combined organic layer was washed with water (2x100 mL), and saturated brine solution (200 mL), then dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain the product. This was purified by column chromatography by using neutral alumina and an eluent system of 0 to 2% Methanol in DCM) to obtain pure product (200 mg.)
Step-3 : Synthesis of tert-butyl N-(6-aminohexyl)-N-[8-(tert-butoxycarbonylamino)-3,7- dimethyl-10-phenyl-phenazin-10-ium-2-yl]carbamate
[1190] To a solution of 3-(tert-butoxycarbonyl(6-(l,3-dioxoisoindolin-2-yl)hexyl)amino)-7-(tert- butoxycarbonylamino)-2,8-dimethyl-5-phenylphenazin-5-ium (800 mg, 1.04 mmol) in ethanol (40 mL) was added hydrazine hydrate monohydrate (1.072 mg, 20.8 mmol) and the reaction mixture was heated to reflux for 90 min. The reaction was monitored by TLC and LCMS. The solvent was evaporated under reduced pressure to dryness. The residue was dissolved in diethyl ether ( 150 mL) and filtered, the filtrate was concentrated under reduced pressure to obtain the crude product which was purified by column chromatography using neutral alumina (Eluent System :0 to 3% MeOH in DCM) to obtain pure product (410 mg). Step-4: Synthesis of tert-butyl N-[6-[[3,5-bis[6-[tert-butoxycarbonyl-[8-(tert- butoxycarbonylamino)-3 , 7-dimethyl- 10-phenyl-phenazin- 10-ium-2- yl]amino]hexylcarbamoyl]benzoyl]amino]hexyl]-N-[8-(tert-butoxycarbonylamino)-3,7- dimethyl- 10-phenyl -phenazin- 10-ium-2-y f jcarbamate trichloride
[1191] To a solution of 3-((6-aminohexyl)(tert-butoxycarbonyl)amino)-7-(tert-butoxycarbonyl amino)-2,8-dimethyl-5-phenylphenazin-5-ium (243 rng, 0.395 mmol) in DMF(3 mL) was added DIPEA (233 mg, 1.80 mmol) and stirred at RT for 10 min. Benzene-l,3,5-tricarbonyl trichloride (30 mg, 0.1 13 mmol) was added and the reaction was stirred at RT overnight. The reaction was monitored by TLC and LCMS. The reaction mass was diluted with EtOAc (30 mL) and water (30 mL), and the organic layer was separated. The aqueous layer was again extracted with EtOAc (2x30 mL), the combined organic layer was washed with water (100 mL) and saturated brine solution (100 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain the product which was purified by column chromatography using neutral alumina (Eluent: 0.2-1% MeOH in DCM) to obtain pure product (65 mg.)
Step-5: Synthesis of N1 ,N3 ,N5-tris[6-[(8-amino-3, 7-dimethyl- 10-phenyl -phenazin- 10-ium-2- yl)amino]hexyl]benzene-l,3,5-tricarboxamide trichloride
[1192] To a solution of the diboc protected trimer (65 mg, 0.0325 mmol) in DCM (5 mL) was added trifluoroacetic acid (01 mL) and the reaction mixture was stirred at RT overnight. The reaction mixture was monitored by LCMS. The reaction mass was concentrated under reduced pressure to dryness and purified by reverse phase HPLC to obtain the product to obtain the product as the acetate counter anion. The product was dissolved in ethanol-HCl (20 mL) and concentrated to diyness (3 times), and the solid obtained was washed with water (20 mL) to remove inorganic impurities. The solid obtained was lyophilized to get the product (6.6 mg) which was confirmed by LCMS and MR. !H NMR (CD3OD): δ (ppm): 8.25 (s, 3 H), 7.4-7.90 (m, 15 H), 6.6 (s, 6 H), 6.15 (s, 6 H), 3.1-3.5 (m, 12 H),2,2-2.3 (m, 18 H), 1.3-1.9 (m, 24 H). M+ ( 1397), M/2 (699.1), M/3 (467, 1),
EXAM PLE 10. Synthesis of Compounds 18 and 19
Synthesis of 3-amino-7-{[(2-{[(7-amino-2,8-dimethyl-5-phenyl-5 i>,10-phenazin-5-ylium-3- yl)amino]methyl}phenyl)methyl]amino}-2,8-dimethyl-5-phenyl-5 °, 10-phenazin-5-ylium and 3- amino-7-{[(2-{[(7-amino-2,8-dimethyl-5-phenyl-5 °,10-phenazin-5-ylium-3- yl)amino]methyl}phenyl)methyl]amino}-2,6-dimethyl-5-phenyl-5 °, 10-phenazin-5-ylium
Figure imgf000372_0001
xycarbonyl(2-((tert-butoxycarbonyl(7-(tert-butoxycarbonylamino)-2,8-dimethyl-5- phenylphenazin-5-ium-3-yl)amino)niethyl)benzyl)aniino)-3-(tert-butoxycarbonylamino)-2,6- dimethy 1-5 -phenylphenazin- 5 -ium
[1193] To a stirred solution of 3 ,7-bis(tert-butoxycarbonylamino)-2,8-dimethyl-5- phenylphenazin-5-ium chloride & 3,7-bis(tert-butoxycarbonylamino)-2,6-dimethyl-5- phenylphenazin-5-ium chloride (500 mg, 0.90mmol) in 5 mL of DMF was added cesium carbonate (880 mg, 2.70 mmol) and the mixture stirred at RT for 15 min. The reaction mixture was then cooled to 0°C and o-xylene dibromide (132 nig, 0.50 mmol, diluted with 1ml of DMF) was added drop wise. The reaction mixture was stirred at RT for 12 h. The reaction was monitored by TLC and LCMS. After completion of reaction, mixture was diluted with ice-cold water and filtered. The solid residue obtained was dissolved in diethyl ether (50 mL) and washed with brine solution (3x20 mL). The organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure to afford cmde product which was then purified by column chromatography (neutral alumina, eluent 0-20% EtOAc in hexane) to afford the desired product as a dark brown solid (250 mg).
Step-2: Synthesis of 7,7'-(l,2-phenylenebis(methylene))bis(azanediyl)bis(3-amino-2,8-dimethyl- 5-phenylphenazin-5-ium) chloride & 3-amino-7-(2-((7-amino-2,8-dimethyl-5-phenylphenazin-5- ium-3-ylamino)methyl)benzylamino)-2,6-dimethyl-5-phenylphenazin-5-ium chloride:
11194] To a stirred solution of 7,7'-(l,2-phenylenebis(methylene))bis(tert- butoxycarbonyiazanediyl)~bis^
ium) chloride (250 mg, 0.27 mmol) in 5 mL of DCM was added TFA (1 mL) at 0°C dropwise and the mixture stirred at RT for 12h. The reaction was monitored by TLC and LCMS. After completion of reaction, the solvent was removed under reduced pressure to dryness and the residue purified by reverse phase HPLC to afford two peaks of the same mass. Both peaks were then treated separately with methanol ic HC1 and dried, then washed with water and dried again to afford desired product. (Compound 18): 8mg. (Compound 19): 8mg. 'H MR Compound 18: (DMSO-d6): δ (ppm): 8, 15 (t, 2H), 7.90 (d, 4H), 7.85-7.75 (m, 6H), 7.6 (m, 3H), 7.40 (d, 4H), 7.05 (m, 2H), 6.65 (m, 2H), 5.95 (s, 2H), 5.45 (s, 2H), 4.10 (m, 4H), 2.40 (s, 6H), 2.30 (s, 6 H). LCMS: 732 (M+), 366(M/2), Compound 19: (DMSO-d6): δ (ppm): 8.15 (bs, 1 1 1 ).. 7.95 (s, 1H), 7.90-7.75 (m, 51 1 ), 7.74-7.60 (m, 7H), 7.42 (d, 2H), 7.20-7.10 (m, 2H), 7.05 (t, 1H), 6.65 (d, 1 1 1). 6.10 (s, 1 1 1 ).. 5.95 (s, 1H), 5,62 (s, 1H), 4,58 (m, 2H),4.4Q (m, 21 1 ).. 2.40 (s, 3H), 2.30 (s, 6 1 1 ), 1.48 (s, 3H). LCMS: 732 { \ I ). 366 (M/2).
EXAMPLE 11. Synthesis of Compound 20
Synthesis of (3-amino-7-{[6-({4-[4-({6-[(7-amino-5-chloranuide-2,8-dimethyl-5-phenyl-5 D, 10- phenazin-5-ylium-3-yl)amino]hexyl }carbamoyl)phenyl]phenyl}formamido)hexyl]amino}-2,8- dimethyl-5-phenyl-5 6, 10-phenazin-5-ylium-5-e)chloranuide
Figure imgf000374_0001
Step-1 : Synthesis of bis(2,5-dioxopyrrolidin-l-yl) biphenyl-4,4'-dicarboxylate
[1195] To a stirred solution of biphenyl-4,4'-dicarboxylic acid (500 nig, 2.06 mmoi) in 10 niL of DMF was added N-hydroxysuccinimide (594 rag, 5.16 mmol) and dicyclohexylcarbodiimide
(1.06 g, 5.16 mmol) at 0°C and the mixture stirred at RT overnight. The reaction mixture was filtered and the filtered cake was washed with EtOAc. The washings and filtrate were combined, washed with brine solution (3x20 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford a crude product that was dissolved in DCM and again filtered. The DCM layer was concentrated under reduced pressure to afford desired product (600 mg).
Step-2: Synthesis of tert-butyl N-[8-(tert-butoxycarbonylamino)-3,7-dimethyl-10-phenyl- phenazin-10-ium-2-yl]-N-[6-[[4-[4-[6-[tert-butoxycarbonyl-[8-(tert-butoxycarbonylamino)-3,7' dimethyl- 10-phenyl -phenazin-10-ium-2- yl]amino]hexylcarbamoyl]phenyl]benzoyl]amino]hexyl]carbamate dichloride
11196] Bis(2,5-dioxopyrrolidin-l -yl)biphenyl-4,4'-dicarboxylate (20 mg, 0.045 mmol) and 3-((6- aminohexyl)(tert-butoxycarbonyl)amino)-7-(tert-butoxycarbonylamino)-2,8-dirnethyl-5- phenylphenazin-5-ium chloride (65.5 mg, 0.100 mmol) were dissolved in 2 ml of DMF and tri ethyl amine (14 mg) was added. The reaction mixture was stirred at RT for 16 h. After completion of reaction, the mixture was diluted with ice-cold water and extracted with EtOAc. The organic layer was washed with brine solution (4x10 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford the crude product, which was purified by column chromatography (neutral alumina) to afford the desired product (70 mg).
Step-3 : Synthesis of N-[6-[(8-amino-3,7-dimethyl-10-phenyl-phenazin-10-ium-2- yl)amino]hexyl]-4-[4-[6-[(8-amino-3,7-dimethyl-10-phenyl-phenazin-10-ium-2- yl)amino]hexyicarbamoyl]phenyi] benzamide dichloride
11197] The product from Step-2 (70 mg) was dissolved in 2 mL of DCM and TFA (0.5 mL) was added at 0°C dropwise and stirred at RT for 12 h. The reaction was monitored by TLC and LCMS. After completion of reaction, solvent was removed under reduced pressure to dryness to obtained crude product which was purified by reverse phase HPLC. The product obtained after purification was then treated with Methanolic HCl and dried and then washed with water and freeze dried to afford the desired product (6 mg). 1H NMR ISO- ·!(?): δ (ppm): 8.56 (t, 2H), 7.97-7.95 (d, 4H), 7.90-7.75 (m, 12H), 7,70-7,65 (m, 2H), 7.62 (d, 4H), 7,60-7,45 (m, 3H), 6.02 (s, 2H), 5.58 (s, 2H), 3.25 (m, 4H), 2.98 (m, 41 ! ). 2.35 (s, 6 H), 2.33 (s, 6H), 1.50-1.42 (m, 41 ! ). 1.40-1.30 (m, 4H), 1.20-1.05 (m, 81 1 ).
EXAMPLE 12. Synthesis of Compound 21
Synthesis of (3-amino-7-{ 10~[(7-amino-5-chloranuide-2,8~dimethyl~5-phenyl-5 6, 10-phenazin-
5-ylium-3-yl)carbamoyl]decanamido}-2,8-dimethyl-5-^^
e)chloranuide
Figure imgf000376_0001
Safranin-0
Step-2 NaH
DMF
RT-16 hrs
Figure imgf000376_0002
Step-1 : Synthesis of bis(2,5-dioxopyrrolidin-l -yl) undecanedioate
11198] To a stirred solution of undecanedioic acid (500 mg, 2.31 mmol) in 10 mL of anhydrous THF was added N-hydroxysuccinimide (585 mg, 5.09 mmol) and dicyclohexylcarbodiimide
(1.08 g, 5.09 mmol) at 0°C and then allowed to stir at RT for 16 h. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The product obtained was washed with diethyl ether and dried to afford the desired product (725 mg).
Step-2: Synthesis of (3-amino~7-{ 10-[(7-amino-5-c-hloranuide-2,8-dimethyl-5-phenyl-5 6, 10- ph6nazin-5~ylium-3~yl)earbamoyi]deeanamido}-2,8-dim
ylium-5-e)chloranuide
[1199] To a stirred solution of Safranin-0 (350 mg, 1.0 mmol) in 10 mL of DMF was added sodium hydride (60 mg, 1.5 mmol) at 0°C and stirred for 10 min, bis(2,5-dioxopyrrolidin-l-yl) undecanedioate (205 mg, 0.5 mmol) was added and allow to stir at RT for 16 h. After completion of reaction, the mixture was diluted with ice-cold water and filtered. The product obtained was dried and purified by reverse phase HPLC. The purified product was treated with Methanolic HCl (5 times), dried and washed with water and freeze dried to afford the desired product (5 mg). 1H NMR (CD3OD): δ (ppm): 8,56 (s, IH), 8, 18 (s, 2H), 7,97-7,95 (m, 3H), 7.90-7.80 (m, 6H), 7.60-7.50 (m, 4H), 6, 18 (s, 2H), 2.55 (s, 6H), 2.45-2.40 (m, 10H), 1.65-1.58 (m, 4H), 1.35- 1.25 (m, 10H). EXAMPLE 13. Synthesis of Compounds 22 and 23
Synthesis of [3-amino-7-({9-[(7-amino-5-chloranuide-2,8-dimetty ylium-3-yl)amino]nonyl}amino)-2,8-dimethyl-5-ph^^
ejjchioranuide and [3-amino-7-({9-[(7-amino-5-chloranuide-4,8-dimeth^^ phenazin-5-ylium-3-yl)amino]nonyl}amin^
e]chloranuide
Figure imgf000377_0001
Figure imgf000378_0001
Figure imgf000378_0002
Step-1 : Synthesis of 7,7'-(2,2, 18, 18-tetramethyl-4, 16-dioxo-3, 17-dioxa-5, 15-diazanonadecane- 5, 15-diyl)bis(3-(tert-butoxycarbonylamino)-2,8-dimethyl-5-phenylphenazin-5-ium) chloride and 7-(tert-butoxycarbonyl(9-(tert-butoxycarbonyl(7-(tert-butoxycarbonylamino)-2,8-dimethyl-5- phenylphenazin-5-ium-3-yl)amino)nonyl)amino)-3-(tert-butoxycarbonylamino)-2,6-dimethyl-5- phenylphenazin-5-ium chl ori de:
[1200] To a stirred solution of mixture of 3,7-bis(tert-butoxycarbonylamino)-2,8-dimethyl-5- phenylphenazin-5-ium chloride and 3,7-bis(tert-butoxycarbonylamino)-2,6-dimethyl-5- phenylphenazin-5-ium chloride (500 rng, 0.909 mmol) in 10 rnL of DMF was added cesium carbonate (738 mg, 2.27 mmol) and stirred at RT for 5 min. The reaction mixture was cooled to 0°C and 1 ,9-dibromononane (156 mg, 0.545 mmol, diluted with J mL of DMF) was added dropwise. The reaction mixture was stirred at RT for 12 h. The reaction was monitored by TLC and LCMS. After completion of reaction, the mixture was diluted with ice-cold water and filtered. The solid residue obtained after filtration was dissolved in diethyl ether (200 mL) and washed with brine solution (3x50 mL). The ether layer was dried over anhydrous sodium sulfate, concentrated under reduced pressure to afford the crude product which was purified by column chromatography (neutral alumina, eluent 0-20% EtOAc in hexane) to afford the desired product (mixture of 2 products of same mass) as a dark brown solid (400 mg),
Step-2: Synthesis of 7,7'-(nonane-l,9-diylbis(azanediyl))bis(3-amino-2,8-dimethyl-5- phenylphenazin-5-ium) chloride and 3-amino-7-(9-(7-amino-2,8-dimethyl-5-phenylphenazin-5- ium-3-ylamino)nonylamino)-2,6-dimethyl-5-phenylphenazin-5-ium chloride: [1201] To a stirred solution of mixture of 7,7'-(2,2, 18, 18-tetramethyl-4, 16-dioxo~3, 17-dioxa- 5, 15-diazanonadecane-5, 15-diyl)bis(3-(tert-butoxycarbonylamino)-2,8-dimethyl-5- phenylphenazin -5-ium) chloride and 7-(tert-butoxycarbonyl(9-(tert-butoxycarbonyl(7-(tert- butoxycarbonyl amino)-2,8-dimethyl-5-phenylphenazin-5-iurn-3-yl)amino)nonyl)amino)-3-(tert- butoxy carbonylamino)-2,6-dimethyl-5-phenylphenazin-5-ium chloride (400 mg, 0.32 mmol) in 5 mL of DCM was added TFA (2 mL) at 0°C dropwise and stirred at RT for 12 hrs. The reaction was monitored by TLC and LCMS. After completion of reaction, solvent was removed under reduced pressure to dryness to obtained crude product which was purified by reverse phase HPLC to afford two peaks of same mass. Both peaks were then treated separately with
Methanolic HC1 and dried, then washed with water and dried again to afford the desired products. Compound 22: 35 mg. Compound 23 : 5 mg. 'H NMR Compound 22: (DMSO-d6): δ (ppm): 7.90-7.78 (m, 10H), 7.75-7.70 (m, 3H), 7.65-7.55 (m, 7H), 6.02 (s, 2H), 5.58 (s, 2H), 2.98 (m, 41 IX 2.35 (s, 6 H), 2.33 (s, 6H), 1.40-1.30 (m, 4H), 1.20-1.03 (m, 10! 1 ). Compound 23 : (DMSO-d6): δ (ppm): 7,95 (d, H i), 7.90-7.60 (m, 13H17.60-7.38 (m, 3H), 6, 15 (s, 1H), 6,0 (s, 1H), 5.54 (s, 1H), 3.42 (m, 2H), 2.98 (m, 2H), 2.30 (m, 9 H), 1.60 (m, 2H), 1.40 (s, 3H), 1.38- 1.20 (m, 8! I 1.18-1 ,02 fm.
Synthesis of {3-amino-2,8-dimethyl-5-phenyl-7-[(6-{[3,5,7-tris({6-[(7-amino-5-chloranuide-2, dimethyl-5-phenyl-5λ6, 10-phenazin-5-ylium-3-yl)amino]hexyl}carbamoyl)adamantan-l - yl]formamido}hexyl)amino]-5 b, 10-phenazin-5-ylium-5-e}chloranuide
Figure imgf000379_0001
Figure imgf000380_0001
Figure imgf000381_0001
Step-1 Synthesis of 2~(6-iodohexyl)isoindoline-l,3~dione
[1202] To a suspension of potassium l,3-dioxoisoindoiin-2-ide (5 g, 27 mmol) in DMF (250 mL) was added 1 ,6-diiodohexane (22,83 g, 67,5 mmol) dropwise and heated at 85 °C for 2 h. The reaction mixture was monitored with LCMS. The reaction mixture was diluted with cold water and extracted with diethyl ether (2x300 mL), and the combined organic layer was washed with water (3x250 mL) and brine (250 mL). The organic layer dried over sodium sulfate and concentrated under reduced pressure to obtain a crude product which was purified by column chromatography with 10% EtOAc in hexane as eluent to afford 8.5 g of 2-(6- iodohexyl)isoindoline-l,3-dione.
Step-2 Synthesis of 3-(tert-butoxycarbonyl(6-(l,3-dioxoisoindolin-2-yl)hexyl)amino)-7-(tert- butoxycarbonylamino)-2,8-dimethyl-5-phenylphenazin-5-ium chloride
[1203] To a solution of 3 ,7-bis(tert-butoxycarbonylamino)-2,8-dimethyl-5-phenylphenazin-5- ium chloride (6 g, 10.90 mmol) in DMF (80 mL) at RT was added cesium carbonate (8.85 g, 27,25 mmol) portion-wise and stirred for 15 min. Then, 2-(6-iodohexyl)isoindoline-l ,3-dione (5.06 g, 14.18 mmol) was dissolved in DMF (40 mL) and added dropwise at 0° C. The reaction mixture was stirred at RT for 16 h. The reaction mixture was monitored by LCMS and diluted with cold water and extracted with EtOAc (2x200 mL). The combined organic layer washed with brine (4x100 mL), dried over sodium sulfate, and concentrated under reduced pressure. The crude product was purified by column chromatography (Neutral alumina eluent 40% EtOAc in hexane to afford 6.5 g of 3-(tert-butoxycarbonyl(6-(l,3-dioxoisoindolin-2-yl)hexyl)amino)-7- (tert-butoxycarbonylamino)-2,8-dimethyl-5-phenylphenazin-5-ium chloride.
Step-3 Synthesis of 3-((6-aminohexyl)(tert-butoxycarbonyl)amino)-7-(tert- butoxycarbonylamino)-2,8-dimethyl-5-phenylphenazin-5-ium chloride
[1204] To a solution of 3-(tert-butoxycarbonyl(6-(l,3-dioxoisoindolin-2-yl)hexyl)amino)-7-(tert- butoxycarbonylamino)-2,8-dimethyl-5-phenylphenazin-5-ium chloride (4 g, 5.12 mmol) in ethanol (250 mL) was added hydrazine hydrate (5.36 g, 107.38 mmol) and heated to reflux at 85 °C for 1 h. The reaction mixture was monitored by LCMS and then the reaction mixture was concentrated and the residue dissolved in diethyl ether and filtered. The filtrate was concentrated under reduced pressure and the crude product was purified by column chromatography (Neutral alumina eluent 4 % MeOH in DCM) to afford 1.2 g of 3-((6-aminohexyl)(tert- butoxycarbonyl)amino)-7-(tert-butoxycarbonylamino)-2,8-dimethyl-5-phenylphenazin-5-ium chloride.
Step-4:- Synthesis of 3-[(tert-butoxycarbonyl)(6-{[3,5 ,7-tris({6-[(tert-butoxycarbonyl)({7- [(tert-butoxycarbonyl)amino]-2,8-dimethy^
carbamoyl)adamantan-l -yl]formamido}hexyl)amino]-7-[(tert-butoxycarbonyl)ami
hyl-5-pheny]-5 a-phenazin-5-ylium tetrachloride
[1205] To a solution of adamantine-l,3,5,7-tetracarboxylic acid (30 mg, 0.0961 mmol) in DMF (6 mL) were added EDC.HC1 (137 mg, 0721 mmol) and HOBt (97 mg, 0.721 mmol) and the mixture stirred at RT for 15 min. Then 3-((6-aminohexyl)(tert-butoxycarbonyl)amino)-7-(tert- butoxycarbonylamino)-2,8-dimethyl-5-phenylphenazin-5-ium chloride (280 mg, 0.432 mmol) and DIPEA (0.23 mL, 1.345 mmol) were added portion-wise and the mixture stirred at RT for 16 h. The reaction mixture was monitored by LCMS and diluted with water. The precipitate was filtered and washed with water. The residue was dissolved in DCM (75 mL), dried over sodium sulfate and concentrated under reduced pressure to obtain the crude product, which was purified by column chromatography (Neutral alumina eluent 5 % MeOH in DCM) to afford 120 mg of BOC protected tetramer of adamantine.
Step-5:- Synthesis of 2-{3-amino-2,8-dimethyl-7-[(6-{[3,5,7-tris({6-[(7-amino-2,8-dimethyl-5- phenyl-5λ5-phenazin-5-ylium-3-yl)amino]hexyl}carbamoyl)adamantan-l-yl]formamido}hexyl)a mino]-5 5-phenazin-5-ylium-5-yl}benzen-l-ide trichloride hydrochloride [1206] To the BOC protected tetramer of adamantine from Step-4 (120 mg, 0.046 mmol) in DCM (4 mL) at 0° C was added TFA (0.1 mL) dropwise and the mixture stirred at RT for 16 h. The reaction mixture was monitored by LCMS and sol vent was removed and the crude product was purified by HPLC. The product was treated with Methanolic HCl (4x20 mL) and
concentrated each time, then triturated with water (5 mL), filtered, and washed with water (20 mL). The residue was dried under iyophiiization to afford 25 mg of desired product. 1H NMR (DMSO): δ (ppm): 7.60-7.90 (m, 44 I f ), 6.02 (s, 4 H), 5.45 (s, I H), 2.90-3.0 (m, 16 H), 2.30 (s, 12H), 2,25 (s, 12H), 1.76 (s, 12H), 1.30-1 ,36 (m, 16H), 1.05-1.10 (m, 16H).
LCMS: 1897.10,M/4=474.6, M/3=632.6, M/2=948.5.
EXAMPLE 15. Synthesis of Compound 25
Synthesis of {3-amino-2,8-dimethyl-5-phenyl-7-[(3-{[3,5,7-tris({3-[(7-amino-5-chioranuide--2,8- dimethyl-5-phenyi-5 6, 10-phenazin-5-yliuni-3-yl)amino]propyl}carbamoyl)adamantan-l- yl]formamido}propyi)amino]-5 .fa, 10-phenazin-5-ylium-5-e}chloranuide
Figure imgf000383_0001
Figure imgf000384_0001
Step-1 : Synthesis of 2-(3-iodopropyl) isoindoline-l ,3-dione
[1207] To a suspension of potassium l ,3-dioxoisoindolin-2-ide (3 g, 16,2 mmol) in DMF ( 150 mL) was added 1,3-diiodopropane (4,2 mL, 36.4 mmol) dropwise and heated at 85°C for 2 h. The reaction mixture was monitored by LCMS, The reaction mixture was diluted with cold water and extracted with diethyl ether (2x250 mL). The combined organic layer was washed with water (3x200 mL) and brine (250 mL). The organic layer was dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by chromatography with 10% EtOAc in hexane as eluent to afford 3 g of 2-(3-iodopropyI) isoindoline-l,3-dione. Step-2: Synthesis of 3-(tert-butoxycarbonyl(3-( 1 ,3-dioxoisoindolin-2-yl)propyl)amino)-7-(tert- butoxycarbonylamino)-2,8-dimethyl-5-phenylphenazin-5-ium chloride
11208] To a solution of 3, 7-bis(tert-butoxycarbonylamino)-2,8-dimethyl-5-phenylphenazin-5- ium chloride (4 g, 7,272 rnrnoi) in DMF (50 mL) at RT was added cesium carbonate (5,9 g, 18.1 mmol) portion-wise and stirred for 15 min. 2-(3-Iodopropyl)isoindoline-l,3-dione (2.97 g, 9.45 mol) was dissolved in DMF (10 mL) and added dropwise at 0°C, The reaction mixture was stirred at RT for 16 h. The reaction mixture was monitored by LCMS and then diluted with cold water. The precipitate was filtered, and washed with water. The precipitate was dissolved in DCM (150 mL) and dried over sodium sulfate, and concentrated under reduced pressure to give a crude product that was purified by column chromatography (neutral alumina: eluent 2 % MeOH in DCM) to afford 3 g of 3-(tert-butoxycarbonyl(3-(l,3-dioxoiso indolin-2-yl)propyl)amino)-7- (tert-butoxycarbonylamino)-2,8-dimethyl-5-phenylphenazin-5-ium chloride.
Step-3 : Synthesis of 3-((3-aminopropyl)(tert-butoxycarbonyl)amino)-7-(tert- butoxycarbonylamino)-2,8-dimethyl-5-phenylphenazin-5-ium chloride
[1209] To a solution of 3-(tert-butoxycarbonyl(3-(l,3-dioxoisoindolin-2-yl)propyl)amino)-7- (tert-butoxycarbonylamino)-2,8-dimethyl-5-phenylphenazin-5-ium chloride (3 g, 4.06 mmol) in ethanol (200 mL) was added hydrazine hydrate (3.9 mL, 81.3 mmol) and heated to reflux at 85°C for l h. The reaction mixture was monitored by LCMS, and then the reaction mixture was concentrated and the residue dissolved in diethyl ether and filtered. The filtrate was concentrated under reduced pressure and the crude product was purified by column chromatography (neutral alumina eluent 4 % MeOH in DCM) to afford 1 g of 3-((3-aminopropyl)(tert- butoxycarbonyl)amino)-7-(tert-butoxycarbonylamino)-2,8-dimethyl-5-phenylphenazin-5-ium chloride.
Step-4: Synthesis of BOC protected tetramer of adamantane
11210] To a solution of adamantane 1,3,5,7-tetracarboxylic acid (30 mg, 0.0961 mmol ) in DMT (6 mL) were added EDC.HC1 (137 mg, 0721 mmol) and HOBT (97 mg, 0.721 mmol) and the mixture stirred at RT for 15 min. Then 3-((3-aminopropyl)(tert-butoxycarbonyl)amino)-7-(tert- butoxycarbonylamino)-2,8-dimethyl-5-phenylphenazin-5-ium chloride (263 mg, 0,432 mole) was added portion-wise and the mixture stirred at RT for 16 h. The reaction mixture was monitored by LCMS, and then diluted with water. The precipitate was filtered and washed with water. The residue was dissolved in DCM (75 mL), dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (Neutral alumina eluent 3 % MeOH in DCM) to afford 125 mg of BOC protected tetramer of adamantane.
Step-5: Synthesis of {3-amino-2,8-dimethyl-5-phenyl-7-[(3-{[3,5,7-tris({3-[(7-amino-5- chloranuide-2,8-dimethyl-5-phenyi-5 6, 10-phenazin~5-ylium~3~
yl)amino]propyl}carbamoyl)adamantan-l-yl]forma^
y 1 i um - 5 - e } chl or an ui d e
[1211] To the BOC protected tetramer of adamantane from Step-4 (125 mg, 0.046 mmol) in DCM (4 mL) at 0° C was added TFA (0.5 mL) dropwise and the mixture allowed to stir at RT for 16 h. The reaction mixture was monitored by LCMS and solvent was concentrated to obtain a crude product that was purified by reverse phase HPLC to obtain desired product. This product was treated with methanolic HCl (4x20 mL), concentrated each time, then triturated with water (5 mL), filtered and washed with water (20 mL). The residue was dried by lyophilization to afford 25 mg of {3-amino-2,8-dimethyl-5-phenyl-7-[(3-{[3,5,7-tris({3-[(7-amino-5-chloranuide- 2,8~dimethyl-5-phenyl-5 6, 10-phenazin~5-ylium-3~yl)amino]propyl} carbamoyl)adamantan-l- yl]formamido}propyl)amino]-5 D, 10-phenazin-5-ylium-5-e}chloranuide. Ή NMR (DMSO): δ (ppm): 7.60-7.90 (m, 44H), 6.0 (s, 4H), 5,45 (s, 4H), 2,90-3 ,0 (m, 16H), 2.30 (s, 12H), 2.25 (s, 12H), 1.76 (s, 12H), 1.65-1.75 (m, 8H). LCMS: 1728.9, M/4=432.8, M/3=576.5, M/2=864.3.
EXAMPLE 16. Synthesis of Compound 26
Synthesis of (3-amir!O-7-{[6-({6-[5-({6-[(7-amino-5-chloranuide-2,8-dimethyl-5-pher!yl-5 6,10- phenazin-5-ylium-3-yl)amino]hexyl}carbamoyl)pyridin-2-yl]pyridin-3- yl}formamido)hexyl]amino}-2,8-dimethyl-5-^^
Figure imgf000386_0001
Step-1
Figure imgf000387_0001
Step-1 : Synthesis of tert-butyl N-[8-(tert-butoxycarbonylamino)-3,7-dimethyl-10-phenyl- phenazin-10-ium-2-yl]-N-[6-[[6-[5-[6-[tert-butoxycarbonyl-[8-(tert-butoxycarbonylamino)-3,7- dimethyl- 10-phenyl-phenazin-10-ium-2-yl]amino]hexylcarbamoyl]-2-pyridyl]pyridine-3- carbonyl]amino]hexyl]carbamate dichlori de
[1212] To a suspension of 2,2'-bipyridine-5,5'-dicarboxylic acid (50 mg, 0,204 mmol) in DMF (5 ffiL) were added EDC.HCi (155 mg, 0.816 mmol) and HOBt (109 mg, 0.816 mmol) and the mixture stirred at RT for 20 min. Then 3-((6-aminohexyl)(tert-butoxycarbonyl)amino)-7-(tert- butoxycarbonylamino)-2,8-dimethyl-5-phenylphenazin-5-ium chloride (293 mg, 0.450 mmol) and DDPEA (0.35 mL, 2.04 mmol) were added portion-wise and the mixture stirred at RT for 12 h. The reaction mixture was monitored by LCMS, and then diluted with water, extracted with EtOAc (2x25 mL). The combined organic layer was washed with brine (4x25 mL), dried over sodium sulfate, and concentrated under reduced pressure. The crude product was purified by column chromatography (neutral alumina eiuent 5 % MeOH in DCM) to afford 125 mg of BOC protected dimer.
Step-2: Synthesis of N-[6-[(8-amino-3,7-dimethyl-10-phenyl-phenazin-10-ium-2- yl)amino]hexyl]-6-[5-[6-[(8-amino-3,7-dimethyl-10-phenyl-phenazin-10-ium-2- yl)amino]hexylcarbamoyl]-2-pyridyl]pyridine-3-carboxamide dichlori de
[1213] To the BOC protected dimer from Step-1 (90 mg, 0.0596 mmol) in DCM (5 mL) at 0° C was added TFA (0.4 mL) dropwise and the mixture stirred at RT for 12 h. The reaction mixture was monitored by LCMS. The solvent was evaporated and the crude product purified by HPLC to obtain the desired product, which was treated with methanoiic HCl (4x15 mL), concentrated each time, then triturated with water (5 mL), filtered and washed with water (20 mL). The residue was dried by lyophilization to afford 15 mg of title compound. 1H NMR (DMSO): δ (ppm): 9.10 (s, 2H), 8.83 (t, 2 H), 8.43 (d,2 H), 8.38 (d, 2H), 7.90-7.75 (m, 10 H) 7.62-7.72 (m, 2 H), 7,60 (d, 4 H), 7.60-7.50 (m,2 H), 6.0 (s, 2H), 5.50 (s, 2H), 3.26 ( m. 4H), 2.99 (m, 4H), 2,35 (s, 6H), 2.33 (s, 6H), 1 .50- 1 .42 (m, 4H), 1.40-1.30 (m, 4H), 1.20-1.05 (m, 8H). LCMS: 1036.56, M/3 346 3, M/2 5 1 8 Q.
EXAMPLE 17. Synthesis of Compound 27
Synthesis of (3-amino-7-[(6-{ [3-( {6-[(7-amino-5-chloranuide-2,8-dimethyl-5-phenyl-5 6, 10- phenazin-5-ylium-3-yl)amino]hexyl}carbamoyl)adamantan- l-yl]formamido}hexyl)amino]-2,8- dimethyl~5-phenyl-5)v6, 10-phenazin-5-ylium-5-e}chloranuide
Figure imgf000388_0001
Step-2
Figure imgf000389_0001
Step-1 : Synthesis of tert-butyl N-[8-(tert-butoxycarbonylamino)-3,7-dimethyl-10-phenyl- phenazin-10-ium-2-yl]-N-[6-[[3-[6-[teit-butoxycarbonyl-[8-(tert-butoxycarbonylamino)-3,7- dime1hyl-10-phenyl-phenazin-10-ium-2-yl]amino]hexylcarbamoyl]adamantane-l- carb ony 1 ] amino] hexy 1 ] carb am ate dichl ori d e
[1214] To a solution of 1,3-adamantanedicarboxylic acid (40 mg, 0.178 mmol) in DMF (65 mL) were added EDC.HC1 ( 19 mg, 0,623 mmol ) and HOBt (84 mg, 0.623 mmol) and the mixture stirred at RT for 15 min. Then 3-((6-aminohexyl)(tert-butoxycarbonyl)amino)-7-(tert- butoxycarbonylamino)-2,8-dimethyl-5-phenylphenazin-5-ium chloride (255 mg, 0.392 mmol) and DIPEA (0.22 mL, 1.335 mmol) were added portion-wise and the mixture stirred at RT for 16 h. The reaction mixture was monitored by LCMS and diluted with water and extracted with EtOAc (2x25 mL). The combined organic layer was washed with water (2x20 mL) and brine, dried over sodium sulfate, and concentrated under reduced pressure to obtain the crude product, which was purified by column chromatography (Neutral alumina eluent 4 % MeOH in DCM) to afford 150 mg of tert-butyl N-[8-(tert-butoxycarbonylamino)-3,7-dimethyl-10-phenyl-phenazin- 10-ium-2-yl]-N-[6-[[3-[6-[tert-buto
phenyl -phenazin- 10-ium-2-yl]amino]hexyl carbamoyljadamantane- 1 - carbonyl]amino]hexyl]carbamate dichl ori de. Step-2: Synthesis of Nl , 3-bis[6-[(8-amino-3,7-dimethyl-10-phenyl-phenazin-10-ium-2- yl)amino]hexyl]adamantane-l,3-dicarboxamide dichloride
11215] To the compound from Step-1 (150 mg, 0.100 mmol) in DCM (3 mL) at 0° C was added TFA (0.3 mL) dropwise and the mixture stirred at RT for 16 h. The reaction mixture was monitored by LCMS, then the solvent was concentrated and the cmde product was purified by HPLC to obtain pure product. This was treated with methanolic HC1 (4x15 mL), concentrated each time, then triturated with water (5 mL), filtered, and washed with water (10 mL). The residue was vacuum dried under lyophilization to afford 20 mg of Nl, N3-bis[6-[(8-amino-3,7- dimethyl-10-phenyl-phenazin-10-ium-2-yl)am
dichloride. 1H MR (DMSO): δ (ppm): 7.80-7.90 (m, 10 H), 7.60 (d, 6H), 7,50-7,60 (m, 2H), 7.40-7.45 (m, 2H), 6.02 (s, 2H), 5.50 (s, 2H), 2.98-3.04 (m, 8H), 2,30 (s, 6H), 2.28 (s, 6H), 2,04 (m, 2H), 1.8 Cm. 2H), 1 ,70-1 ,75 (m, 8H), 1.55-1.60 (m, 2H), 1.25-1.40 (m, lOH), 1.05 (m, 6H). LCMS: 1016.6 (M), 508,6 (M/2).
EXAMPLE 18. Synthesis of Compounds 28 and 29
Synthesis of 7,7'-(dodecane-l, 12-diylbis(azanediyl))bis(3-amino-2,8-dimethyl-5- phenylphenazin-5-ium) chloride and 3-amino-7-(12-(7-amino-2,8-dimethyl-5-phenylphenazin-5 ium-3-ylamino)dodecylamino)-2,6-dimethyl-5-phenylphenazin-5-ium chloride
Figure imgf000391_0001
Step-1 : Synthesi s of 7,7'-(2,2,21 ,21 -tetramethyl-4, 19-dioxo-3,20-di oxa-5, 18-di azadocosane- 5, 18-diyl)bis(3-(tert-butoxycarbonylamino)-2,8-dimethyl-5-phenylphenazin-5-ium) chloride and 7-(tert-butoxycarbonyl(12-(tert-butoxycarbonyl(7-(tert-butoxycarbonylamino)-2,8-dimethyl-5- phenylphenazin-5-ium-3-yl)amino)dodecyl)amino)-3-(tert-butoxycarbonylamino)-2,6-dimethyl- 5-phenylphenazin-5-ium chloride
[1216] To a stirred solution of a mixture of 3,7-bis(tert-butoxycarbonylamino)-2,8-dimethyl-5- phenylphenazin-5-ium chloride and 3,7-bis(tert-butoxycarbonylamino)-2,6-dimethyl-5- phenylphenazin-5-ium chloride (1.0 g, 1.81 mmol) in 15 mL of DMF was added cesium carbonate (1 .48 g, 4.54 mmol) and the mixture stirred at RT for 15 rain. The reaction mixture was then cooled to 0°C and to it was added 1, 12-dibromododecane (328 mg, 0.99 mmol, diluted with 1 mL of DMF) drop wise. The reaction mixture was then stirred at RT for 12 h. The reaction was monitored by TLC and LCMS. After completion of reaction, the mixture was diluted with ice-cold water and filtered. The solid residue obtained after filtration was dissolved in diethyl ether (200 mL) and washed with brine solution (3x50 mL). The ether layer was then dried over anhydrous sodium sulfate, and concentrated under reduced pressure to afford a crude product which was purified by column chromatography (neutral alumina, eluent 0-20% EtOAc in hexane) to afford the desired product (mixture of 2 products of same mass) as a dark brown solid (500 mg).
Step-2: Synthesis of 7,7'-(dodecane-l ,12-diylbis(azanediyl))bis(3-amino-2,8-dimethyl-5- phenylphenazin-5-ium) chloride and 3-amino-7-(12-(7-amino-2,8-dimethyl-5-phenylphenazin-5- ium-3-ylamino)dodecylarnino)-2,6-dimethyl-5-phenylphenazin-5-ium chloride:
[1217] To a stirred solution of mixture of 7,7'-(2,2,21,21-tetramethyl-4, 19-dioxo-3,20-dioxa- 5,18-diazadocosane-5, 8-diyl)bis(3-(tert-butoxycarbonylamino)-2,8-dimethyl-5-phenylphenazin- 5-ium) chloride and 7-(tert-butoxycarbonyl(12-(tert-butoxycarbonyl(7-(tert-butoxycarbonyl amino)-2,8-dimethyl-5-phenylphenazin-5-ium-3-yl)amino)dodecyl)amino)-3-(tert-butoxy carbonylamino)-2,6-dimethyl-5-phenylphenazin-5-ium chloride (500 mg, 0.39 mmol) in 5 mL of DCM was added TFA (2 mL) at 0°C dropwise and stirred at RT for 12 h. The reaction was monitored by TLC and LCMS. After completion of reaction, the solvent was removed under reduced pressure to dryness to obtain a crude product which was purified by HPLC to afford two peaks of the same mass. Both peaks were then treated separately with Methanolic HC1 and dried and then washed with water, and dried again to afford the desired products (Compound 28: 35 mg and Compound 29: 55 mg). Compound 28: lH NMR (DMSO-d6): δ (ppm): 7.90-7.78 (m, 10H), 7.75-7.70 (m, 3H), 7,65-7,55 (m, 7H), 6.02 (s, 2H), 5.58(s, 2H), 2.98 (m, 4H), 2.35 (s, 6 H), 2,33 (s, 6H), 1.40-1 ,30 (m, 4H), 1.25-1.20 (bs, 10H), 1 .20-1 .05 (m, 6H). Compound 29: lH NMR (DMSO-d6): δ (ppm): 7.95 (d, IH), 7.90-7.60 (m, 15H), 7.60-7.38 (m, 3H), 6.15 (s, 1H), 6.0 (s, 1 1 1 ), 5.54 (s, 1 1 1 ), 3.42 (m, 2H), 2.98 (rn, 2H), 2.30 (m, 9 1 1 ).. 1.60 (m, 2H), 1.40 (s, 3H), 1 .38- 1 .20 (m, 14H), 1.18-1.02 (m, 4H).
EXAMPLE 19. Synthesis of Compounds 4 and 31
Synthesis of 7,7'-(octane-l ,8-diylbis(azanediyl))bis(3-amino-2,8-dimethyl-5-phenylphenazin-5- ium) chloride & 3-amino-7-(8-(7-amino-2,8-dimethyl-5-phenylphenazin-5-ium-3-ylamino) octy 1 am i n o)- 2, 6-di m ethyl - 5 -ph eny 1 ph en azi n- 5 -i um chl ori de
Figure imgf000393_0001
Figure imgf000393_0002
Figure imgf000394_0001
Step-1 : Synthesis of 3,7-bis(tert-butoxycarbonylamino)-2,8-dimethyl-5-phenylphenazin-5-ium chloride and 3,7-bis(tert-butoxycarbonylamino)-2,6-dimethyl-5-phenylphenazin-5-ium chloride.
[1218] To a stirred solution of Safranin-0 (10.0 g, 28,57 mmol) in 100 mL of DMF was added sodium hydride (3.42 g, 85.71 mmol) portion-wise at 0°C. After addition, the reaction mixture was stirred at RT for 15 min. Boc anhydride (12.45 g, 57.14 mmol, diluted with 15 mL of DMF) was added dropwise into the reaction mixture and stirred at RT for 2h. The reaction was monitored by TLC and LCMS, After completion of reaction, the mixture was quenched using MeOH (30 mL), and concentrated under reduced pressure to obtain the crude product which was purified by column chromatography (neutral alumina, eluent 25% DCM in hexane to 100% DCM) to afford the desired products (a mixture of two products of the same mass) as a dark brown solid (5.0 g).
Step-2 : Synthesi s of 7,7'~(2,2, 17, 17-tetramethyl-4, 15-dioxo-3, 16-dioxa-5, 14-diazaoetadecane- 5,14-diyl)bis(3-(tert-butoxycarbonylamino)-2,8-dimethyl-5-phenylphenazin-5-ium) chloride and 7-(tert-butoxycarbonyl(8-(tert-butoxycarbonyl(7-(tert-butoxycarbonylamino)-2,8-dimethyl-5- phenylphenazin-5-ium-3-yl)amino)ocryl)amino)-3-(te^
phenylphenazin-5-ium chloride.
[1219] To a stirred solution of a mixture of 3,7-bis(tert-butoxycarbonylamino)-2,8-dimethyl-5- phenylphenazin-5-ium chloride and 3,7-bis(tert-butoxycarbonylamino)-2,6-dimethyl-5- phenyfphenazin-5-ium chloride (5.0 g, 9.07 mmol) in 60 mL of DMF was added cesium carbonate (8.87 g, 27.22 mmol) and stirred at RT for 15 min. The reaction mixture was cooled to 0°C and to it was added 1,8-diiodooctane (2.05 g, 5.62 mmol, diluted with 5 mL of DMF) dropwise. The reaction mixture was stirred at RT for 12 h. The reaction was monitored by TLC and LCMS. After completion of reaction, the mixture was diluted with ice-cold water and filtered. The solid residue was dissolved in diethyl ether (250 mL) and washed with brine solution (3x50 mL). The ether layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure to afford the crude product which was purified by column
chromatography (neutral alumina, eluent 0-40% EtOAc in hexane) to afford the desired product (mixture of 2 products of same mass) as a dark brown solid (3 g).
Step-3 : Synthesis of 7,7'-(octane-l ,8-diylbis(azanediyl))bis(3-amino-2,8-dimethyl-5- phenylphenazin-5-ium) chloride and 3-amino-7-(8-(7-amino-2,8-dimethyl-5-phenylphenazin-5- ium-3-ylamino)octylamino)-2,6-dimethyl-5-phenylphenazin-5-ium chloride.
[1220] To a stirred solution of a mixture of 7,7'-(2,2, 1.7,17-tetramethyl-4, 15-dioxo-3, 16-dioxa- 5,14-diazaoctadecane-5, 14-diyl)bis(3-(tert-butoxycarbonylamino)-2,8-dimethyl-5- phenylphenazin-5-ium) chloride and 7-(tert-butoxycarbonyl(8-(tert-butoxycarbonyl(7-(tert- butoxycarbonyl amino)-2,8-dimethyl-5-phenylphenazin-5-ium-3-yl)amino)octyl)amino)-3-(tert- butoxy carbonylamino)-2,6-dimethyl-5-phenylphenazin-5-ium chloride (2.5 g, 2.06 mmol) in 25 mL of DCM was added TFA (10 mL) at 0°C dropwise and the mixture stirred at RT for 12 h. The reaction was monitored by TLC and LCMS. After completion of reaction, the solvent was removed under reduced pressure to dryness to obtain a crude product (2 g mixture of two compounds). 400 mg of crude product was purified by reverse phase HPLC to afford two peaks of the same mass. Both peaks were then treated separately with methanolic HCl and dried, and then washed with water and dried again to afford both regioisomeric products.
EXAMPLE PL Synthesis of Compounds 2, 3, 5, and 7-17
[1221] Compounds 2, 3, 5 and 7-17 can be synthesized using the conditions provided in the Examples presented above using appropriate starting materials.
Example Bl. Isolation and Culture of MSCs from Rat Bone Marrow
[1222] A protocol based on Soleimani & Nadri, Nature Protocols 4, 102-106, 2009, was used to isolate MSCs from rat bone marrow and culture the MSCs.
[1223] Sprague Dawley rats weighing between 250-300 g were rinsed in 70% ethanol. An incision was made around the perimeter of the hind limbs where they are attach to the tnmk. Skin was removed by pulling toward the foot, which was cut at the ankle bone to eliminate further contact of the hind limb with the animal's fur, which is a source of contaminating bacteria. The hind limbs were dissected from the trunk of the body by cutting along the spinal cord with care not to damage the femur.
[1224] Each hind limb was bisected by cutting through the knee joint. Muscle and connective tissue were removed from both the tibia and the femur by scraping the diaphysis of the bone clean then pulling the tissue toward the ends of the bone. After cleaning, the bones were stored on ice in IX Hank's balanced salt solution (BBSS), pH: 7.2 (GIBCO®, Cat: 14185-012) until bone marrow was harvested.
[1225] Bone marrow was harvested in a hood using sterile technique. Bones were placed in ethanol for 5 minutes and then transferred to a 10 cm culture dish (NUNC™) containing
"complete medium," which is MESENPRO RS™ medium (GIBCO®, Cat: 12747-010) supplemented with 2 niM L-glutamine, 1% penicillin-streptomycin (10.000 U/niL, GIBCO®, Cat: 15 40-122), 15% inactivated fetal bovine serum (FBS; GIBCO®, Cat: 16000-044), and I X MEM NEAA Solution (Minimal Essential Medium, Non-Essential Amino Acids; GIBCO®, Cat: 1 1 140-050).
[1226] The ends of the tibia and femur were cut just below the end of the marrow cavity using fine scissors. A 21 -gauge needle attached to a 5-10 mL syringe containing cold complete medium was inserted into spongy bone exposed by removal of the growth plate. The marrow plug was flushed out of the cut end of the bone with medium and collected in a 50 mL tube (THERMO SCIENTIFIC™) on ice.
[1227] The cell suspension was centrifuged at 400 x g for 5 minutes at RT. At this point the pellet is not very compact so the supernatant was removed carefully. The cells were resuspended in fresh medium, and the suspension was filtered using a 70 um filter mesh (FALCON®, Cat:352350) to remove any bone spicules or muscle and cell clumps.
[1228] A sample of the cell suspension was diluted 1/50 and counted in a hemocytometer.
Viability was determined by Trypan Blue exclusion (0.4%, GIBCO®, Cat: 15250-061).
Typically between 400 and 500 million cells were obtained per rat.
[1229] Bone marrow cells were cultured in a 10 cm culture dish in 5 mL of complete medium at a density of 25xl06 cells per plate at 37 °C with 5% C02 in a humidified chamber without disturbing them.
[1230] After 4 hours, non-adherent cells that accumulated on the surface of the dish were removed by washing twice with PBS-EDTA, which is IX phosphate-buffered saline IX, pH 7.4 (GIBCO®, Cat: 70011-044) containing with 5 mM EDTA (Invitrogen, Cat: 15576-028) twice, which was then replaced with 10 raL of fresh complete medium. Ever}' 3-4 days, adherent cells were washed vigorously twice with PBS-EDTA, and fresh medium was added.
[1231] Once cells reach about 90% confluence, they are passaged using trypsin, washed in IX PBS, and re-seeded at a density of 5 x 106 cells per 10 cm culture dish. When cells in passage 3 are about 90% confluent, cells are trypsinized with 0.025% trypsin-EDTA (Gibco, 15090-046) for 8 min at 37°C and 5% C02 and washed with PBS IX. Two hundred thousand living cells were placed in a polystyrene round bottom tube (BD Falcon, 352052). Cells were washed with Flow Cytometry Staining Buffer (1 % w/v BSA [Rockland, BSA50], 0.1 % w/v Sodium Azide [Sigma-Aldrich, 438456] in PBS IX) and centrifuged at 400 x g for 5 min at room temperature. Subsequently cells were resuspended in 100 (u.L of Flow Cytometry Staining Buffer and incubated with primary antibodies for 20 min at 4°C in the dark (0.25 μg/mL CD45 FITC [BD Bioscience, 561867], 0.2 ,ug/mL CD90 PE-Cy7 [Biolegend, 202518], 0.25 fig/mL CD29 PE [BD Bioscience, 562154], 0.25 μg/mL CDl lb PE-Cy7 [BD Bioscience, 562222], 0.25 ,ug/mL CD54 PE [Biolegend, 202405], 0,25 ,ug/mL IgGl FITC [BD Bioscience, 552811] and 0.25 ^ig/mL IgM PE [BD Bioscience, 553943]). Cells were washed and resuspended in 500 μΕ of Flow Cytometry Staining Buffer for analysis in MACSQuant® Analyzer 10 (Miltenyi), Characterization of rat- derived MSCs was based on Zhang & Chan, J Vis Exp. 2010 Mar 22;(37), including CD29+ and CDl lb" markers. The results are shown in Table 2. These results demonstrate that >90% of the obtained cells are MSCs,
Table 2. Phenotypic characterization of rat-derived MSCs at passage 3
Figure imgf000397_0001
% of MSCs (CD45-, CDl l b-, CD29+, CD54+, CD90+) = 92%
Example B2„ Formation of Raji Cell Pellets in the Presence of Compound 20
[1232] 1()6 Raji cells were placed in 1.5 niL tubes in a final volume of 500 ,L PBS and incubated with 1 uM or 10 uM of Compound 20 for 1, 5, 15, or 30 min. After the incubation, the cells were washed by adding 500 p.L of PBS. Cells were centrifuged at 500xg for 5 min to form a pellet, and the pellet was gently released from the bottom of the tube with 100 μΕ of PBS. [1233] The results are shown in FIG. 1. These results demonstrate that Raji cells form pellets after incubation with 10 μΜ Compound 20 after as little as 1 minute.
Example B3, Stability of Raji Cell Pellets After Incubation with Compound 20
[1234] 1.5 xl0° Raji cells were placed in 1.5 mL tubes in a final volume of 500 μ.Ι_ PBS, then incubated with 1 μΜ or 10 μΜ of Compound 20 for 5 min or 30 min on a shaker at RT. After the incubation, the cells were washed by adding 500 μί of PBS. Cells were centnfuged at 500xg for 5 min to form a pellet, and the pellet was gently released from the bottom of the tube with 100 uL of PBS.
[1235] To test the stability of the pellets, the pellets were placed on a flat bottom 96-well plate using a cut p OOO micropipette tip in 100 ul, final volume in PBS, The plate was shaken using lineal movement at a speed of 567 cycles per minute (cpm) in a CYTATION™ 5 imaging equipment. Images of the wells were taken by the CYTATION™ 5 using Gen 5 2.07 software.
[1236] The results are shown in FIG. 2A (30 min. incubation with Compound 20) and FIG. 2B (5 min. incubation with Compound 20). These results demonstrate that pellets formed in the presence of 10 μΜ Compound 20 for as little as 5 min. remain essentially intact after shaking for up to 5 minutes. Any pellets formed with cells incubated in PBS are not durable and cells disperse quickly within 30 seconds with the pellet fully dismantled by 5 min.
Example B4. Differentiation of Rat Bone Marrow-Derived MSCs in Pellet Cultures
[1237] This example demonstrates that 10 μΜ Compound 20 promotes chondrogenic differentiation of rat bone marrow-derived MSCs in pellet cultures incubated with chondrogenic medium.
Differentiation protocol
[1238] Rat MSCs were obtained as described in Example Bl. After reaching 90% confluence, MSCs were removed from the culture plate or flask using 2.5% trypsin (GIBCO®, Cat: 15090- 046) for 5 min. The cells were centnfuged in 15 ml tubes at 500xg for 4 min, and the supernatant was removed.
[1239] Cells were incubated at a density of 0.5-10 x 106 ceils in 500 of a 10 μΜ solution of Compound 20 in PBS for 20 min at RT on a shaker, then centnfuged in 1.5 ml tubes at 500xg for 4 min. The supernatant was removed, and the ceils were washed gently by adding 500 μΙ_ of PBS and centrifuging at 500xg for 7 min. The cells were resuspended in 500 μΐ,. of PBS and counted. [1240] 5xl()5 viable cells were placed in a 15 mL tube and centrifuged at 500xg for 7 min, then 500 uL of chondrocyte differentiation media (STEMXVIVG®, Cat N° CCM005-CM006) was added. The medium was changed even,' 2 to 3 days, maintaining the 500 uL volume, for 3 weeks. laimimofliioresceece assay
[1241] The medium was removed from the 5 mL tube and replaced with 500 L of 4% paraformaldehyde in PBS and incubated for 20 min at RT. The paraformaldehyde solution was removed, and replaced with 500 μ!, of 4% paraformaldehyde, 15% sucrose in PBS. The pellet was left in this solution overnight.
[1242] The solution was removed and replaced with 500 Τ of 4% paraformaldehyde, 30% sucrose in PBS, The pellet was left in this solution overnight or until the pellet is in the bottom of the tube.
[1243] The pellet was frozen in O.C.T™ compound (TISSUE-TE ®, Cat N° 4583), and 5 μιη sections were cut and fixed on a positively charged slide (Cell Path, Cat N° MDB-0102-54 A).
[1244] A line was drawn around the sections with a hydrophobic pen. 100-300 μΕ of blocking solution (1% BSA, 0.3% TRITON® X-100 in PBS) was placed on the sections and left for lh at room temperature. The blocking solution was removed with a micropipette. The primary antibody solution (goat anti-aggrecan Gl-IgD-G2 domain, R&D SYSTEMS™, Cat N° AF1220) was diluted 1 :20 in blocking solution, and 100-200 μΕ of the antibody solution was placed on the sections. The sections were left at 4°C overnight in a humidified box,
[1245] The primary antibody solution was removed, and the sections were washed3 times with 1 % BSA in PBS for 5 min. The lines around the sections were redrawn with the hydrophobic pen.
[1246] The secondary antibody (donkey anti-goat IgG ALEXA FLUOR® 488, LIFE
TECHNOLOGIES™, Cat N° Al 1055) was diluted 1 : 100 in blocking solution, and 100-200 μί.. of the secondary antibody solution was added to the sections. The sections were incubated in the dark for lh at RT, and the remaining steps were carried out in the dark to avoid degrading the fiuorophor. The sections were then washed 3 times with 1% BSA in PBS for 5 min, and the lines around the sections were redrawn with the hydrophobic pen.
[1247] 100-200 μΕ of a 1 :2000 dilution of DAPI in PBS were added to the sections, which were incubated for 5 min at RT. The DAPI was removed, and the sections were washed 3 times with PBS for 5 min and a 4th time with distilled water for another 5 min. After drying, 30 μΕ of Fluorescence Mounting Medium (Dako, catalog # 53023)was added to the sections, which were then covered with a coverslip and stored at 4C'C.
[1248] The results are shown in FIG 3A and FIG. 33B, These results demonstrate that 10 uM Compound 20 permits chondrogenic differentiation of rat bone marrow-derived MSCs in pellet cultures incubated with chondrogenic medium. This can be seen by the extracellular aggrecan staining in FIG. 3B.
Example B5. Chondrogenic Differentiation of Rabbit MSCs in Pellet Cultures in the
Presence of Compound 20
[1249] This example demonstrates that 10 μΜ Compound 20 promotes chondrogenic
differentiation of rabbit MSCs in pellet cultures incubated with either chondrogenic medium or basal medium.
[1250] Rabbit MSCs (Cyagen Cat N° RBXMX-01001) were cultured and incubated with 10 μΜ Compound 20 as described for the rat bone marrow-derived MSCs in Example B4. Cells were used up to passage 5 and after that were discarded. After incubation with Compound 20, some cultures were provided with basal medium (DMEM, Life Technologies Cat N° 1 1965-092) supplemented with 10% FBS (Gibco, catalog number 16000) and penicillin streptomycin (Gibco, catalog number 15140- 122) or chondrocyte differentiation media (StemXvivo Cat N° CCM005- CM006) supplemented with penicillin streptomycin. The medium was changed even,' 2 to 3 days, maintaining the 500 \ih volume, for 21 days.
[1251] The immunofluorescence assay was carried out as described in Example B4. The results are shown in FIGS. 4A-D. These results demonstrate that 10 μΜ Compound 20 permits chondrogenic differentiation of rabbit MSCs in pellet cultures incubated with chondrogenic medium and promotes chondrogenic differentiation of rabbit MSCs in pellet cultures incubated with basal medium {i.e., in the absence of TGF'P).
Example B6. Chondrogenic Differentiation of Low Density Rabbit MSC Pellet Cultures in the Presence of Compound 20
[1252] This example demonstrates that Compound 20 promotes chondrogenic differentiation of rabbit MSCs in low density pellet cultures incubated in supplemented basal medium {i.e. , in the absence of TGF-β). Rabbit MSCs were cultured as described in Example B4 except that pellets were formed using 103 MSCs. The immunofluorescence assay was carried out as descri bed in Example B4. The results are shown in FIGS. 5A-F. These results demonstrate that Compound 20 promotes chondrogenic differentiation of rabbit MSCs in low density pellet cultures. EXAMPLE B7. Targeting of Raj i Cells and Rabbit MSCs to Various Organs
[1253] The femur, cecum, heart, kidney, liver, trachea, lungs, pancreas, spleen, and a portion of the small intestine were extracted from 3 month old C57B1/6 mice and washed 3 times with PBS in 50 ml conical tubes.
[1254] Non-adherent Raji cells (10 ') were incubated in 500 iL of 10 μΜ calcein AM
(Invitrogen, Cat N° C3100MP) in PBS for 30 min on a shaker at RT. The cells were washed by adding 500 _uL PBS, centrifuging at 500g for 4 min, removing supernatant, and resuspending the cel ls in 500 μΐ, PBS. The cells were then incubated in 500 μΐ.. 10 μΜ Compound 20 in PBS or in PBS alone (control) for 30 min on a shaker at RT. The cells were washed by adding 500 μΐ. PBS, centrifuging at 500g for 4 min, removing supernatant, and resuspending cells in 1 mL PBS. The cells were then counted, and 0.5 x 106 cells were added over each organ in 1 mL of PBS in a p 8 well plate, and incubated for 30 min at RT. The organs were then gently washed in 1 mL of PBS in a new p48 well.
[1255] Rabbit mesenchymal stem ceils (rbMSCs were treated as described above, except that washing for for 2 min instead of 4 min.
[1256] Adherence of the Raji cells or MSCs to the organs was evaluated by detecting the fluorescence of calcein dye using a ChemiDoc MP Imaging System (470/530 filter) and
ImageLab software and compared to the PBS control. The results are shown in FIG. 6 (Raji cel ls) and FIG. 7 (rbMSCs).
EXAMPLE B8, Targeting of Raji Cells to Meniscus Explants
[1257] Whole menisci were extracted from 4-6 month old NZW rabbits and washed 3 times with PBS in 50 mi conical tubes. The menisci were incubated with 100 μΜ of biotin-conjugated compound 4 or biotin-conjugated compound 20 in a final volume of 1 mL in PBS or 1 mL PBS alone for 30 min at RT in a 48 well plate, then washed twice in new p48 wells with 1 mL PBS.
[1258] The menisci were incubated with 1 ug/ml of streptavidin-FITC (SA-FITC) (Thermo 21224) in a final volume of 1 mL in PBS for 30 min at RT in the dark, then washed twice in a new ρ48 well plate with 1 mL PBS. Staining of the menisci was evaluated by measuring fluorescence in FITC channel (470/530 filter) using ChemiDoc MP Imaging System and
ImageLab software. [1259] Non-adherent Raji cells (10'') were incubated with compound 4 or compound 20 as described above in Example B l . Cells were counted, and 0.5 x 106 cells were placed over the meniscus explants in 1 mL of PBS in a 48 well plate and incubated for 30 min at RT. The explants were gently washed in 1 niL of PBS in a new p48 well plate.
[1260] Cell adherence to the meniscus explants was evaluated by measuring fluorescence of calcein dye using a ChemiDoc MP Imaging System (470/530 FITC filter) and ImageLab software.
[126.1] The results are shown in FIG. 8A and FIG. SB, These results demonstrate that compounds 4 and 20 romote adherence of Raji cells to meniscus explants. Compound 6873 is a
reference compound,
Figure imgf000402_0001
EXAMPLE B9. Persistance of Compound 4 in the Knee After Intra-Articular Injection
[1262] Six- to eight-week old Sprague Dawley rats were anesthetized with 3% sevofluorane, and both right and left knees were shaved and washed. 250 ul of a solution of 10 mg/ml Compound 4 in PEG400 (Spectrum POl 10) was injected intra-articulariy through the patellar ligament on the right knees. 250 μΐ of vehicle (PEG400) was injected intra-articulariy into left knees as a control.
[1263] Rats were euthanized at lh, 4h, 8h and 24h post-injection, and femoral condyles were extracted for macroscopic and fluorescence evaluation using a Gel Logic Pro6000 Imaging System (530/600 filter) and Carestream software.
[1264] The results are shown in FIG. 9. These results demonstrate that compound 4 is present in the knee 24 hr after intra-articular injection ,
EXAMPLE B10. Staining of Small Intestine After Oral Administration of Compound 20
[1265] Six- to eight-week old C57BL/6 mice were anesthetized with 3% sevofluorane. A solution of 10 mg/ml Compound 4 in 20% cyciodextrin was administered by oral gavage at a dose of 100 mg/kg. A solution of 20% cyciodextrin was administered by oral gavage as a control . [1266] After 24h, mice were euthanized and a portion of small intestine and Peyer's patches were extracted, washed in PBS and fluorescence was measured using a Gel Logic Pro6000 Imaging System (530/600 filter) and Carestream software,
[1267] The results are shown in FIG. 10A and FIG. 10B. These results demonstrate that Compound 4 stains the small intestine but not Peyer's patches after oral administration.
EXAMPLE Bll. Organ Staining Following Oral Administration of Compound 4
[1268] Six- to eight-week old Sprague Dawley rats were anesthetized with 3% sevofluorane. A solution of 10 mg/ml Compound 4 or 10 mg/mi Safranin-0 (Sigma S8884) in 20% cyciodextrin (Sigma C4805) was administered by oral gavage at a dose of 100 mg/kg. A solution of 20% cyciodextrin was administered by oral gavage as a control.
[1269] After 24h, rats were euthanized and different organs were extracted and washed in PBS. Fluorescence was measured using a Gel Logic ProoOOO Imaging System (530/600 filter) and Carestream software to determine the localization of Compound 4 or safranin-O. The results are shown in FIG. 11A and FIG, 11B.
EX AMPLE B12. Organ Staining Following Intravenous Administration of Compound 4
[1270] Six- to eight-week old Sprague Dawley rats were anesthetized with 3% sevofluorane. A solution of 100 mg/ml Compound 4 in 100% DM SO was administered intravenously at a dose of 100 mg g. A solution of 100% DMSO was administered IV as a control.
[1271] After 2h, rats were euthanized and different organs were extracted and washed in PBS. Fluorescence was measured using a Gel Logic ProoOOO Imaging System (530/600 filter) and Carestream software to determine where Compound 4 was localized. The results are shown in FIG. 12A and FIG. 1.2B.

Claims

1. A method of preparing a pellet composition comprising a population of repair cells, comprising:
(a) incubating a population of repair cells with a compound under conditions sufficient for the compound to bind to the surface of the repair cells;
(b) subjecting the population to centrifugation to form a pellet; and
(c) culturing the pellet for less than three weeks,
wherein the compound is (i) a cationic dye multimer comprising a first cationic dye moiety, a second cationic dye moiety, and a first linker connecting the first and second cationic dye moieties; or (ii) a cationic dye comprising a linker.
2. The method of claim 1, wherein the cationic dye multimer further comprises a second linker and a third cationic dye moiety.
3. The method of claim 2, wherein the cationic dye multimer further comprises a third linker and a fourth cationic dye moiety.
4. The method of claim 1, wherein the first and second cationic dye moieties are different cationic dye moieties.
5. The method of claim 1, wherein the first and second cationic dye moieties are the same cationic dye moiety.
6. The method of any of claims 1-5, wherein each cationic dye moiety is independently selected from the group consisting of safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue.
7. The method of any of claims 1-6, wherein at least one cationic dye moiety is safranin- O and the pendant phenyl ring of the safranin-O optionally is substituted with 1-3 substituents independently selected from— NH2,— NHR,— NR2,—OH,— 0\ — NHCOCH3,— NHCOR, — OCH3,—OR,— C2H5,— R— C6H5,— NO2,— NR3 +, halo, trihalide,— CN, — SO3H,— COOH,— COOR,— CHO, and—COR, wherein R is C1-C6 linear or branched alkyl.
8. The method of claim 1, wherein the first cationic dye moiety is azure A and the second cationic dye multimer is safranin-O.
9. The method of any of claims 1-8, comprising a linker selected from the group consisting of:
Figure imgf000405_0001
(a) , in which n is 1-6, «/ is 1-4, and each * is an attachment site for a cationic dye moiety;
Figure imgf000405_0002
(a-1) , in which n is 1-6, nj is 1-4, and * is an attachment site for a cationic dye moiety;
Figure imgf000405_0003
(a 2) , in which n is 1-6, nj is 1-4, and * is an attachment site for a cationic dye moiety;
Figure imgf000405_0004
in which n is 0-6, nj is 1-4, and each * is an attachment site for a cationic dye moiety;
Figure imgf000405_0005
in which n is 0-6, wi is 1-4, and * is an attachment site for a cationic dye moiety;
Figure imgf000405_0006
, in which n is 0-6; «/ is 1-4; for each independent instance of Ra and Rb, (1) Ra and Rb independently are H or CH3, or (2) Ra and Rb are
'¾ ^ or '¾ *~ , or (3) two of CRaRb are '¾ ; and each * i is an attachment site for a cationic dye moiety;
Figure imgf000406_0001
, in which n is 0-6; is 1-4; for each independent instance of Ra and Rb, (1) Ra and Rb independently are H or CH3 or (2) Ra and Rb are '¾ ^
Figure imgf000406_0002
; and * is an attachment site for a cationic dye moiety;
Figure imgf000406_0003
, in which n is 0-6; tii is 1-4; for each independent instance of Ra and Rb, (1) Ra and Rb independently are H or CH3 or (2) Ra and Rb are '¾ ^ or
Figure imgf000406_0004
or (3) two of CRaRb are and * is an attachment site for a cationic dye moiety;
Figure imgf000406_0005
(d) , where k is 2-10; for each independent instance of Ra and Rb, Ra and Rb (1) independently are H or CH3, or (2) Ra and Rb are '¾ ^ or <*\ or (3) two of CRaRb are ; and each * is an attachment site for a cationic dye moiety;
Figure imgf000406_0006
(e) , in which n is 0-6, w is 1-4, and each * is an attachment site for a cationic dye moiety;
Figure imgf000406_0007
(e 1) , in which n is 0-6, rii is 1-4, and * is an attachment site for a cationic dye moiety;
Figure imgf000407_0001
, in which «? is 0-5, n2 is 1-5 and each * is an attachment site for a cationic dye moiety;
Figure imgf000407_0002
, in which ttj is 0-5, »2 is 1-5 and * is an attachment site for a cationic dye moiety;
Figure imgf000407_0003
, in which ni is 0-5, « is 1-5 and * is an attachment site for a cationic dye moiety;
Figure imgf000407_0004
(g) , in which ni is 0-5, «2 is 1-5 and each * is an attachment site for a cationic dye moiety;
Figure imgf000407_0005
(9-1 ) , in which ni is 0-5, W2 is 1-5 and * is an attachment site for a cationic dye moiety;
Figure imgf000407_0006
(g.2) , in which rtj is 0-5, n2 is 1-5 and * is an attachment site for a cationic dye moiety; , in which ni is 0-5, n2 is 1-5, and each * is an attachment site dye moiety;
Figure imgf000408_0001
(h- 1 ) , in which ni is 0-5, n2 is 1-5, and * is an attachment site for a cationic dye moiety;
Figure imgf000408_0002
(h-2) , in which n7 is 0-5, n2 is 1-5, and * is an attachment site for cationic dye moiety;
Figure imgf000408_0003
(') , in which tij and n2 independently are 1-5 and each * is an attachment site for a cationic dye moiety;
Figure imgf000408_0004
('· ) , in which tij and n2 independently are 1-5 and * is an attachment site for a cationic dye moiety;
Figure imgf000409_0001
(i.2) , in which »i and n2 independently are 1-5 and * is an attachment site for a cationic dye moiety;
Figure imgf000409_0002
, in which n2 is 1-5 and each * is an attachment site for a cationic dye moiety;
Figure imgf000409_0003
, in which n2 is 1-5 and * is an attachment site for a cationic dye moiety;
Figure imgf000409_0004
, in which n2 is 1-5 and * is an attachment site for a cationic dye moiety;
Figure imgf000410_0001
K , in which and l2 independently are 1-4, n is 1-4; ring
A is aryl, heteroaryl, cycloalkyl, or heterocyclyl, optionally substituted with halo or C1-C6 linear or branched alkyl; for each independent instance of Rai and Rbi, Rai and Rbi (1) inde endently are H or CH3, or (2) Rai and Rbi independently are '¾ * or
Figure imgf000410_0002
or (3) two of CRaiRbi are ν ¾· ; for each independent instance of Ra2 and Rb2, Ra2 and Rb2 (1) independently are
V7 0
H or CH3, or and Rb2 independently are " or '¾ or (3) two of
CRa2Rb2 are
Figure imgf000410_0003
and each * is an attachment site for a cationic dye moiety;
Figure imgf000410_0004
0 , in which li, l2, n, oi, and o2
independently are 1-4; ring A is aryl, heteroaryl, cycloalkyl, or heterocyclyl, optionally substituted with halo or C1-C6 linear or branched alkyl; for each independent instance of Rai and Rbi, Rai and Rbi (1) independently are H or
CH3, or (2) Rai and Rbi independently are '¾ ^ or '¾ or (3) two of
CRaiRbi are ; for each independent instance of Ra2 and Rb2, Ra2 and Rb2 (1) independently are H or CH3, or (2) Ra2 and Rb2 independently are
V7 0
'¾ ^ or '¾ or (3) two of CRa2Rb2 are '¾ ; for each independent instance of Ra and Rdi, Rci and Rdi (1) independently are H or CH3, or (2) Rdi independently are '¾ or '¾ or (3) two of CRciRdi are
Figure imgf000410_0005
; for each independent instance of R<.2 and Rj2, Rc2 and Rj2 (1) inde endently are H or CH3, or (2) Rc2 and Rd2 independently are or
Figure imgf000411_0001
; and each * is an attachment site for a cationic dye moiety;
Figure imgf000411_0002
1 ) , in which , h, n, oi, and o2 independently are 1-4; ring A is aryl, heteroaryl, cycloalkyl, or heterocyclyl, optionally substituted with halo or C1-C6 linear or branched alkyl; for each independent instance of Rai and Rbi, Rai and Rbi (1) independently are H or CH3, or (2)
Figure imgf000411_0003
Rai and Rbi independently are or (3) two of CRaiRbi are ¾· ¾ ; for each independent instance of R^ and Rb2, Ra2 and Rb2 (1) independently are H or CH3, or (2) Ra2 and Rb2 independently are '¾ ^ or O
'¾ or (3) two of CRa2Rb2 are "¾ ¾ ; for each independent instance of Rci and Rai, Rci and Rdi (1) independently are H or CH3, or (2) Rd and Rai independently are
Figure imgf000411_0004
or (3) two of CRciRai are ' «· ¾ ; for each independent instance of Rc2 and Ra2, Rc2 and Rj2 (1) independently a
H or CH3, or (2) Rc2 and Ra2 independently are '¾ ^ or '¾ or (3) two of '¾ and * is an attachment site for a cationic dye moiety;
Figure imgf000411_0005
(' 2) , in which //, l2, n, ø/, and o2 independently are 1-4; ring A is aryl, heteroaryl, cycloalkyl, or heterocyclyl, optionally substituted with halo or C1-C6 linear or branched alkyl; for each independent instance of Rai and Rbi, Rai and Rbi (1) independently are H or CH3, or (2)
Rai and Rbi independently are '¾ or " or (3) two of CRaiRbi are '¾ ¾ ; for each independent instance of R^ and Rb2, Ra2 and Rb2 (1) independently are H or CH3, or (2) Ra2 and R 2 independently are
Figure imgf000412_0001
or o
or (3) two of CRa2Rb2 are "*· for each independent instance of Rci and Rai, Rci and Rdi (1) independently are H or CH3, or (2) Rci and Rai independently are '¾ ^ or '¾ or (3) two of CRciRdi are x · for each independent instance of Rc2 and Rj2, Rc2 and Rj2 (1) independently are
H or CH3, or (2) R^ and Rd2 independently are '¾ or "Y ^ , or (3) two of * is an attachment site for a cationic dye moiety;
Figure imgf000412_0002
, in which n is 0-6, W/ is 1-4, and each
attachment site for a cationic dye moiety;
Figure imgf000412_0003
in which n is 0-6, η is 1-4, and * is an attachment dye moiety;
Figure imgf000412_0004
in which ri2 is 1-5 and each * is an attachment site for a cationic dye moiety;
Figure imgf000413_0001
{ ' , in which n2 is 1-5 and * is an attachment site for a cationic dye moiety;
in which n2 is 1-5 and * is an attachment site for a cationic
Figure imgf000413_0002
\°> , in which in which nj is 0-5, n2 is 1-5, n3 is 0-5, and * is an attachment site for a cationic dye moiety;
Figure imgf000413_0003
(P) , in which tij is 0-5, n2 is 1-5, n3 is 0-5, and * is an attachment site for a cationic dye moiety;
Figure imgf000414_0001
(^) , in which n.4 is 0-5, n2 is 1-5, and * is an attachment site for a cationic dye moiety;
Figure imgf000414_0002
> , in which W/ is 0-5, «2 is 1-5, «5 is 0-5, and * is an attachment site for a cationic dye moiety; and
Figure imgf000414_0003
, in which ni is 0-5, n2 is 1-5, n3 is 0-5 and * is an attachment site for a cationic dye moiety.
10. The method of claim 11, wherein the cationic dye multimer has a formula selected from the group consisting of:
Figure imgf000415_0001
formula (1): C ) , wherein each of Dl and
D2 is a cationic dye moiety, n is 1-6, and rtj is 1-4;
formula (2):
Figure imgf000415_0002
, wherein each of Dl and
D2 is a cationic dye moiety, n is 0-6, and rtj is 1-4;
Figure imgf000415_0003
formula (3): ^ , wherein each of Dl and D2 is a cationic dye moiety; n is 0-6, and «/ is 1-4; and, for each independent instance of Ra and Rb, (1) Ra and Rb independently are H or CH3, or (2)
Ra a
Figure imgf000415_0004
formula (4): (4) , wherein Dl and D2 each is a cationic dye moiety; k is 2-10; and, for each independent instance of Ra and Rb, (1) Ra and Rb independently are H or CH3, or (2) Ra and Rb are
¼- or ^ ,ΟΓ (3) two of CRaRb are ;
Figure imgf000416_0001
formula (4a): ^
wherein k is 2-10; for each independent instance of Ra and Rb, (1) Ra and
O
Rb independently are H or CH3, or (2) Ra and Rb are ¾ ^ or "¾ ^ or
(3) two of CRaRb are ; ¾, R2, R3, R4, Rs, and R independently are absent or independently are selected from— NH2,— NHR,— NR2, —OH,— O~,— NHCOCH3,— NHCOR,— OCH3,—OR,— C2H5, — R,— C6H5,— NO2,— NR3 +, halo, trihalide,— CN,— SO3H,— COOH, — COOR,— CHO, and—COR, wherein R is C1-C6 linear or branched alkyl;
Figure imgf000416_0002
formula (5): (5)
wherein each of Dl and D2 is a cationic dye moiety, n is 0-6, and rij is 1- 4;
Figure imgf000416_0003
formula (6): (6) , wherein each of Dl and
D2 is a cationic dye moiety, tii is 0-5, and «2 is 1-5;
Figure imgf000417_0001
formula (7): ; wherein each of Dl and
D2 is a cationic dye moiety, nj is 0-5, and n2 is 1-5;
formula (8):
Figure imgf000417_0002
, wherein each of Dl and D2 is a cationic dye moiety, «/ is 0-5, and «2 is 1-5;
Figure imgf000417_0003
formula (9): ^ , wherein each of Dl and D2 is a cationic dye moiety and nj and «2 independently are 1-5;
Figure imgf000417_0004
formula (10): (1 0) , wherein each of Dl and D2 is a cationic dye moiety and n is 1-6;
formula (10a):
Figure imgf000418_0001
wherein n is 1-6; Ri, R2, R3, R4, R5, and R6 independently are absent or independently are selected from— NH2,— NHR,— NR2,— OH,— O\ — NHCOCH3,— NHCOR,— OCH3,—OR,— C2H5,— R,— C6H5,— NO2, — NR3 +, halo, trihalide,— CN,— SO3H,— COOH,— COOR,— CHO, and — COR, wherein R is C1-C6 linear or branched alkyl;
Figure imgf000418_0002
formula (11): C ^ , wherein each of Dl and D2 is a cationic dye moiety; h and 12 independently are 1-4; n is 1-4; ring A is aryl, heteroaryl, cycloalkyl, or heterocyclyl, optionally substituted with halo or Cl- C6 linear or branched alkyl; for each independent instance of Ral and Rbi, Rai and Rbi (1) independently are H or CH3, or (2) Rai and Rbi are '¾ or O
'¾ <*\ or (3) two of CRaiRbi are '¾ ; and, for each independent instance of Ra2 and R 2, Ra2 and Rb2 (1) independently are H or CH3, or (2) Ra2 and
Rb2 are ¼ or
Figure imgf000418_0003
.;
Figure imgf000419_0001
formula (11a): (1 1 a)
wherein / and 12 independently are 1-4; n is 1-4; ring A is aryl, heteroaryl, cycloalkyl, or heterocyclyl, optionally substituted with halo or C1-C6 linear or branched alkyl; for each independent instance of Rai and Rbi, Rai and Rbi
(1) independently are H or CH3, or (2) Rai and Rbi are ' or '¾ * or (3) two of CRaiRbi are
Figure imgf000419_0002
; for each independent instance of Ra2 and Rb2,
Ra2 and Rb2 (1) independently are H or CH3, or (2) Ra2 and Rb2 are ' "^ or O
¼· or (3) two of CRa2Rb2 are
Figure imgf000419_0003
R2, R3, R4, R5, and R6
independently are absent or independently are selected from— NH2,— NHR, — NR2,—OH,— 0\— NHCOCH3,— NHCOR,— OCH3,—OR,— C2H5, — R,— C6H5,— NO2,— NR3 +, halo, trihalide,— CN,— SO3H,— COOH, — COOR,— CHO, and—COR, wherein R is C1-C6 linear or branched alkyl;
Figure imgf000419_0004
formula (12): C ^) , wherein each of Dl and D2 is a cationic dye moiety; , ¾, n, oi, and 02 independently are 1-4; ring A is aryl, heteroaryl, cycloalkyl, or heterocyclyl, optionally substituted with halo or C1-C6 linear or branched alkyl; for each independent instance of Rai and Rbi, Rai and Rbi (1) independently are H or CH3, or (2) and Rbi are or , or (3) two of CRaiRbi ; for each independent instance of Ra2 and Rb2, Ra2 and Rb2 (1) independently are H or CH3, or (2) Ra2 and Rb2 are ^ or '¾ ^ , or (3) two of CRa2Rb2 are
Figure imgf000420_0001
; for each independent instance of Rci and Rdi, Rd and Rdi (1) independently are H or CH3, or (2) Rd and Rdi independently are
Figure imgf000420_0002
or
O
v" , or (3) two of CRciRdi are "*· v ; for each independent instance of Rc2 and Rd2, Rc2 and Rd2 (1) independently are H or CH3, or (2) Rc2 and Rd2 independently
Figure imgf000420_0003
or (3) two of CRC2Rd2 are formula (12a):
Figure imgf000420_0004
(12a) wherein , l2, «, oj, and o2 independently are 1-4; ring A is aryl, heteroaryl, cycloalkyl, or heterocyclyl; for each independent instance of Rai and Rbi, Rai and Rbi (1) independently are H or CH3, or (2) Rai and R i are '¾ ^ or O
'¾ , or (3) two of CRaiRbi are "¾ ; for each independent instance of Ra2 and Rb2, Ra2 and Rb2 (1) independently are H or CH3, or (2) Ra2 and Rb2
are
Figure imgf000420_0005
or ' Ά¾ 5 or (3) two of CRa2Rb2 are wv ¾ ; for each independent instance of Rci and Rji, Rci and Rdi (1) independently are H or CH3, or (2)
Rci and Rdi independently are ^ or '¾ or (3) two of CRciRai are VV
¾ ; for each independent instance of Rc2 and Rd2, RC2 and Rj2 (1) independently are H or CH3, or (2) Rc2 and R,j2 independently are
Figure imgf000421_0001
or O
^ , or (3) two of CRc2Rd2 are ; Rt, R2, R3, ¾, Rs, and Re independently are absent or independently are selected from— NH2,— NHR, — NR2,—OH,— O ,— NHCOCH3,— NHCOR,— OCH3,—OR,— C2H5, — R— C6H5,— N02,— NR3 +, halo, trihalide,— CN,— SO3H,— COOH, — COOR,— CHO, and—COR, wherein R is C1-C6 linear or branched alkyl;
Figure imgf000421_0002
formula (12b): ' (1 2b) , in which each of Dl and D2 is a cationic dye moiety; Ιχ, l2, n, independently are 1-4; 07, and 02 independently are 1-8; ring A is aryl, heteroaryl, cycloalkyl, or heterocyclyl; for each independent instance of Rai and Rbi, Rai and Rbi (1)
V7 0
independently are H or CH3, or (2) Rai and Rbi are '¾ or '¾ <*\ or (3) two of CRaiRbi are ; for each independent instance of Ra2 and Rb2, Ra2 and Rb2 (1) independently are H or CH3, or (2) Ra2 and Rb2 are
Figure imgf000421_0003
or
Figure imgf000421_0004
, or (3) two of CRa2Rb2 are ; for each independent instance of
Rci and Rai, Rci and Rji (1) independently are H or CH3, or (2) Rci and Rji are
Figure imgf000422_0001
, n orr ( (3Ϊ) t twwno n off C C!RR-cIiRRdJiI a arree. ; for each independent instance of Rc2 and Rd2, Rc2 and Rd2 (1) independently are H or CH3, or (2)
Rc2 and Ra2 are ¼- ^ or ¼- or (3) two of CRc2Rd2 are ;
Figure imgf000422_0002
formula (13): , wherein each of Dl and D2 is a cationic dye moiety and n is 0-6, and itj is 1-4;
Figure imgf000422_0003
formula (14): (14)
in which each ofDl, D2, and D3 is a cationic dye moiety, n is 0-6, n is 1-4, nb is 0-6, and nbl is 0-6;
formula (15):
Figure imgf000422_0004
wherein each ofDl, D2, and D3 is a cationic dye moiety, n and nb
independently are 0-6, and nj and independently are 1-4;
Figure imgf000422_0005
formula (16): C ^) , wherein each ofDl, D2, and D3 is a cationic dye moiety; n and nb independently are 0-6; ni and nj independently are 1-4; for each independent instance of Rai and Rbi, ai and (1) independently are H or CH3, or (2) Rai and Rbi are or
Figure imgf000423_0001
; and, for each independent instance of Ra2 and Rb2, Ra2 and Rb2 (1) independently are H or CH3, or (2)
Ra2 and Rb2 are or <*\ or (3) two of CRa2Rb2 are ;
Figure imgf000423_0002
formula (17): (1 7)
wherein each of Dl, D2, and D3 is a cationic dye moiety; kj is 2-10; A¾ is 2- 10; for each independent instance of Rai and Rbi, Rai and Rbi (1) independently are H or CH3, or (2) Rai and Rbi are '¾ or '¾ or (3) two of CRaiRbi are
Figure imgf000423_0003
; and, for each independent instance of Ra2 and Rb2,
Ra2 and Rb2 (1) independently are H or CH3, or (2) Ra2 and R 2 are
Figure imgf000423_0004
or
Figure imgf000423_0005
, or (3) two of CRa2Rb2 are
Figure imgf000423_0006
formula (18): < 8>
wherein each of Dl, D2, and D3 is a cationic dye moiety, n and nb
independently are 0-6, and nj and % independently are 1-4; formula (19):
Figure imgf000424_0001
wherein each of Dl, D2, and D3 is a cationic dye moiety, tii and nw independently are 0-5, and n2 and /¾2 independently are 1-5;
formula (20):
Figure imgf000424_0002
(20)
wherein each of Dl and D2 is a cationic dye moiety, rij and ½ independently are 0-5 and n2 and nb2 independently are 1-5;
Figure imgf000424_0003
Figure imgf000424_0004
formula (21): (^1 ) , wherein each of
Dl, D2, and D3 is a cationic dye moiety, tij and independently are 0-5 and «2 and nb2 independently are 1-5;
Figure imgf000425_0001
formula (22): (22) ^ wherein each of
Dl, D2, and D3 is a cationic dye moiety, «/, «2, w//, and nbi independently are 1-5;
formula (23):
Figure imgf000425_0002
wherein each of Dl, D2, and D3 is a cationic dye moiety and n and nb independently are 1-6;
Figure imgf000425_0003
formula (24): , wherein m is 2; each of Dl, a first D2, and a second D2 is a cationic dye moiety; lj and l2 independently are 1-4; ring A is aryl, heteroaryl, cycloalkyl, or heterocyclyl, optionally substituted with halo or C1-C6 linear or branched alkyl; for each independent instance of Rai and R^, Rai and Rbi (1) independently are H or CH3, or (2)
Figure imgf000425_0004
each independent instance of Ra2 and Rb2, Ra2 and Rb2 (1) independently are CH3, or (2) Ra2 and Rb2 are \ or (3) two of CRa2Rb2 are
formula (24a):
Figure imgf000426_0001
(24a) wherein m is 2; // and l2 independently are 1-4; ring A is aryl, heteroaryl, cycloalkyl, or heterocyclyl, optionally substituted with halo or C1-C6 linear or branched alkyl; for each independent instance of Ral and Rbi, Rai and Rbi
(1) independently are H or CH3, or (2) Rai and Rbi are "x ^ or '¾ <*\ or (3) two of CRaiRbi are ^ ^i for each independent instance of Ra2 and Rb2,
Ra2 and Rb2 (1) independently are H or CH3, or (2) Ra2 and Rb2 are
Figure imgf000426_0002
or O
^ , or (3) two of CRa2Rb2 are - ^¾ ; 1S R2, R3, R4, R5, and R6 independently are absent or independently are selected from— NH2,— NHR, — NR2,—OH,— 0\— NHCOCH3,— NHCOR,— OCH3,—OR,— C2H5, — R,— C6H5,— NO2,— NR3 +, halo, trihalide,— CN,— SO3H,— COOH, — COOR,— CHO, and—COR; and R is C1-C6 linear or branched alkyl;
Figure imgf000427_0001
formula (25): (25)
wherein m is 2; each of Dl, a first D2, and a second D2 is a cationic dye moiety; lj, l2, n, Oi, and o2 independently are 1-4; ring A is aryl, heteroaryl, cycloalkyl, or heterocyclyl, optionally substituted with halo or C1-C6 linear or branched alkyl; for each independent instance of Rai and Rbi, Rai and Rbi
(1) independently are H or CH3, or (2) Ral and Rbi are ^ or '¾ <*\ or (3) two of CRalRbi are ; for each independent instance of Ra2 and Rb2,
Ra2 and Rb2 (1) independently are H or CH3, or (2) Ra2 and Rb2 are
Figure imgf000427_0002
or
O
'¾ , or (3) two of CRa2Rb2 are V <1 ; for each independent instance of Rci and Rdi, R^ and RJI (1) independently are H or CH3, or (2) Rd and Rai independently are '¾ ^ or "¾ or (3) two of CRciRdi are ^ ; for each independent instance of Rc2 and Ra2, Rc2 and Rd2 (1) independently are
H or CH3, or (2) Rc2 and Rd2 independently are
Figure imgf000427_0003
or (3) two of
Figure imgf000427_0004
formula (25a):
Figure imgf000428_0001
(25a)
, wherein m is 2; Zi, Z2, n, οχ, and o2 independently are 1-4; ring A is aryl, heteroaryl, cycloalkyl, or heterocyclyl, optionally substituted with halo or Cl- C6 linear or branched alkyl; for each independent instance of Rai and Rbi, Rai and Rbi (1) independently are H or CH3, or (2) Rai and Rbi are
Figure imgf000428_0002
or
O
'¾ r~ , or (3) two of CRaiRbi are
Figure imgf000428_0003
for each independent instance of Ra2 and Rb2, a2 and Rb2 (1) independently are H or CH3, or (2) Ra2 and Rb2 are
Figure imgf000428_0004
t twwno n off C CRRa-I2RRLb2I a arme ¾ ; for each independent instance of Rci and Rai, Rci and Rai (1) independently are H or CH3, or (2)
Rci and Rai independently are
Figure imgf000428_0005
or (3) two of CRciR<ii are
; for each independent instance of R^ and Rj2, Rc2 and Rj2 (1) independently are H or CH3, or (2) Rc2 and Rj2 independently are
Figure imgf000428_0006
or O
or (3) two of CRc2Rd2 are ^ ^ - R2, R3, R5, and Re independently are absent or independently are selected from— NH2,— NHR, — NR2,—OH,— 0\— NHCOCH3,— NHCOR,— OCH3,—OR,— C2H5,— R,— C6H5,— NO2,— NR3 +, halo, trihalide,— CN,— SO3H,— COOH,— COOR,— CHO, and—COR; and R is C1-C6 linear or branched alkyl;
Figure imgf000429_0001
formula (26), (27), (28), (29), (30), (31), or (32): (26)
Figure imgf000429_0002
(27) (28) (29)
Figure imgf000429_0003
, wherein D is a cationic dye moiety, nx is 0-5, ny is 1-5, and L is absent or L is a linker selected from linker (a.l), linker (a.2), linker (b.l), linker (c.l), linker (c.2), linker (d), linker (e.l), linker (f.l), linker (f.2), linker (g.l), linker (g.2), linker (h.l), linker (h.2), linker (i.l), linker (i.2), linker (j.l), linker (j.2), linker (k), linker (1.1), linker (1.2), is linker (m.l), linker (n.l), linker (n.2), linker (o), linker (p), linker (q), linker (r), and linker (s);
Figure imgf000430_0001
formula (33): (33) , wherein each of Dl, D2, D3, and D4 is a cationic dye moiety and L is absent or L is a linker selected from linker (a.l), linker (a.2), linker (b.l), linker (c.l), linker (c.2), linker (d), linker (e.l), linker (f.l), linker (f.2), linker (g.l), linker (g.2), linker (h.l), linker (h.2), linker (i.l), linker (i.2), linker (j.l), linker (j.2), linker (k), linker (1.1), linker (1.2), is linker (m.l), linker (n.l), linker (n.2), linker (o), linker (p), linker (q), linker (r), and linker (s); and
Figure imgf000431_0001
formula (34): (34) , wherein each of
Dl, D2, and D3 is a cationic dye moiety and L is absent or L is a linker selected from linker (a.l), linker (a.2), linker (b.l), linker (c.l), linker (c.2), linker (d), linker (e.l), linker (f.l), linker (f.2), linker (g.l), linker (g.2), linker (h.l), linker (h.2), linker (i.l), linker (i.2), linker (j.l), linker (j-2), linker (k), linker (1.1), linker (1.2), is linker (m.l), linker (n.l), linker (n.2), linker (o), linker (p), linker (q), linker (r), and linker (s); or
wherein the cationic dye multimer is
Figure imgf000431_0002
11. The method of any of claims 1-10, wherein the cationic dye is selected from the group consisting of safranin-O, toluidine blue, azure A, azure B, azure C, acridine orange, acriflavine, and methylene blue.
12. A pellet composition formed by the method of any of claims 1-11.
13. A pellet composition comprising a compound and one or more repair cells, wherein the compound is a cationic dye multimer as recited in any of claims 1-11.
14. A pharmaceutical composition comprising the pellet composition of claim 12 or claim 13.
15. A method of repairing a tissue injury in an individual, comprising administering to an injured tissue:
(a) the pellet composition of claim 12 or claim 13; or
(b) the pharmaceutical composition of claim 14.
16. The method of claim 15, wherein the pellet composition of claim 14 is administered, wherein the pellet composition is not cultured before the step of administering.
17. The method of claim 15 or claim 16, wherein the injured tissue is selected from cartilage, pancreas, kidney, intestine, and heart.
18. The method of any of claims 1-11, the pellet composition of claim 12 or claim 13, or the pharmaceutical composition of claim 14, wherein the repair cells are mesenchymal stem cells (MSCs).
19. The method or the pellet composition or the pharmaceutical composition of claim 18, wherein the MSCs are autologous MSCs.
20. Use of the pellet composition of claim 12 or claim 13 or the pharmaceutical composition of claim 14 for repairing a tissue injury in an individual.
PCT/US2016/044395 2015-07-29 2016-07-28 Compositions containing repair cells and cationic dyes WO2017019833A1 (en)

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