AU8379498A - Indium photosensitizers for pdt - Google Patents

Description

WO 00/00204 PCT/US98/13601 INDIUM PHOTOSENSITIZERS FOR PDT. BACKGROUND OF THE INVENTION Porphyrins and related pyrrolic macrocycles, particularly tetrapyrrolic macrocycles, as well as many other light absorbing compounds are currently receiving a 5 great deal of attention with regard to photosensitized medicine, especially in the field of Photodynamic therapy (PDT) t . The therapy necessarily involves the localization of a photosensitizing agent at or near a site of disease. The sensitizer, upon illumination in the presence of oxygen, produces cytotoxic species of oxygen such as singlet oxygen or oxygen radicals, which destroy the diseased cells. As the sensitizer is innocuous at the o10 therapeutic dose, and only becomes active on illumination with light of a specific wavelength, PDT offers the possibility of a level of control or selectivity in the treatment of diseases not found with other current methods (e.g. conventional chemotherapy). Photodynamic therapy has wide application to modern medicine, targeting diseases such as cancers, cardiovascular restenosis and plaques, psoriasis, viral infections, benign 15 prostate hyperplasia and diabetic retinopathy. In addition, photodynamic therapy may also be useful for the sterilization of blood, an area of increasing concern, especially now with the advent of AIDS and the transmission of HIV through blood transfusions. Most research on PDT has centered on a complex mixture consisting of ill-defined porphyrin dimers, trimers and oligomers 2 , which is marketed under the designation 20 Photofrin II®. This complex mixture has recently been recommended for approval in the treatment of obstructed endobronchial tumors by the Food and Drug Administration Advisory Panel. Although the mixture has demonstrated the potential benefits of PDT, it has by virtue of its composition a number of associated disadvantages. For example, each of its components has varied subcellular localizations, depending on structure and inherent 25 differences in photophysical properties. This makes the interpretation of pharmacokinetic data difficult. In addition, the composition of the oligomers is often difficult to reproduce and changes, depending on the conditions under which a solution 3 thereof is stored. Hence, the true "active components" may vary considerably. The mixture has a less than optimal light absorption profile (630nm, E-3,000cm'M'). Numerous studies on light 30 penetration through tissues show that longer wavelength light penetrates deeper into tissues 4 . While not all applications of PDT require deep penetration of light, many applications of PDT require the maximum depth of light penetration possible (for example the treatment of brain tumors). The mixture has a severe adverse normal skin response to WO 00/00204 PCT/US98/13601 2 light, which often lasts for up to 12 weeks 5 after therapy. During this time patients must avoid strong light, as otherwise severe burns and edema occur. Several well characterized second generation sensitizers (SnET2 6 , ZnPc 7 ,

BPDMA

8 , THPC 9 ) are currently in phase I/II clinical trials and the continued development 5 of new sensitizers that show improved therapeutic efficacy is crucial to the future progress of the therapy. The development of new photosensitizers that possess all the basic requirements to be effective PDT drugs is not an easy task. While the optimal photophysical properties of a second generation drug are well defined, the factors which aid in the localization of photosensitizers to tissues are not. Several investigators have 10 attempted to ascertain structure-activity relationships in ring systems that lend themselves to chemical modification without dramatically influencing the photophysical properties of the compounds. Woodburn and coworkers, working on hematoporphyrin based analogues, have proposed that anionic compounds tend to localize in lysosomes, while cationic photosensitizers tend to localize in the mitochondria. Pandey and coworkers have 15 suggested that the lipophilicity of the compound is important, and have demonstrated in a chlorophyll derived series that PDT effects vary with the length of the ether carbon chain. Unfortunately, many of the correlation's found in one group of photosensitizing compounds do not transfer to different groups of photosensitizing compounds. Thus, while structure-activity relationships are valuable for a particular class of compound whose 20 geometry and spatial arrangements vary only slightly, a different class of compound, that inherently has its own spatial and geometric parameters, must have its own structure activity relationships investigated. This in itself is a large time consuming process with ultimately no guarantees of enhanced localization or improved PDT efficacy for the modified compound. 25 The instant invention is based upon the discovery of a single simple chemical modification of compounds having a pyrrolic core involving the coordination of a non radioactive indium salt into the central cavity of the pyrrolic core to produce an indium pyrrolic complex, which markedly enhances the biological efficacy of compounds as photosensitizers for PDT. 30 Two isotopes of indium occur naturally: In' 1 3 and In' 15; the former (natural abundance 4.23%) has no radioactivity, while the latter (natural abundance 95.77%) has a half life of 6 x 1014 years, and, as a result, is also considered to be non-radioactive. Other WO 00/00204 PCT/US98/13601 3 indium nuclides have half lives ranging from 50.0 days (for In I14m) to 0.2 second (for In 109m) THE PRIOR ART Tetrapyrroles containing Indium 1'' (half life 2.81 days) and other metals are 5 known in the art, being disclosed, by way of example, in Japanese Kokai 3-261786, 1991, Mauclaire et al., US patent No. 5, 268,371 and in Maier et al., US patent No. 5,674,467, which also disclose their use for diagnostic imaging. The metal-tetrapyrrole compounds are all water soluble, and contain functional groups capable of coupling a biologically active molecule, such as an antibody, to the tetrapyrrolic nucleus. The compounds usually 10 are prepared by reacting a porphyrin derivative with a solution of a salt of the metal to be complexed at a temperature and for a time sufficient to obtain the metal tetrpyrrole compound. For example, when a metal salt of indium 1' is heated for three hours at 110 0 C. in a porphyrin solution to which a mixture of acetic acid and sodium acetate has been added, an In lporphyrin is produced. Although the preparation of such 15 metalloporphyrins is known and the compounds have been discussed in the context of radiocontrasting agents, surprisingly, so far as is known, there has been no report on the efficacy of indiumporphyrins as therapeutic photosensitizers. In view of the substantial prior art involving indium tetrapyrroles, it is indeed surprising to discover that complexes of non-radioactive indium with tetrapyrroles exhibit a marked improvement in their 20 cytocidal effect in vivo when compared with other metallotetrapyrrole complexes. Sakata, US patent No. 4,849,207, discloses compounds having the following structure: R3 R12 R4 2R5 Z R1 In R 10 R R6 R9 R8 R7 WO 00/00204 PCT/US98/13601 4 where: RI, R2, R4 and R6 are methyl, R8, R10, R 11 and R12 are H, and R7 and R9 are 5 CH 2

CH

2 COR 13 (where R13 is a residue which results when H is removed from an amino acid), R3 and R5 are ethyl, and In is not radioactive, i.e., is In ' 3 or In 15 Japanese Kokai 5-97857 discloses compounds having the following structure Where R is CH(OR)Me, R is alkyl, R2 is a residue derived by removing H from an 10 amino acid, and M is 2H, Ga, Zn, Pd, In or Sn M RI M N1' N M Me O2R2 CO2R2 Where R1I is CH(OR)Me, R is alkyl, R2 is a residue derived by removing H from an 10 amino acid, and M is 2H, Ga, Zn, Pd, In or Sn The following references are cited above: 1. For an overview of photodynamic therapy see"Photodynamic Therapy of Neoplastic Disease", Vol. I and II. Ed. Kessel, D., CRC Press, 1990. 2 ."Photodynamic Therapy of Neoplastic Disease", Vol. I and II. Ed. Kessel, D., CRC Press, 1990 p1-1 2 . 3. Byrne, CJ, Ward, A.D., Marshallsay, C.J. Photochem. Photobiol., 46, 575, 1987. 4. a)Svaasand, L.O. Ellingsen. R. Photochem. Photobiol. 41, 73, 1985:b) Bolin, F.P., Preuss, L.E., Cain, B.W., in "Porphyrin Localization and Treatment of Tumours". Eds. Doiron, D.R., Gomer., C.J. Alan Liss, New York, 211, 1984. 5. Razumn, N., Balchum, O.J., Profio, A.E., Carstens, C. Photochem Photobiol. 46, 925, 1987. 6. Kessel, D., Morgan, A.R., Garbo, G.M., Photochem. Photobiol., 54(2), 193, 1991. 7. Ginevra, F., Biffanti, S., Pagnan, A., Biolo, R., Reddi, E., Jori, G., Cancer Letters, 49, 59, 1990. 8. Aveline, B., Hasan, T., Redmond, R.W., Photochem. Photobiol. , 59(3), 328, 1994. 9. Bonnett, R., White, R.D., Winfield, U., Berenbaum, M.C., Biochen. J., 261, 277, 1989.

WO 00/00204 PCT/US98/13601 5 SUMMARY OF THE INVENTION It is an object of the present invention to provide pyrrolic compounds that absorb light at long wavelengths for use in photodynamic therapy and diagnosis of disease states. It is another object to provide a reaction product of (A) P where P is a pyrrolic 5 derivative and (B) In " 3

X

3 and/or In" 5

X

3 (where X is a charge balancing ion, either organic or inorganic) such as to provide the reaction product (C) PIn' n 3 ,Xn and/orPIn 1 5 nXn, where indium is coordinated to the pyrrolic derivative and n = 1, 2, 3. It is yet another object of the invention to provide a reaction product of (C) PIn' 1 3 nX n and/or PIn' 1 5 nXn with a neucleophile Y, such that a reaction product (D) 10 PIn" 3 YnXz and/or PIn1 nYnXz is obtained (where Y is a charge balancing ion, either organic or inorganic n= 1, 2

,

3 and z = 0, 1, 2, 3). It is still another object to provide compounds PIn" 3X and/or Pin' 1 5 X that may be used to treat diseases such as atherosclerosis, restenosis, cancer, cancer pre-cursors, non cancerous hyperproliferating diseases, psoriasis, macular degeneration, glaucoma and 15 viruses, benign prostate hyperplasia, rheumatoid arthritis and to aid in the diagnosis of these disease states. DESCRIPTION OF THE PERFERRED EMBODIMENTS 20 The present invention provides derivatives of photoactivatable compounds, some of which are shown in the following Examples, in table 1, and in Figs. 1- 5 via the introduction of non-radioactive indium into the macrocycle. The resulting products can be used to diagnose and treat disease states. Additionally, the ligand on the indium complex may then be further chemically or biochemically modified ex-vivo or in-vivo to form a 25 different pyrrolic indium complex which is capable of binding to important blood plasma components or cell transport proteins that enhance sensitizer uptake at the diseased tissue site. Additional functionality around the pyrrolic structure can be used to attach biomolecules, examples of which may be antibodies, growth hormones and growth factors 30 or other disease specific molecules, or to aid such factors as water solubility, lipophilicity or hydrophobicity which are known factors that influence drug uptake in tumor disease tissue.

WO 00/00204 6 PCT/US98/13601 The following Examples are presented solely for the purpose of disclosing and illustrating the invention, and are not to be construed as limiting. In all of the procedures described in the examples, indium, where used, was the natural material, a mixture of abouit 4.23% In"3 and 95.77% In 11 5 . The following abbreviations are used in the 5 examples: mL means millilter or milliliters, g means gram or grams; mg means milligram or milligrams; pg means microgram or micrograms Example 1, Preparation of Indium Methyl pyropheophorbide from methyl pyropheophorbide: HC= CH 2 N N N ,,,N 'H H2 0 H2

CH

3 02C M is 2H in methyl pyropheophorbide, and a mixture of In 1 3 Cl and In 15 Cl in Indium methyl pyropheophorbide 10 10 Methyl pyropheophorbide (0.5g) was dissolved in acetic acid (100mL); Indium chloride (0.5g) and anhydrous sodium acetate (0.5 g) were added, and the solution was refluxed for 3 hrs. The solution was taken to dryness by rotary evaporation and the solid residue dissolved in dichloromethane / water (100mL/ 100lmL). The organic layer was 15 washed several times with 0.5 N HC1/water (200mL), collected and dried over anhydrous sodium sulfate (20g). The organic layer was filtered and evaporated to dryness. The resulting residue was crystallized from methanol / dichloromethane. Yield 0.45g.

WO 00/00204 7 PCT/US98/13601 Example 2, preparation of Indium tert-butyl phthalocyanine: R3 R4 R4 R3 R2

-

R2 RRI M N N RI 1RI R2 R2 R3 R4 R4 R3 R3 one of R2 and R3 is tert-butyl while the other and RI and R4 are H; and M is In 3 Cl, In 115 Cl or a mixture of Int 113 CI and In 115 Cl 4-tert-butyl-1,2-dicyanobenzene (2g) and Indium chloride (2.0g) were mixed thoroughly in a round bottom flask with stirring. The mixture was heated at 160 0 C for 2 5 hrs and the reaction vessel cooled to room temperature. The crude phthalocyanine was extracted from the resulting green solid using hot dichloroethane and the green solution evaporated by rotary evaporation. The resulting solid was dissolved in 7% acetone / dichloromethane and chromatographed on silica using 7% acetone / dichloromethane as eluent. The major green fraction was collected and recrystallized from methanol/ 10 dichloromethane. Yield, 1.1g.

WO 00/00204 8 PCT/US98/13601 Example 3, Preparation of Indium Benzoporphyrin derivative from Benzoporphyrin derivative dimethyl ester. HC= CH2 M N N N N

COMM

e COMe Where M is In 1 13 Cl, In 5 C1, or a mixture of Inm 3 CI and In 115 CI in indium benzoporphyrin derivative dimethyl ester and 2H in Ring B isomer benzopor phyrin derivative dimethyl ester Ring B isomer, Benzoporphyrin derivative dimethyl ester (100mg) was dissolved 5 in acetic acid (50mL) and Indium chloride (0.2g) and anhydrous sodium acetate (0.2 g) were added; the solution was refluxed for 3 hrs. The solution was taken to dryness by rotary evaporation and the solid residue dissolved in dichloromethane / water (100mL/ 100mL). The organic layer was washed several times with 0.5 N HCl/water (200mL), collected and dried over anhydrous sodium sulfate (20g). The organic layer was filtered 10 and evaporated to dryness. The resulting residue was chromatographed on silica using 5% MeOH / dichloromethane as eluent and the major green fraction collected. The solvent was removed by rotary evaporation and the solid crystallized from hexane / dichloromethane. Yield 50mg. 15 WO 00/00204 9 PCT/US98/13601 Example 4, Preparation of Indium m-hydroxy tetraphenylchlorin:from Tetrakis (3 hydroxyphenyl)chlorin R1 R5 R2 R4 R3 R2 R 3 O e N- R3 R2 Hyroenisamitro I n" Gln I 1 nd N Z is RI lae RI

NN

' R5 R4 4 R5 R4 R3 R5 R2 R1 5 Where each R2 is OH, each R I, R3, R4 and R5 is Hydrogen, In is a mixture of In[13 Cl and In 115 C1, and Z is C1 10 Tetrakis (3-hydroxyphenyl)chlorin (100mg) was dissolved in acetic acid and the solution purged with argon. Indium chloride (0.2g) and anhydrous sodium acetate (0.2 g) was added and the solution refluxed for 3 hrs under argon. The solution was taken to dryness by rotary evaporation and the solid residue dissolved in dichloromethane / water (100mL/ 100mL). The organic layer was washed several times with 0.5 N HCl/water 15 (200mL), collected and dried over anhydrous sodium sulfate (20g). The organic layer was filtered and evaporated to dryness. The resulting residue was chromatographed on silica using 5% MeOH / dichloromethane as eluent and the major green fraction collected. The solvent was removed by rotary evaporation and the solid crystallized from hexane / dichloromethane. Yield 60mg. 20 WO 00/00204 10 PCT/US98/13601 Example 5, preparation of In Octaethylbenzochlorin (9) from Octaethylbenzochlorin ("OEBC") R4 5 // R3- R6 N' N R2 N N 1 / R7 k8 Each of RI through R8 is ethyl. In Octaethyl benzochlorin, M is 2H, and in Indium octaethyl benzochlorin M is In"' Z, In' 15 Z or a mixture of In 1 Z and In1 1 5 Z Z is Cl Octaethylbenzochlorin (100mg) was dissolved in acetic acid and Indium chloride 5 (0.2g) and anhydrous sodium acetate (0.2g) were added. The solution was refluxed for 3 hrs under argon. The solution was taken to dryness by rotary evaporation and the solid residue dissolved in dichloromethane (lOmL). The resulting solution was chromatographed on silica using 5% MeOH / dichloromethane as eluent and the major green fraction collected. The solvent was removed by rotary evaporation and the solid io crystallized from hexane / dichloromethane. Yield 110mg.

WO 00/00204 11 PCT/US98/13601 Example 6, preparation of InOEBCSO 2 NH(CH2)30H (10) from OEBCSO 2

NH(CH

2 )30H R4 5 R. R6 N' N R2 1 ~R7 R Each of RI through R8 is ethyl 5 In Octaethyl benzochlorin, M Is 2H, and in Indium Octaethyl benzochlorin M is a mixture of In" 3 Cl and In' 15 Cl R is SO 2

NH(CH

2

)

3 0H 10

OEBCSO

2 NH(CH2)30H (100mg) was dissolved in dimethylformamide (DMF) (25mL) and InCl3 (100mg) was added. The solution was refluxed for 6 hrs and the DMF was removed by rotary evaporation. The residue was dissolved in dichloromethane (10mL) and the resulting solution was chromatographed on silica using 5% MeOH / 15 dichloromethane as eluent. A minor fore running green band was collected and discarded and the more polar major green fraction was collected. The solvent was removed by rotary evaporation and the solid crystallized from hexane / dichloromethane. Yield 52mg.

WO 00/00204 PCT/US98/13601 12 InOBCO , .CH.2CH20CH2CHO OCHgCH20CH2CH20CH3 (17) Example 7, Preparation of InOEBCSO2 CHCH20CH2CH CH CH20CHCH20CH (17) CH2CHOCH2CH,,OCH2CH2OCH2CH2OCH3 -- CH 2

CH

2

OCH

2

CH

2 O0CH 2

CH

2

OCH

2

CH

2 OCH3 fromEBCO2NCH2)CH20CH2CH20CHz)CH20CH2CH20OCH3 R4 5 R. R6 N N / / R2 N\ N PR2N 8 Where each of R1 through R8 is ethyl M is In 113 Z, In 115 Z, or a mixture of In l 3 Z and In l 5 Z in In Octaethyl benzochlorin and 2H in Octaethyl benzochlorin RiSo -H,CH,OCH,CHOCH,CH,OCH,CH,OCH3 R is SONHCHOCHCH20CHOCHOCHOCHOCH Z is Cl

OEBCSO

2

N--CHCH

2 0CH2CH20CH2CH20CHCHOCH3 (400 mg) was

CH

2

CH

2

OCH

2

CH

2

OCH

2

CH

2

OCH

2 CH2OCH3 dissolved in acetic acid (150mL) and Indium chloride (0.4g) and anhydrous sodium 5 acetate (0.3g) were added. The solution was refluxed for 3 hrs under argon. The solution was taken to dryness by rotary evaporation and the solid residue dissolved in dichloromethane (10mL). The resulting solution was chromatographed on silica using 5% acetone / dichloromethane as eluent and the major green fraction collected. The solvent was removed by rotary evaporation and the solid crystallized from hexane / 10 dichloromethane. Yield 420mg.

WO 00/00204 13 PCT/US98/13601 Example 8, Preparation of InOEBCSO 2

NHC(CH

2 OH)3 (19) from OEBC

SO

2

NHC(CH

2

OH)

3 4 5 R. R6 R2 N' N . / R7 8 R Each of RI through R8 is ethyl In Octaethyl benzochlorin, M 5 Is 2H, and in Indium Octaethyl benzochlorin M is a mixture of In"' 13 Cl And In 15 Cl R is SO 2

NHC(CH

2

OH)

3 10 OEBCSO 2

NHC(CH

2 OH)3 (100mg) was dissolved in bromobenzene (50mL) and Indium chloride (0.2g) and anhydrous sodium acetate (0.2g) were added. The solution was refluxed for 5 hrs under argon. The solution was taken to dryness by rotary evaporation and the solid residue dissolved in dichloromethane (10mL). The resulting solution was chromatographed on silica using 5% acetone / dichloromethane as eluent and the major 15 green fraction collected. The solvent was removed by rotary evaporation and the solid crystallized from hexane / dichloromethane. Yield 105mg.

WO 00/00204 14 PCT/US98/13601 Example 9, preparation of InOEBCSO 2 NH (CH 2

)

4

CH(NH

2

)CO

2 H (21) from

OEBCSO

2 NH (CH 2

)

4 CH(NH2)CO 2 H R4p Each of R1 through R8 is ethyl In Octaethyl benzochlorin, M Is 2H, and in Indium Octaethyl Benzochlorin M is a mixture of In 113 Cl and Inl15 Cl 10 R is SO2NH (CH2)4CH(NH2)CO2H OEBCSO2NH (CH2)4CH(NH2)CO2H (100mg) was dissolved in acetic acid and R2 N' N ~ /R7 8 Indium chloride (0.2g) and anhydrous sodium acetate (0.2g) were added. The solutionethyl In Octaethyl benzochlorin. M Isrefluxed for 3 hours under argon. The solution Indiumwas taken to dryness by rotary evaporation Benzochlorin M is a mixture of In 113 CI and InIl15 CI 10 R is S0 2 NH (CH 2

)

4 CH(NH2)COH OEBCS0 2 NH (CH 2

)

4

CH(NH

2

)CO

2 H (100mg) was dissolved in acetic acid and Indium chloride (0.2g) and anhydrous sodium acetate (0.2g) were added. The solution refluxed for 3 hours under argon. The solution was taken to dryness by rotary evaporation 15 and the solid residue dissolved in dichloromethane (10mL). The resulting solution was chromatographed on silica using 5% MeOH / dichloromethane as eluent and the major green fraction collected. The solvent was removed by rotary evaporation and the solid crystallized from hexane / dichloromethane. Yield 110mg. 20 WO 00/00204 PCT/US98/13601 15 Example 10, Preparation of Indium 2-desvinyl-2-acetyl pyropheophorbide (26) from 2-desvinyl-2-acetyl pyropheophorbide (26) O = C - CH 3 N N N' N / H H2 0 H2

CH

3 02C M is 2H in 2-desvinyl-2-acetyl 5 Pyropheophorbide and a mixture of In" 3 CI and In i t5 CI in Indium-2-desvinyl-2-acetyl pyropheophorbide 10 2-Desvinyl-2-acetyl pyrropheophorbide (100mg) was dissolved in acetic acid and Indium chloride (0.2g) and anhydrous sodium acetate (0.2g) were added. The solution was refluxed for 3 hrs under argon. The solution was taken to dryness by rotary evaporation and the solid residue dissolved in dichloromethane (10mL). The resulting solution was chromatographed on silica using 5% acetone / dichloromethane as eluent and the major 15 green fraction collected. The solvent was removed by rotary evaporation and the solid crystallized from hexane / dichloromethane. Yield 100mg.

WO 00/00204 PCT/US98/13601 16 Example 11, Preparation of Indium 2-desvinyl-2-formyl pyropheophorbide (27) from 2-desvinyl-2-formyl pyropheophorbide O=CH N N H H' 0 H2

CH

3 02C 5 M is 2H in 2-desvinyl-2-formyl Pyropheophorbide and a mixture of In" 3 CI and In" 5 Cl in Indium-2-desvinyl-2-formyl pyropheophorbide 10 2-Desvinyl-2-formyl pyropheophorbide (100mg) was dissolved in acetic acid (20mL) and Indium chloride (100mg) was added. Diisopropylethylamine (0.3ml) was added and the solution refluxed until no more starting material remained by TLC (5%acetone / dichloromethane). The acetic acid was removed by rotary evaporation and the residue 15 dissolved in dichloromethane and washed with 10% NH 4 Cl (2 x 50mL). The organic phase was separated, dried over sodium sulfate filtered and rotoevaporated to dryness. The residue was dissolved in dichloromethane and purified by chromatography on silica using 5% acetone / dichloromethane as eluent followed by 20% acetone / dichloromethane as eluent. A less polar green fraction was collected and recrystallized from dichloromethane / 20 hexane. A second more polar green fraction was collected and discarded. Yield of (27) = 62mg.

WO 00/00204 17 PCT/US98/13601 Example 12, preparation of Indium Chlorin e6 trimethyl ester (28) from Chlorin e6 trimethyl ester H / / H N'

COCH

3

CHCOCH

3

COCH

3 M is 2H in Chlorin e6 5 Trimethyl eater and a mixture of In" 3 Cl and In" 5 Cl in Indium-Chlorin e6 trimethyl ester Chlorin e6 trimethyl ester (150mg) was dissolved in acetic acid (20mL) and 10 Indium chloride (150mg) added. Diisopropylethylamine (0.3ml) was added and the solution refluxed until no more starting material remained by TLC (5%acetone / dichloromethane). The acetic acid was removed by rotary evaporation and the residue dissolved in dichloromethane and washed with 10% NH 4 Cl (2 x 50mL). The organic phase was separated, dried over sodium sulfate, filtered and rotoevaporated to dryness. 15 The residue was dissolved in dichloromethane and purified by chromatography on silica using 5% acetone / dichloromethane as eluent followed by 20% acetone / dichloromethane as eluent. The major green fraction was collected and re-purified by chromatography on silica using 5% acetone / dichloromethane as eluent. The major green fraction was collected and recrystalized from dichloromethane / hexane. Yield, 67mg 20 Various compounds comprised essentially of a non-radioactive indium atom complexed with the inner nitrogens of a pyrrolic core have been evaluated biologically as photosensitizers. The results of some of this evaluation are summarized below.

WO 00/00204 PCT/US98/13601 18 In Vitro Biological Evaluation of Functionalized Benzochlorins. The in vitro biological evaluation of certain photosensitizers was determined, using standard procedures. Several of the photosensitizers had the following structure: R4 5 R3- \ R6 N N R2 N' N 1 / R7 5 where each of RI through R8 was ethyl and R and M had various meanings The identities of a first group of the compounds tested, all of which had the foregoing structure, of an arbitrary "Sensitizer Number" assigned for reference purposes, 10 and the Example (if any) where their preparation is described are set forth below: WO 00/00204 PCT/US98/13601 19 Sensitizer Example Identity of Identity of R in Foregoing formula Number (if any) M in Foregoing formula 1 2H H 2 2H SONH(CH,),OH 3 2H CH, 4 Zn H 5 Zn SONH(CH),OH 6 Sn H 7 Sn SO,NH(CH,),OH 8 Sn CH, 9 5 In H 10 6 In SO,NH(CH),OH 11 In CH 12 In SON(CHCHOH), 13 In SO,NH(CH,),OH 14 In See structure below 15 In See structure below 16 In SO,NH(CH,),O(CH,),O(CH;),OCH, 17 7 In SON [(CH,),O(CH,),O(CH,),O(CH,)OCH], 18 In SO,NH(CH,),SH 19 8 In See structure below 20 In SO,NHCH,COH 21 9 In See structure below

SN(CH

3

)

2 Sensitizer Number 14 SO2N =< N(CH 3

)

2 Sensitizer Number 15 SO 2

NHCH

2

CH

2 N OH Sensitizer Number 19 SO3NH OH "EOH

NH

2 Sensitizer Number 21 SO 2

NH(CH

2

)

4

CHCO

2 H The identities of a second group of compounds tested, all of which had the following structure, of an arbitrary "Sensitizer Number" assigned for reference purposes, and the Example, (if any) where their preparation is described are set forth below: WO 00/00204 20 PCT/US98/13601 R1 N' -H H20 H2

CH

3 02C Sensitizer Example Identity of Identity of R1 Number (if any) M in fore- in foregoing 5 going formula formula 22 2H Vinyl 23 SnC1 2 Vinyl 10 24 InCl Vinyl 25 InCI Ethyl 15 26 10 InCl

COCH

3 27 11 InCl CHO 28 12 Pd

COCH

3 20 WO 00/00204 21 PCT/US98/13601 A third group of the sensitizers had the folowing formula: RI N"' N/ NXN H2 R2

CO

2

CH

3 H2

CH

3 0 2 C 5 Sensitizer Example Identity of Identity of R1 Identity of R2 Number (if any) M in fore- in foregoing in foregoing going formula formula formula 29 a mixture of Vinyl CH 2

CO

2

CH

3 10 In" 113 Cl and in 1 5 Cl 30 a mixture of Ethyl

CH

2

CO

2

CH

3 15 In 11 3 Cl and In 5 Cl 20 31 a mixture of Vinyl

CO

2

CH

3 InI 13 Cl and Inl 15 Cl 25 32 a mixture of Ethyl

CO

2

CH

3 In" 11 3 Cl and In 5 Cl 30 For the Biological Evaluation, Chinese hamster lung fibroblasts (V-79) obtained from the American Tissue Culture Collection were grown in D-MEM supplemented with 10% fetal calf serum at 37 0 C, 5% CO2, and 95% humidity. These cells were used to WO 00/00204 22 PCT/US98/13601 evaluate the sensitizers for dark and light toxicity, and cellular uptake. Medium was replaced with 5% fetal calf serum supplemented medium during sensitizer incubations. In the first phase, the combination of intracellular and extracellular concentration of photosensitizer required for lethal damage to 50% of the cells in culture (DC(50)) on 5 light exposure was determined by plating cells at a density of 100 cells / cm 2 and incubating for 1-3 hours to allow attachment of the cells. Cells were incubated with various concentrations of sensitizer ([C]= 0.01-1.0pM) delivered in non-toxic concentrations of DMSO/ 5% dextrose solution or in some cases in egg yolk phosphatidase (EYP) for 16-24 hours. The cells were then irradiated with laser light using 10 a tunable Lexel argon pumped dye laser at the band I absorption of the photosensitizer. Total power density was adjusted to 12.5 mW/cm 2 and a total light dose of 1.25 J/cm 2 was applied. After treatment, cells were washed with HBSS, refed with 10% FBS supplemented DMEM with phenol red and incubated for 3-5 days to allow colony formation. Cells were fixed in methanol, stained with Giemsa, and colonies were counted. 15 Plating efficiency was determined using a control colony and the mean percent survival fraction plotted against the sensitizer concentration and the DC50 established (Table 5). Several photosensitizers were screened by a standard cellular uptake protocol. A 10pM stock solution of photosensitizer in EYP was prepared by dilution of the photosensitizer stock (1mM) using 5% dextrose solution. Monolayer V-79 cells in the log 20 phase of growth in 12- well tissue culture plates were incubated with 0.2mL of the 10pM solution of photosensitizer for time periods of 0, 12, 36, 48hrs. Following incubation the cells were washed with PBS (lmL) three times, then washed with HBSS (lmL) and detached using 100pL of trypsin. Individual wells containing cells were lysed by three freeze thaws. 25 Spiking experiments were performed to confirm that the sensitizer could be adequately recovered using standard procedures. The sensitizer was then extracted from the cell debris with DMSO, centrifuged and the supernatant examined for fluorescence. Sensitizer concentration was determined by comparison to a standard curve. Results are expressed in ug / ug protein. Untreated monolayers are used to determine cell count. 30 Treated cells of each time point were used to determine the protein concentration using the BCA assay. The results for the photosensitizers studied are presented in Table 2. Results shown are the mean of the three experiments for each timepoint.

WO 00/00204 23 PCT/US98/13601 As can be clearly seen for the compounds tested, indium compounds had clearly a much lower DC(50)(light) values, regardless of the functionality attached to the chlorin. In Vivo Assay of Photosensitizers on Tumors 5 Female C3H/HeJ mice (8-9 weeks old) were subjected to trochar implantation of BA mammary carcinoma on the hind leg of the animals. Animals having tumors ca 5mm in diameter were entered into the in vivo screen. For each new photosensitizer, a group of at least three mice were used to ascertain a drug dose that caused a response as described 10 in table 3 when treated with the appropriate wavelength of light. Generally in this series, animals were injected with I t mole of sensitizer / Kg of body weight, formulated in egg yolk phosphatidate (EYP), via the tail vein. At a defined time period later the animals were irradiated with light from a laser source tuned to the wavelength of activation of the sensitizer. The power density of the laser was set at 75mW / cm 2 with a total light dose of 15 200J / cm 2 . The spot size was lcm diameter. Results for each photosensitizer are shown in Table 3. Selected Kaplan-Meier curves for two different benzochlorin metal classes are shown below. The curves are identified by legend.

WO 00/00204 24 PCT/US98/13601 Table 2. Photophysical measurements, DC(50)(light) and cellular uptake of Photosensitizers Compound ?max # f DC (50) (light) Cellular uptake (24hrs) (Figure 16) (s M' cm ) (pM) (pmole/pg protein) (1) H2 658 (35,000) 0.347 >1.0 (4) Zn 678 (57,000) 0.150 >1.0 (6) Sn 691 (54,000) 0.044 0.08-0.16 0.501 (9) In 691 (53,000) 0.028 0.1 0.336 (2) H2 665 (34.000) 0.230 0.5-1.0 0.129 (5) Zn 678 (48,000) 0.124 0.5 -1.0 0.093 (7) Sn 684 (52,000) 0.040 0.5 -1.0 (10) In 684 (52.000) 0.027 0.1-0.125 (3) H2 658 (35.000) 0.35 (8) Sn 694 (50.000) 0.02 (11) In 687 (54,000) 0.034 (12) In 684 (52,000) -0.03 0.04 (13) In 684 (52,000) -0.03 0.04 (14) In 684 (52,000) ~0.03 0.05 (15) In 684 (52,000) -0.03 0.05 (16) In 684 (52,000) -0.03 0.04 (17) In 684 (52,000) -0.03 0.04 (18) In 684 (52,000) -0.03 0.04 (19) In 684 (52,000 -0.03 0.04 (20) In 684 (52,000 -0.03 0.04 (21) In 684 (52,000 -0.03 0.04 (22) H2 666 (45,000) (23) Sn 658 (74.000) - >1.0 (24) In 666 (45,000) (25) In 655 - 0.03 (26) In 672 0.06 (27)In 683 0.05 (28) Pd 653 - 0.05 (29) In 641 - 0.05 (30) In 637 - 0.06 (31) In 650 0.08 (32) In 642 - 0.07 WO 00/00204 25 PCT/US98/13601 Table 3 5 Tumor cure rates for free base, Zinc, Tin and Indium Chlorins Compounds Drug Dose Time of Treatment Light Dose % Cure (30 days) (Figure 16) (M) (m / Kg) Post injection n = 10 (1) H2 3 24 200 60% (4) Zn 3 24 200 0% (6) Sn 0.75 24 200 80% (9) In 0.1 24 200 70% (2) H2 2.5 24 200 80% (5) Zn 2.25 24 200 100% (7) Sn 1.5 24 200 0% (10) In 0.1 24 200 100% (3) H2 2.5 24 200 60% (8) Sn 1.0 24 200 100% ( 11) In 0.15 24 200 90% (22) H2 10.6 3 200 50% (23) Sn 2.0 24 or 6 200 0% (24) In 0.2 6 or 8 200 80% (12) In 0.05 24 200 90% (13) In 0.075 24 200 80% (14) In 0.075 24 200 90% 15) In 0.05 24 200 100% (16) In 0.05 24 200 80% (17) In 0.075 6 200 100% (25) In 0.075 6 or 8 200 80% (26) In 0.125 8 200 90% (27) In 0.1 8 200 90% 28) Pd 0.2 8 200 80% (29) In 0.15 6 200 70% 100 80 E- E a)K 60 - 0.25unVKg (n=1 )) S -a- 0.35um/Kg (n=9) 40 --- 0.5um/Kg (n=5) C 0-x---0.75urnKg(n=1p) / 20 0 5 10 15 20 25 30 35 40 Days Post PDT Kaplan-Meier survival Curves for SnOEBC WO 00/00204 26 PCT/US98/13601 100 I I I I 80 ClN N N 40 la 0.075um/Kg (n=5) S---- 0.05um/Kg (n=3) 0----- 0.1um/Kg (n=10, 2 leth I) 20 2O 0 I I _ I 0 5 10 15 20 25 30 35 40 Days Post PDT Kaplan-Meier survival curves for InOEBC. 5 The procedures of Examples 1-12 can be modified to produce other phototherapeutic compositions according to the invention, each such composition being comprised essentially of a non-radioactive indium atom complexed with the inner nitrogens of a pyrrolic core composed of at least two pyrroles. The modification involves merely substituting an equivalent amount of the free base of another compound having a 10 pyrrolic core composed of at least two pyrroles for the methyl pyropheophorbide, the benzoporphyrin derivative, the tetrakis (3-hydroxyphenyl)chlorin, the octaethylbenzo chlorin of Examples 1, 3, 4, 5, and 6 or for the corresponding starting materials of Examples 7-12, or by substituting other dicyano compounds capable of forming functionalized phthalocyanines, functionalized naphthocyanines or the like for the 4-tert 15 butyl-1,2-dicyano benzene of Example 2. Examples of compounds having a pyrrolic core composed of at least two pyrroles, and which can be substituted as described in the preceding paragraph to produce additional compounds according to the instant invention are named in Table 1, and defined by reference to Figures 1-58, which follow the Table. 20 WO 00/00204 27 PCT/US98/13601 Table 1: Pyrrole-derived macrocyclic compounds (Fig. 1). Naturally occurring or synthetic porphyrins and derivatives thereof (Fig. 2) 5 Naturally occurring or synthetic chlorins and derivatives thereof (Figs. 3, 16, 17, 32-35 and 48-55) Bacteriochlorins and isobacteriochlorins (Figs. 4, 5 and 36-47)) Phthalocyanines, Naphthalocyanines and derivatives thereof (Figs. 6, 7, 15, 18 21. 24, 26, 29, 30, 31 and 56) 10 Porphycenes and derivatives thereof (Fig. 8) Porphycyanines and derivatives thereof (Fig.9) Pentaphyrins, sapphyrins and derivatives thereof (Figs. 10 and 11) Texaphyrins and derivatives thereof (Fig. 12) Benzochlorins and derivatives thereof (Fig. 13) 15 Chlorophylls and derivatives thereof (Fig. 14) Corroles (Fig. 58) WO 00/00204 28 PCT/US98/13601 R3 R11 R4 R3 RII R4 R3 R7 R4 R2 5 R2 \ R5 R2 - ,\. R N, N, N NRIO M / R2 RI0 M R12 RI M R6 N N N N R9 R RI \ / R6 RI /R6 R9 R8 R8 R9 R7 R8 R9 R7 FIGURE 1 FIGURE 2 FIGURE 3 R3 R6 R4 R5 3 Rll R4 R3 RIl R4 R2 N R7 P3 R11 R4 N I \2 R5 R2 /R5 RI \ ,N R8 R2--5I N N N N NNM N RIO M RI2 RIO M RIM 12 N /N N N N N / N N RI6 \ R9 RI /\ R6 RI -, / R6 \ N / RI5 RIO R8R 7R8 RgR7R1R2 RI R8 R9 R7 8RI4 R13 Rll FIGURE 4 FIGURE 5 FIGURE 6 R4 R8 R9 R5 R8 R3 R6 R7 RIO R3 RlIlR2 R4 R2 \ N Rll RI .NN N R12 N N N N ,M R24 N

'

N N R13 N N RI-- /R6 R23 N 1\ R4 RR SR8 9 RIO R7 R22 R19 R18 RI5 R21 1 RI7 R16 R21 FIGURE 7 FIGURE 8 R4 R5 R4 R5 R3 Rll R13 R4 P3 RI Rl -- RII 2 N N NH R6 NH N \ R6 m m 12 MN IM-N RIO MM / RI2 M-N R7 N , N NR7 RI R7 RI /R6 RI 9 9 RIO R8 R9 R 5 R 7 R8 RIO - R8 R13 R8 R13 FIGURE 9 FIGURE 10 FIGURE 11 WO 00/00204 29 PCT/US98/13601 R4 R5 R4 R13 R5 R4 R13 R5 llR 'R R 17 N RI2 R3 R6 R3 R6 RI6 N \ R6 N, IN-, 1M-N R2 M / R14 R12 M / R14 RI N N RI N N R 15 N / R7 / R7 , / R7 R4 " 9 R21 R2 RIO - / R8 1Rl R9 8R O R13 R8 R9 RIO FIGURE 12 FIGURE 13 FIGURE 14 R4 R5 R4 R13 R5 R4 RI3 R5 N R3 R6 R3 N R6 R3 R6 RN N N N N R2 M / R14 R2 R4 N m N RI N N RI N N N / R7 \ / R7 R2 \ R7 R2 R2 NR R8 R8 RI R8 R IO 9 R 10I R9 RIO R9Rio R1 6 R1 5 FIGURE 15 FIGURE 16 FIGURE 17 R3 R4 R5 R6 R4R3 R4 R3 R3 R4 R5 R6 R3 R4R RY R18 \x64vU"

XVR

7 V R5 R2 R2-U V-R7 RN2-2 2 R2 N R8 RI N N- RI RI N N R8 N M\ N N M N N X N RI7 R9 RI N N N R R7 N N R9 RI / X N' l X, ' N' / / N R ,I-6V xx " U-I RI6-V X N ,U-RIO R2 R2 -RIO

R

- X . / v "R4 R4" 5 R4 R3 tl 15 RI4 R13 il R3 R4 R4 R3 I15 R14 R13 Rl FIGURE 18 FIGURE 19 FIGURE 20 R4 R4 R4R R5I R5 R8, R3 / R6R7R R3 R3-A BC R6 R7 D B-RIO R/,R6 R7 ' E C R2 R2 R2 N RII RI I RI R12 N\NN N N \ N N' R24 N N R13 RN R R23 E N R R14 R2 \ N'2F \ /R2 \ L C FN F_ - R R-R6 R R. B / R19 R18 ,Z ARI R3 R3 R22- \A D, /C. z:13 R5 R5 I R20 R17 RI6 R5 R5 R4 R21 FIGURE 21 FIGURE 22 WO 00/00204 30 PCT/US98/13601 R9 R4 R8, R 0 0 R3 / R6 R7 \ RIO X R2 R3 X A / D- -B A R2 0 \/ 0 D N C\ A N B. S*N R12 RA N NR4 N\ N .M\ IN N\ MX ,N S4 N N RI3 4 N R5 R22 R19 RI / R15 R7 R6 R20 0 0 R21 RI6 FIGURE 23 FIGURE 24 R4 R9 SR5 R8 I R4 R9 3RE N 'E N RRIO R --F R6 R7 E-RI4 Rl R3-D R3-D R7 E-R1O R C _ e - B A - F I I aR2 N B- N R I RN5 R12N A3-' R R7R3-RR RI NR -N N R12

N

X M\ ,N N M\ ,N R2k N N / R13 R A N N R 2 I RII R2 E

~

RN B 13 N RR 14 \C B\ B ,bl R 19-D \,. N B D-RI4 R20 /F E I R17 R16 I R17 1 R18 R15 R16 FIGURE 25 FIGURE 26 R4 R4 R5 DER5 R3-DE" R R R3-C' "x R8 R9 -CF-R6 R \7 BI I B A DR9 A B R2' R2-Bk N'p-RIO - y A N / S N N , RIO RI N N F Ni N N R11 N M\ N R24 N\ ..M N R12 R2( N N R23 R 1 2 N\ K N22R-D2 .I N \) N " . R13 RI~ ~ _ / R12

F

R9-C C, BB : c R22-D N '"R1 DI 1B- -RI 4 R15 P R20

E

R17 FIGURE 27 FIGURE 28 WO 00/00204 31 PCT/US98/13601 R7 Rl1 C- BR 6 RJB-c RI2 RA D-R8 D A 13 R3 R4 R5 R6 R4 oDR8D RI3 R9 - A R2U/ Y R18 X U -R 7 R3-C" \ .NN N D "C-R14 R2 \ -B_ x -Y R23, \ N, ,\ 1/" IRI .N N R8 RI N N R6 R-32 N\ R17 KN / M , R3 N N RI8 R17 N N R9 R30-CN \ N-- N\ R N "A R24 A// RI 6 4'- X , -yIU-RIO R29 D R20 I RI4 RI3 Rll A, " -- R25 % A-R21 R15 R28' "C -B /Bc I R26 R23 22 R27 R22 FIGURE 29 FIGURE 30 R1 R5 RI R5 RI R5 RI R4 N N N N N N N, N R3 / R3 M R3 M / R3 / H N N H N N H N N H N N H H R6 H R6 H R2 R4 X R2 R4 R2 R2 FIGURE 31 FIGURE 32 FIGURE 33 FIGURE 34 R1 R5 R 6 RI R5 R R5 R RR 6 R1 R4 R5 R7 R7 R7 R6 N, N N, N N7 N N N R3 ,M\ / R3 ,M / R3 ,M / R3 / N N N N N N N N H H H H H H R8 H R8 H R2 R4 X R2 R4 R2 R4R FIGURE 35 FIGURE 36 FIGURE 37 FIGURE 38 RI R5 R6 R R5 R6 RI R5 R6 R1 R4 R5 R 3 R6 R 3 -6 R 3 N, N- N\ N N N N, N R3 \ , / R3 M\ / R3 ,M / R3 \/ SN N N N N N N N H H / H H H H R7 H R7 H R4 A X B R4 X R4 R2 R4 X R2 R4 R2 R2 FIGURE 39 FIGURE 40 FIGURE 41 FIGURE 42 WO 00/00204 32 PCT/US98/13601 RI R7 RI R5 RI R5 RI R4 R6 R6 R6 R5 N, ,N N, N- N N N N R3 / R3 M / R3 M / R3 M / N N N N N N N N H H / H \/ H ,- H H H R7 H R7 H R RX R4 A X B R2 R R2 R4 R2 R2 FIGURE 43 FIGURE 44 FIGURE 45 FIGURE 46 R3 R3 R3 RI R13 R3 RI RI3 R4 R4 R2 RI R4 R2 R4 R2

R

2 R3IR R13R2R " 2 R5 RB3 R5 B R5 B R5 "_ N, IN- B\ IC- N\ N _ \C R6-A M C-RI2 R6 M / RI2 R6-A M, C-R 2 R6 ,M, / RI2 N' CR2R A mD R2N' N AI 'D R7 D,- RiI R7 - / R II R7 p, Rl R7 D / R l R8 R9 RIO R8 R9 RIO R8 R9 RIO R8 R9 RIO FIGURE 47 FIGURE 48 FIGURE 49 FIGURE 50 RI5 RI RI3 RI5 RI RI3 D'II RR 5 R1 R3 RI R3 R3 RI R13 R3 R3 I RI R2R4 R2 R4 R2 R14 R4 R2 4 ' R2 R R5 R5 R 5 B C R5 B N~ N_ R6 \ M / R12 R6A M C-R2 R6 ,M / R2 R6-A M, C-R12 AR D N "N A " : D NN R7 /RII R7 D RII R7 I /RlI R7 I / RII R8 R IO 2 N R9 RIO R8 R9 RIO R8 R9 RIO R8 R9 RIO FIGURE 51 FIGURE 52 FIGURE 53 FIGURE 54 1R4 R3 EF, R8R43 R4 I RI R3-DE R4 R3 RI B c \C-R R5 R13 p N R5 R13 N N A ~N 1 N,, 1 R6A NR N~- RIO N\ N RC-R12 N N ,M / R12 N / RR N ~j R R7 D R RI / 1 R7 \NN /RII R8 R9 RIO CB BC R8 R9 RIO R16 'Rl5 R14 Il3 FIGURE 55 FIGURE 56 FIGURE 57 WO 00/00204 PCT/US98/13601 33 Examples and illustrations from the literature outlined in Table I and Figures 1 to 57 of types of photosensitizers that may be used in photodynamic therapy or imaging and are applicable to the insertion of indium into the central core are as follows: Dipyrromethenes: (Figure 1). 5 Dipyrromethenes have been used widely as intermediates in. the synthesis of porphyrins (for example "The Porphyrins" Ed. D.Dolphin, Academic Press, 1978, Volume II. 215-223; Volume I, Chapter IV, 101-234. References within these volumes provide actual experimental details. These compounds can be coordinated with metal salts to produce metallo complexes (for example A.W. Johnson, I.T. Kay, R. Price, K.B. Shaw, J. 10 Chem. Soc, Perkin Trans I, 3416-3424, 1959; S.M. Bloom, P.P. Garcia; J.H. Boyer, L.R. Morgan US Patent 5,189,029; date of patent Feb 23, 1993; L.R. Morgan, J.H. Boyer, U.S Patent 5,446,157). As shown in Figure 1, these molecules can be synthesized such that a wide variety of functionality can be directly attached to the basic diyrromethene ring structure. Such functionality can be used to increase water solubility, lippophilicity, 15 conjugation to biomolecules such as antibodies or proteins, to increase the wavelength of absorption of the molecules (by increasing the conjugation of the macrocycle). As such, these molecules can be used for light activated photochemistry or diagnosis. Porphyrins: (Figure 2) Routes to the synthesis of the ubiquitous tetrapyrrolic macrocycles that contain in 20 their macrocyclic ring system 11 double bonds (excluding peripheral substituents), is outlined in detail in several books including "Porphyrins and Metalloporphyrins" Ed. K.M. Smith, Elsevier Publishing Company, New York, 1975, Chapter 2, p29-55; chapter 19, p 7 7 8

-

7 8 5 and "The Porphyrins" Ed. D.Dolphin, Academic Press, 1978, Volume I. References within these volumes provide actual experimental details. A very large number 25 of porphyrinic compounds have been synthesized. As they are prevalent in nature, a large number of studies on the chemical modification of these compounds have been undertaken ("The Porphyrins" Ed. D.Dolphin, Academic Press, 1978, Volume I, p 289-339.). A great deal of work has been undertaken on the synthesis of porphyrins from mono-pyrrols ("The Porphyrins" Ed. D.Dolphin, Academic Press, 1978, Volume I, chapter 3, 85-100; chapter 30 4, 101-234, chapter 5, 235-264; chapter 6, 265-288). Notable valuable examples of such work is in the synthesis of mono, di, tri and tetraphenyl porphyrins ("The Porphyrins" Ed. D.Dolphin, Academic Press, 1978, Volume I, chapter 3, 88-90; Gunter, M.J., Mander, L.N., J. Org. Chem. 46, 4792-4795, 1981.). Such compounds can be widely functionalized WO 00/00204 PCT/US98/13601 34 as the aromatic rings may possess different substituents or have incorporated in them heteroatoms. Porphyrins also can be synthesized that possess annelated aromatic rings on the P3-pyrrole positions (T.D. Lash, C.Wijesinghe, A.T. Osuma, J.R. Patel, Tetrahedron Letters, 38(12), 2031-2034. 1997.) which can have the effect of extending conjugation and 5 modifying the absorption and photophysical properties of the compounds. Porphyrin type compounds have been synthesized from pyrroles and 5-membered ring heterocycles (such as thiophenes or furans for example) which incorporates one or more heteroatom besides nitrogen within the central porphyrin "core" ("Porphyrins and Metalloporphyrins" Ed. K.M. Smith, Elsevier Publishing Company, New York, 1975, Chapter 18, 729-732). Such to compounds can be modified similarly to produce highly functionalized derivatives. In addition porphyrin dimers, trimers or oligomers have been synthesized with great abandon.( H. Meier, Y. Kobuke, S. Kugimiya, J. Chem. Soc. Chem. Commun., 923, 1989; G.M. Dubowchik, A.D. Hamilton, J. Chem. Soc. Chem. Commun.,904, 1985; R.K. Pandey, F-Y. Shaiu, C.J. Medforth, T.J. Dougherty, K.M. Smith, Tetrahedron Letters, 31, 15 7399, 1990; D.R. arnold, L.J. Nitschinsk, Tetrahedron Letters, 48, 8781, 1992; J.L. Sessler, S. Piering, Tetrahedron Letters, 28, 6569, 1987; A. Osaku, F. Kobayashi, K. Maruyama, Bull. Chem. Soc. Jpn, 64, 1213, 1991). Chlorins: (Figures 3, 16, 17, 31-34, 47-54) Chlorins or Hydroporphyrins are porphyrins that have only 10 double bonds in 20 their macrocyclic ring system (excluding peripheral substituents). The "reduction" of the porphyrin macrocycle has pronounced effects on both the absorption profile of the macrocycle and the photophysical properties of the compound. Many naturally occuring chlorins may be extracted from plants, seaweeds or algae (e.g. "Porphyrins and Metalloporphyrins" Ed. K.M. Smith, Elsevier Publishing Company, New York, 1975, 25 Section H, p 7 74 -778.) and simple chemical modifications to pheophorbide can give pyrropheophorbides, chlorin e6, purpurin 18 and other chlorin ring systems. Routes to the synthesis of chlorin macrocycles are outlined in "Porphyrins and Metalloporphyrins" Ed. K.M. Smith, Elsevier Publishing Company, New York, 1975, Chapter 2, p 6 1

-

1 16; Chapter 19, 774-778, "The Porphyrins" Ed. D.Dolphin, Academic Press, 1978, Volume II, pl-37, 30 p 13 1-143. References within these volumes provide actual experimental details. Considerable research has been directed toward the synthesis of chlorin derivatives from porphyrins. Catalytic hydrogenation and hydroboration (H.H. Inhoffen, J.W. Buchler, R. Thomas, Tetrahedon Letters, 1145, 1969;.), diimide reductions (H.W. Whitlock Jr., R WO 00/00204 PCT/US98/13601 35 Hanauer, R., Oester, m.Y., B.K. Bower, J. Am. Chem. Soc. 91, 7585, 1969), osmium tetroxide (R. Bonnett, A.N. Nizhnick, M.C. Berenbaum, J. Chem. Soc. Chem. Comm., 1822, 1989) and hydrogen peroxide (C,K, Chang, Biochemistry, 19, 1971, 1971.) , alkali metals and electrochemical reduction (N.S. Hush, J.R. Rowlands, J. Am. Chem. Soc., 89, 5 2976, 1967), aromatic radicals ( G.L. Closs, L.E. Closs, J. Am. Chem. Soc, 85, 818, 1963) have all been successful at producing chlorins from porphyrins. The use of light as a reductive tool has also been extensively studied by several authors. The reaction of singlet oxygen on vinyl porphyrin has been used extensively to produce chlorins (H.H. Inhoffen, H. Brockman, K.M. Bleisnerv, Ann. Chem. 730, 173, 1969; D. Brault, C. Vever-Bizet, 10 Mougee, C., Bensasson, R., Photochem. Photobiol., 47 151, 1988). The reduction of free base and metalloporphyrins with light and and reducing agents (such as amines or ascorbates) (Y. Harel, J. Manassen, J. Am. Chem. Soc., 100, 6228, 1977; J.H. Fuhrhop, T. Lumbantobing, Tetrahedron Letters, 2815, 1970; D.G. Whitten, J.C., Yau., F.A. Carol, J. Am. Chem. Soc., 93, 2291, 1971.) also produces chlorins. Cyclization of meso-acrylate 15 containing porphyrins has been used extensively to produce purpurin derivatives (Figure 16 and 17) (A.R. Morgan, N.C. Tertel., J.Org. Chem., 51, 1347, 1986) while acid cyclization of meso-acrolein porphyrins has been used extensively to produce benzochlorins (Figure 13.) ( M.G.H, Vincente, I.N. Rezzano, K.M. Smith, Tetrahedron Letters, 31, 1365, 1990; M.J. Gunter, B.C. Robinson, Tetrahedron., 47, 7853, 1991). Diels 20 alder addition of dienophiles with vinyl containing porphyrins has been used extensively to produce chlorins ( Figures 49-54) (R. Grigg, A.W. Johnson, A. Sweeney, Chem. Commun., 697, 1968, H.J. Callot, A.W. Johnson, A. Sweeney, J. Chem. Soc. Perkin Trans. I, 1424, 1973; V.S. Pangka, A.R. Morgan, D.Dolphin J.Org. Chem. 51, 1094, 1986; P. Yon-Hin, T.P. Wijesekera, D.Dolphin, Tetrahedron Letters, 32, 2875, 1991; P. Yon 25 Hin, T.P. Wijesekera, D.Dolphin, New. J. Chem, 16, 527, 1992; A.R. Morgan, D.Skalkos, G.M. Garbo, R.W. Keck, S.H. Selman J. Med. Chem. 34, 1991). Acetamidoporphyrins can be cyclized to produce chlorins via a intramolecular Vilsmeier reaction (G.L. Collier, A.H. Jackson, G.W., Kenner, J. Chem. Soc., C., 564, 1969). Recently, chlorin analogues of Purpurin 18 based on purpurin 18, have been produced that possess nitrogens on the cyclic 30 "anhydride" ring system (Figure 35, A or B = NR) (A.N. Kosyrev, G. Zheng, E. Lazarou, T. J. Dougherty, K.M. Smith, R. Pandey, Tetrahedron Letters, 38, 3335, 1997).

WO 00/00204 PCT/US98/13601 36 Bacteriochlorins and isobacteriochlorins: (Figures 4, 5, 35 to 46) Bacteriochlorin and isobacteriochlorins are tetrahydroporphyrins. These derivatives have only nine double bonds in their macrocyclic ring system (excluding peripheral groups). The "double" reduction of the porphyrin nucleus at the pyrrole 5 positions has a pronounced effect on the absorption properties and photophysical properties. Typically bacteriochlorins absorb in the 720-850nm range while isobacteriochlorins absorb in the 500-650nm range ("The Porphyrins" Ed. D.Dolphin, Academic Press, 1978, Volume III, Chapter 1; References within these volumes provide actual experimental details). Examples of the synthesis of bacteriochlorins and 10 isobacteriochlorins may be found in the following references; H, H Inhoffen, P. Jager and R. Mahlhop and C.D. Mengler, Justus Liebigs Ann. Chem. 704, 188, 1967; H, H Inhoffen, P. Jager and R. Mahlhop and C.D. Mengler, Justus Liebigs Ann. Chem. 704, 188, 1967; H. Mittenzwei, Hoppe-Seyler,s Z. Physiol. Chem. 275, 93, 1942; H. Brockmann Jr., G . Knobloch, Arch. Mikrobiol, 85, 123, 1972; J.J. Katz, H.H., Strain, 15 A.L., Harkness, M.H. Studier, W.A., Svec, T.R. Janson, B.T. Cope, J. Am. Chem Soc. 94, 7983, 1972; D. Dolphin C. Bruckner, Patent No: 5,648,485, Date of Patent Jul. 15, 1997; D. Dolphin, P.Y. Hin, T. Wijesekera Patent No: 5,149,708, Date of Patent: Sept 22, 1992; H.W. Whitlock, R. Hanauer, M.Y. Oester, B.K. Bower, J. Am. Chem Soc. 91, 7485, 1969; H, H Inhoffen, H. Sheer, Tetrahedron Letters, 1115, 1972; H, H Inhoffen, J.W. Buchler, R. 20 Thomas, Tetrahedron Letters, 5145, 1969; J.H. Fuhrhop, T. Lumbantobing, Tetrahedron Letters, 2815, 1970; A. Scherz, Y. Saloman, L. Fiedor European patent No: 0584,552 A2: A. Scherz, Y. Saloman, L. Fiedor U.S patent No: 5,650,292; (A.N. Kosyrev, G. Zheng, E. Lazarus, T. J. Dougherty, K.M. Smith, R.Pandey, Tetrahedron Letters, 38, 3335, 1997). In particular, osmium tetroxide has proved useful in the synthesis of 13,P 25 dihydroxy-bacteriochlorins and isobacteriochlorins from chlorins (R.K. Pandey, T.J. Dougherty, K.M. Smith, F.Y. Shiau, U.S. Patent No: 5,591,847) and the acid rearrangement of these derivatives has produced numerous bacteriochlorin derivatives. The treatment of porphyrins and chlorins with hydrogen peroxide has been used to produce bacteriochlorins and isobacteriochlorins (H.H. Inhoffen, W. Nolte, Justus Liebigs 30 Ann. Chem. 725, 167, 1969). Diels alder addition of dienophiles with porphyrins containing two P3-vinyl substituents has been used extensively to produce bacteriochlorins and isobacteriochlorins (R. Grigg, A.W. Johnson, A. Sweeney, Chem. Commun., 697, 1968, H.J. Callot, A.W. Johnson, A. Sweeney, J. Chem. Soc. Perkin Trans. I, 1424, 1973.; WO 00/00204 PCT/US98/13601 37 P. Yon-Hin, T.P. Wijesekera, D.Dolphin, Tetrahedron Letters, 32, 2875, 1991; A.R. Morgan, D.Skalkos, G.M. Garbo, R.W. Keck, S.H. Selman J. Med. Chem. 34, 1991). Phthalocyanines and Naphthalocyaninesl (Figure 6, 18, 21-24, 28-30) Phthalocyanines and phthalocyanine analogues are perhaps some of the most 5 widely studied photosensitizers in the field of photodynamic therapy and are also widely used as optical recording media. As such the number of structurally different phthalocyanine derivatives is enormous. Not only can the peripheral functionality be widely varied which changes the electronic spectra and photophysics of the compounds, but metallation of the macrocycle also results in photophysical changes. In addition 10 carbons in the aromatic rings may be substituted with heteroatoms (such as nitrogen, sulphur phosphorus) that change markedly the photophysical properties of the compounds. Examples of references that disclose the formation of such compounds are; "Phthalocyanines Properties and Applications, Eds. C.C. Leznoff, A.B.P. Lever, VCH Publishers Inc., 1989; "The Phthalocyanines", Eds, F.H. Moser, A.L. Thomas, CRC Press, 15 Volumes I and II, 1983; "The Porphyrins" Ed. D.Dolphin, Academic Press, 1978, Volume I, Chapter 9, p 374-380, References within these volumes provide actual experimental details; A.K. Sobbi, D.Wohrle, D. Schlettwein, J. Chem. Soc. Perkin Trans. 2, 481-488, 1993; J.H. Weber, D.H. Busch, Inorg. Chem. 192, 713, 1988.; R.P. Linstead, F.T. Weiss, J. Chem. Soc., 2975, 1950; M.E. Kenney, N.L. Oleinick, Patent No: 5,166,197, date of 20 patent Nov 24, 1992; M.E. Kenney, N.L. Oleinick, Patent No: 5,484,778, date of patent Jan 16, 1996; P. Gregory, S.J. Reynolds, R.L. White, Patent No: 5,484,915, date of patent: Jan 16, 1996. A great number of binuclear phthalocyanines / napthalocyanines have been synthesised which share a common benzene or naphthalene ring (J. Yang, M.R. Van De Mark, Tetrahedron Letters, 34, 5223, 1993; N. Kobayashi, HY. Higashi, T. Osa, 25 Chemistry letters, 1813, 1994. Azoporphyrins: (Figures 18, 20, 21, 30, 55) Porphyrins that possess at least one meso-nitrogen linking atom are called azoporphyrins. The number of meso-nitrogen linking atoms may be extended from one to four. Phthalocyanines and Naphthalocyanine may be regarded as tetraazoporphyrins with 30 extended conjugation due to annelated benzene and napthalene rings. The synthesis of mono, di, tri and tetraazoporphyrin analogues is discussed in "The Porphyrins" Ed. D.Dolphin, Academic Press, 1978, Volume I, Chapter 9, p 365-388; "Phthalocyanines Properties and Applications, Eds. C.C. Leznoff, A.B.P. Lever. VCH Publishers Inc., 1989; WO 00/00204 PCT/US98/13601 38 "The Phthalocyanines", Eds, F.H. Moser, A.L. Thomas, CRC Press, Volumes I and II, 1983. References within these volumes provide actual experimental details. The synthesis of a series of tetrabenzotriazoporphyrins and tetranapthotriazoporphyrins has recently been published (Y-H, Tse, A. Goel, M. Hue, A.B.P. Lever, C.C. Leznoff , Can. J. Chem. 71, 5 742, 1993.) and clearly it can be envisaged that chemistry typical of phthalocyanine chemistry and porphyrin chemistry may be applied to these compounds, such that hetero atoms may be introduced into the annelated benzene or napthalene rings. Unsymmetrical benzonaphthoporphyrazines (Figures 25-27, 57 ) Unsymmetrical tetraazoporphyrins that have both a benzene and a naphthalene 10 annelated unit in the macrocyclic ring system are loosely called benzonaphthoporphyrazines. The synthesis of these derivatives is carried out using classical phthalocyanine syntheses however, using mixed aromatic dinitriles (U. Michelsen. H. Kliesch, G. Schnurpfeil, A.K. Sobbi, D. Wohrle, Photochem. Photobiol, 64, 694, 1996; S.V. Kudrevich, H. Ali, J.E. Van Lier: Canadian Patent No: 2,130,853 Filed 25 15 / 8/ 1994). References to the synthesis of these macrocycles can also be found in "Phthalocyanines Properties and Applications, Eds. C.C. Leznoff, A.B.P. Lever, VCH Publishers Inc., 1989; "The Phthalocyanines", Eds, F.H. Moser, A.L. Thomas, CRC Press, Volumes I and II, 1983. Texaphyrins: (Figure 12) 20 Texaphyrins are tripyrrol dimethene derived "expanded porphyrin" macrocycles who's central core is larger than that of a porphyrin. The reaction of diformyl tripyrranes with functionalized aromatic diamines in the presence of a metal, gives rise to functionalized metallated texaphyrins (J.L. Sessler, G.W. Hemmi, T.D. Mody, U.S. Patent No: 5,252,720; J.L. Sessler, G.W. Hemmi, T. Murai, U.S. Patent No: 4,935,498; D. 25 Magda, J.L Sessler, B. Iverson, P.L. Jansen, M. Wright, T D. Mody, G.W. Hemmi, U.S. Patent No: 5,567,687). Pentaphyrins and Sapphyrins:._ (Figures 10, 11). Sapphyrins and pentaphyrins are fully conjugated macrocycles that possess five pyrrole units. Structural analogues of the sapphyrins and pentaphyrins are outlined in 30 "Porphyrins and Metalloporhyrins", Ed. K.M. Smith, Elsevier, Chapter 18, p 7 5 0

-

7 5 1; "The Porphyrins Ed. D Dolphin, Academic Press, NY, Chapter 10, p351-356; Broadherst et al, J. Chem. Soc. Perkin Trans. I , 2111, 1972; J.L Sessler, V. Kral, U.S. Patent 5,543,514).

WO 00/00204 PCT/US98/13601 39 Porphycenes: (Figure 8). Porphycenes are isomeric analogues of porphyrins that have eleven double bonds in their macrocyclic core that are derived formally by a mere reshuffling of the pyrrole and methine moieties. Routes to the synthesis of functionalized porphycenes are outlined in 5 the following references; E.Vogel, C. Richert, T. Benninghaus, M. Muller, A.D. Cross. U.S. patent 5,409,900; E.Vogel, C. Richert, T. Benninghaus, M. Muller, A.D. Cross. U.S. patent 5,262,401: E.Vogel, P.A. Koch, A. Rahbar, A.D. Cross. U.S. patent 5,244,671; E.Vogel, M. Muller, A.D., O. Halpern, Cross. U.S. patent 5,610,175; E.Vogel, M. Muller, A.D., O. Halpern, A.D. Cross. U.S. patent 5,637,608; E.Vogel, C. Richert, T. 0io Benninghaus, M. Muller, A.D. Cross. U.S. patent 5,179,120; D. Martire, N. Jux, P. F. Armendia, R.M. Negri, J. Lex, S. E. Braslavsky, K. Schaffner, E. Vogel. J. Am. Chem. Soc.. 114, 1992; N. Jux, P. Koch, H. Schmickler, J.Lex, E.Vogel. Angew. Chem. Int. Ed. Engl. 29, 1385, 1990. Corroles; (Figure 57) 15 Corroles contain an aromatic 18 electron chromophore. The synthesis and structural modifications of these compounds (such as N-alkylation) are discussed in detail in "The Porphyrins" Ed. D.Dolphin, Academic Press, 1978, Volume I, Chapter 9, p 357 363 and in "Porphyrins and Metalloporphyrins" Ed. K.M. Smith, Elsevier Publishing Company, New York, 1975, Chapter 18, p 7 3 0 -749. 20 It will be appreciated that various changes and modifications can be made from the specific details of the invention as disclosed above, and as described in the foregoing examples and that, in its essential details, the invention is a composition which is comprised essentially of a non-radioactive indium atom complexed with the inner nitrogens of a pyrrolic core composed of at least two pyrroles, with the proviso that fully 25 unsaturated porphyrins having the structures: R3 RI2 R4 R2 R5 N N\N. Rl In RIO N N RI \ R6 R9 R8 R7 WO 00/00204 PCT/US98/13601 40 where R1, R2, R4 and R6 are methyl, R8, R10, Ri I and R12 are hydrogen, and R7 and R8 are CH 2

CH

2 COR13 (where R13 is a moiety which results from the removal of H from an amino acid), and RI Me M RI N N N M, Me 0 2 R 2 C0 2

R

2 5 where RI is CH(OH)Me, R is alkyl, and R 2 is a residue derived by removing H from an amino acid are excluded. Preferably, the invention is a composition which is comprised essentially of a non radioactive indium atom complexed with the inner nitrogens of a tetrapyrrolic core, with 10 the proviso that the fully unsaturated porphyrins identified above are excluded. A non radioactive indium atom complexed with the inner nitrogens of a photosensitive compound having a dihydro or tetrahydro tetrapyrrolic core is another preferred composition of the invention. Other preferred families of compounds according to the invention have the 15 structures of Figs. I to 58, above. Specifically, one preferred family has the structure of Fig. 2, where each of R1 through R12 is H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, vinyl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, NR12R12, CN, OH, OR12, CHO, (CH 2 )nOH, (CH 2 )nSH, (CH2)nO-alkoxy, (CH,)nSR12, (CH,)nOR12 (where n = 1, 2, 3, 4, and R12 is a functional group less than or 20 equal to 100000 daltons), (CH 2 )nCO2R12 (where R12 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n=1, 2, 3, 4), (CH 2 )nCONHR12, (CH 2 )nCON(R12) 2 , CO 2 R12 (where R12 is a functional group less than or equal to 100000 daltons), SR12 (where R12 is a functional group less than or equal to 100000 daltons), SO 3 H, SO 3 R12, SO 2 NHR12, 25 SO 2 N(R12) 2 , SO 2 N(R12) 3

+

X (where RI2 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion).

WO 00/00204 PCT/US98/13601 41 Z is a halide , acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, or a functional group less than or equal to 100000 daltons, protein or biomolecule, with the exclusions noted above when the pyrrolic core is fully unsaturated. 5 Still another preferred family has the following structure: R3 14 4 R- R5 RI2 , 13 RI -R6 R9 RIO R9 8 R7 where each of RI through R14 is H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester,

C(X)

2

C(X)

3 (where X is a halogen), NR15R15, CN, OH, OR15, CHO, COCH 3 , (CH 2 )nOH, 10 (CH 2 )nSH, (CH 2 )nO-alkoxy, (CH 2 )nSR15, (CH 2 )nOR15 (where n = 1, 2, 3, 4, and R15 is a functional group less than or equal to 100000 daltons), (CH2)nCO 2 R15 (where R15 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n=1, 2, 3, 4), (CH 2 )nCONHR15,

(CH

2 )nCON(R15)2, CO2R15, CONHR15, CON(R15) 2 , (where R15 is a functional groups 15 less than or equal to 100000 daltons), SR15 (where R15 is a functional group less than or equal to 100000 daltons), SO 3 H, SO 3 R15, SO 2 NHR15, SO 2 N(Rl5) 2 , SO 2 N(R15)3'X (where R15 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion); M is In'" 3 , In 1 5 or a mixture of In' 13 and In'IS; Z is a halide, acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, or a 20 functional group less than or equal to 100000 daltons, proteins or biomolecules. M in the foregoing formula can also be Pd, Sn, Pt, Al, Ru, Ga.

WO 00/00204 PCT/US98/13601 42 Another preferred family has the following structure: R2 N M R3 R4 Where each of R1 through R4 is selected from SO 3 H (or a salt thereof), SO2NHR5, CO 2 H (or a salt thereof), CONHR5, OH, OR5 (wherein R5 is a alcohol or ether containing 5 group), amide, N(CH 3

)

2 , N(Et) 2 . M is In 11 3, In 11 5 or a mixture of In 113 and In 1 1 5 Z is a halide, acetate, OH. M in the foregoing formula can also be Pd, Sn, Pt, Al, Ru, Ga. Another preferred family has the following structure: 10 B" C' D I II A... E B=A N, N A=B C,, ,/--\ , M / 1-.-, ,,C D-E N N E-D E A D -.

C . B Where each of A, B, C, D and E is C, N, N+R (where R is alkyl charged or uncharged) or combinations thereof; M is In 1 13 In 115 or a mixture of In 1 13 and In' 15 and Z is a halide, acetate, OH. 15 M is the foregoing formula can also be Pd, Sn, Pt, Al, Zn, Ru, Ga.

WO 00/00204 PCT/US98/13601 43 Still another preferred family has the structure: R14 R12 R13 Rll RIO R15 Z R9 N, \ N R16 M / R8 N N RI \ /R7 R2 R3 R 4 R5 R6 Where each of R1 through R16 is H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, 5 substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, CH=CHCH2N(CH 3

)

2 , CH=CHCH 2

N+(CH

3 )3 X (where X is a charge balancing ion), C(X) 2

C(X)

3 (where X is a halogen), NR17R17, CN, OH, OR17, CHO, COCH 3 , CH(OR17)CH 3 , (CH2)nOH, (CH2)nSH, (CH2)nO-alkoxy, (CH2)nSR17, (CH2),OR17 (where n = 1, 2, 3, 4, and R17 is a functional groups 10 less than or equal to 100000 daltons), (CH2)nCO2R17 (where R17 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl or substituted alkyinyl, and n=1, 2, 3, 4), (CH2)nCONHR17, (CH2)nCON(R17)2,, CO2R17, CONHRI7, CONR17R17, SR17 (where RI7 is a functional groups less than or equal to 100000 daltons), 15 SO 3 H. SO 3 R17, SO2NHR17, SO 2 N(R17) 2 , SO 2 N(R17) 3 +X" (where R17 is a functional groups less than or equal to 100000 daltons and X is a charge balancing ion); M is In 11, In"' 5 or a mixture of In' 13 and In'' 5 ; Z is a halide , acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkyne, or functional groups less than or equal to 100000 daltons, proteins or biomolecules. 20 Yet another family has the structure: R2 25 M I N N R3 R4 WO 00/00204 PCT/US98/13601 44 Where each of R1 through R4 is SO 3 H (or a salt thereof), SO 2 NHR5, CO 2 H (or a salt thereof), CONHR5, OH, OR5 (wherein R5 is a alcohol or ether containing group), amide,

N(CH

3

)

2 , N(Et) 2 . M is In 113 , In' or a mixture of In' 3 and In' 5 5 Z is a halide, acetate, OH. M can also be Pd, Sn, Pt, Al, Zn, Ru, Ga. Still another family has the structure: B C'D B C D I 11 A" E \z B=A N ,N A=B Co / \ , M / \ , D-E N N E-D E A I II D.C' B 10 Where each of A-E is C, N, or N'R (where R is a charged or uncharged alkyl group); M is In 1 1 3 , In 15 or a mixture of In l3 and In'' 5 Z is halide, acetate, or OH. M can also be Pd, Sn, Pt, Al, Zn, Ru, Ga. 15 Another family has the structure: RIO RI R7 \ '>'-R4 R9 R2 N Z N- R3 \11, M R8 N N R7 R4 R6 /R Where each of R1 through R10 is H, halide, alkyl, cyclic alkyl (1-6 carbons), aryl, 20 substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester,

CH=CHCH

2

N(CH

3

)

2 , CH=CHCH 2

N+(CH

3

)

3 X- (where X is a charge balancing ion), WO 00/00204 PCT/US98/13601 45

C(X)

2

C(X)

3 (where X is a halogen), NRlIRi1, CN, OH, ORI1, CHO, COCH 3 , CH(OR11)CH 3 , (CH 2 )nOH, (CH,)nSH, (CH2)nO-alkoxy, (CH2)nSR 11 , (CH 2 )nOR11 (where n = 1, 2, 3, 4, and R11 is a functional groups less than or equal to 100000 daltons),

(CH

2

)CO

2 R 11 (where R 11 is H, a physiologically acceptable salt, alkyl (1-6 carbons), 5 aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl or substituted alkynyl, and n=1, 2, 3, 4), (CH 2 )nCONHR11, (CH,)nCON(R11) 2 , CO 2 R11, CONHR11, CONR11R11, SR11 (where R1 1 is a functional groups less than or equal to 100000 daltons), SO 3 H, SO 3 R11,

SO

2 NHR 11, SON(R 1)2, SO 3 N(R11) 3 +X- (where R11 is a functional groups less than or equal to 100000 daltons and X is a charge balancing ion); M is In 13 , In 115 or a mixture of 10 In" 3 and In'115 ; Z is a halide, acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, or a functional group less than or equal to 100000 daltons, proteins or biomolecules. M can also be Pd, Sn, Pt, Al, Zn, Ru, Ga. 15 Another family of compounds has the structure immediately above, where each of R1, R2, R6, R7 is CO 2 H (or a salt thereof), or CO 2 R 11 (where R11 is alkyl or aryl). Each of R3 and R8 is methyl or ethyl. Each of R4, R5, R9, R10 is methyl, ethyl alkyl, CH 2

CH

2

CO

2 H (or salts therof), or 20 CH 2

CH

2

CO

2 RI I (where R 1 is alkyl or aryl). M is In 11 3 In 115 or a mixture of In" 13 and In' 15 and Z is a halide, acetate, OH. M can also be Pd, Sn, Pt, Al, Zn, Ru, Ga. 25 Still another family of compounds has the structure: R10 R1 R9 R2 SN Z N- R3 3 R8 N N R7 / R4 R6 \ / WO 00/00204 PCT/US98/13601 46 Where each of R1-R10 is H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, 5 CH=CHCH 2

N(CH

3

)

2 , CH=CHCH 2 N (CH3) 3 X (where X is a charge balancing ion),

C(X)

2

C(X)

3 (where X is a halogen), NRIIR11, CN, OH, OR1, CHO, COCH 3 , CH(OR11)CH 3 , (CH,)nOH, (CH 2 )nSH, (CH,)nO-alkoxy, (CH 2 )nSR 11, (CH,)nOR11 (where n = 1, 2, 3, 4, and R Il is a functional group less than or equal to 100000 daltons),

(CH

2 )nCOR11 (where RI 1 is H, a physiologically acceptable salt, alkyl (1-6 carbons), 10 aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n=1, 2, 3, 4), (CH,)nCONHR11. (CH 2 )nCON(R11),, CO 2 R11, CONHR11, CONR 1R11, SR11 (where R 11 is a functional groups less than or equal to 100000 daltons), SO 3 H, SO 3 R1 1,

SO

2 NHR1 1, SOzN(R11)2, SO 3 N(R1 1) 3

'X

- (where R 1 is a functional groups less than or equal to 100000 daltons and X is a charge balancing ion); M is In 13, n 115 or a mixture of 15 In 1 ' 3 and In 115 ; Z is a halide, acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl; substituted alkynyl, or a functional group less than or equal to 100000 daltons, proteins or biomolecules.

WO 00/00204 PCT/US98/13601 47 Another family of compounds has the structure: RIO \R1 R9 R2 SNZ N- R3 R8 N N R7 / R4 R6\ / Where each of R1-RIO is H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, 5 alkenyl, substituted alkenyl, alkynyl, substituted alkynyil, amide, ester,

CH=CHCH

2

N(CH

3

)

2 , CH=CHCH 2

N+(CH

3

)

3 X (where X is a charge balancing ion),

C(X)

2

C(X)

3 (where X is a halogen), NR11R1I, CN, OH, OR11, CHO, COCH 3 , CH(ORl1)CH 3 , (CH 2 )nOH, (CH 2 )nSH, (CH 2 )nO-alkoxy, (CH 2 )nSR11, (CH 2 )nOR11 (where n = 1, 2, 3, 4, and R11 is a functional group less than or equal to 100000 daltons), 10 (CH 2 )nCO 2 Rll 1 (where R11 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl or substituted alkynyl, and n=l, 2, 3, 4), (CH 2 )nCONHR11, (CH 2 )nCON(R1l)2, CO2R1l, CONHR11, CONR11R11, SR11 (where R11 is a functional group less than or equal to 100000 daltons), SO 3 H, SO 3 R11,

SO

2 NHRI 1, SO 2 N(R 1)2, SO 3 N(R 11) 3

+

X (where R 11 is a functional groups less than or 15 equal to 100000 daltons and X is a charge balancing ion); M is In113, In115 or a mixture of In' 1 3 and In 115 ; Z is a halide , acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, or a functional group less than or equal to 100000 daltons, protein or biomolecule. M can also be Pd, Sn, Pt, Al, Zn, Ru, Ga.

WO 00/00204 PCT/US98/13601 48 Another family has the structure: RIO RI R9 R2 N ZN- R3 M R8 N N R7 R4 R6 ' /R5 5 where each of R1, R2, R6, R7 is CO 2 H (or a salt thereof), CO 2 R11 (where R11 is alkyl or aryl). each of R3 and R8 is methyl or ethyl. each of R4, R5, R9, R10 is methyl, ethyl, alkyl, CH 2

CH

2

CO

2 H (or a salt therof), or 10 CH 2

CH

2

CO

2 R11 (where R11 is alkyl or aryl). M is In 3, In I 1 5 or a mixture of In" 3 and In" 1 5 ; and Z is a halide, acetate, OH. M can also be Pd, Sn, Pt, Al, Zn, Ru, Ga. Yet another family of compounds has the following structure; R14 IR R2 R13 R3 N Z N- R5 R 4 M / RI1IRR 2 N N RIO / / R6 R9 /R7 R8 15 Where each of R1-RI4 is H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester,

CH=CHCH

2

N(CH

3

)

2 , CH=CHCH 2

N+(CH

3 )3 X- (where X is a charge balancing ion),

C(X)

2

C(X)

3 (where X is a halogen), NR15R15, CN, OH, OR15, CHO, COCH 3 , 20 CH(OR15)CH 3 , (CH,)nOH, (CH 2 )nSH, (CH 2 )nO-alkoxy, (CH 2 )nSR15, (CH2)nOR15 (where n = 1, 2, 3, 4, and R15 is a functional groups less than or equal to 100000 daltons), WO 00/00204 PCT/US98/13601 49 (CH2)nCO 2 R15 (where R15 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n=1, 2, 3, 4), (CH2)nCONHR15, (CH 2 )nCON(R15) 2 , CO 2 R15, CONHR15, CONR15R15, SR15 (where R15 is a functional group less than or equal to 100000 daltons), SO 3 H, S0 3 R15, 5 SO 2 NHR15, SO 2 N(R15) 2 , SO 3 N(R15) 3

X

- (where R15 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion); M is In' 1 3 , In" 5 or a mixture of In 13 and In 115 ; Z is a halide, acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, or a functional group less than or equal to 100000 daltons, protein or biomolecule. 10 Still another family of compounds has the structure: RI14 RI R2 \ R3 R13 R N Z N- R5 R4 RII R1 2 N N RIO / / R6 R9 / R8 R7 R8 15 Where each of R 1, R2, R3, R4, R8, R9, R10, R 11 isCN Each of R5 and R12 is methyl or ethyl. Each of R6, R7, R13 and R14 is methyl, ethyl, alkyl, CH 2

CH

2

CO

2 H (or salts thereof), or

CH

2 CHzCO 2 R15 (where R15 is alkyl, aryl). M is In 3 11 , In 115 or a mixture of In 113 and In" 5 . 20 Z is a halide, acetate, or OH. M can also be Pd, Sn, Pt, Al, Zn, Ru, Ga.

WO 00/00204 PCT/US98/13601 50 Another family of compounds has the structure: O R8 R7 \' OR N ZN R26 O 'M R6 N N R5- N/ R3 O R4 5 Where each of R1-R8 is H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester,

CH=CHCH

2

N(CH

3

)

2 , CH=CHCH 2

N+(CH

3

)

3 X (where X is a charge balancing ion),

C(X)

2

C(X)

3 (where X is a halogen), NR9R9, CN, OH, OR9, CHO, COCH 3 , CH(OR9)CH 3 , (CH 2 )nOH, (CH 2 )nSH, (CH 2 )nO-alkoxy, (CH 2 )nSR9, (CH2)nOR9 (where n o10 = 1, 2, 3, 4, and R9 is a functional group less than or equal to 100000 daltons),

(CH

2 )nCO 2 R9 (where R9 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n=1, 2, 3, 4), (CH 2 )nCONHR9, (CH 2 )nCON(R9) 2 , CO 2 R9, CONHR9, CONR9R9, SR9 (where R9 is a functional groups less than or equal to 100000 daltons), SO 3 H, SO 3 R9, SO 2 NHR9, 15 SON(R9) 2 , SO 3 N(R9) 3 'X (where R9 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion): M is In 1 3 , In 1 ' 15 or a mixture of In 113 and In1 5 ; Z is a halide, acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, or a functional group less than or equal to 100000 daltons, protein or biomolecule. 20 WO 00/00204 PCT/US98/13601 51 Another family of compounds has the structure: O R4 0R6 N N R5 N /3 0 R4 5 where each of R 1 and R5 is alkyl or aryl. Each of R2 and R6 is methyl or ethyl. Each of R7, R8, R3, and R4 is methyl, ethyl alkyl, CH 2

CH

2

CO

2 H (or a salt therof), or

CH

2

CH

2

CO

2 R9 (where R9 is alkyl or aryl). M is In 11 , Ini 1 5 or a mixture of In 11 3 and Init 5 10 Z is a halide. acetate, OH. M can also be Pd, Sn, Pt, Al, Zn, Ru, Ga. Yet another family of compounds has the structure: 15 R2 RO10 R3 RI R4 N Z N R9 ,M\ /Rll R8 N N / R5 R7 . - R6 R14 R12 R13 Where each of R1-R14 is H, halide, methyl, ethyl, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester,

C(X)

2

C(X)

3 (where X is a halogen), NRl5Rl5, CN, OH, OR15, CHO, COCH 3 , 20 CH(OR15)CH 3 , (CH 2 )nOH, (CH 2 )nSH, (CH,)nO-alkoxy,

(CH

2 )nSR15, (CH 2 )nOR15 (where n = 1, 2, 3, 4, and R15 is a functional groups less than or equal to 100000 daltons),

(CH

2 )nCOR15 (where R14 is H, a physiologically acceptable salt, alkyl (1-6 carbons), WO 00/00204 PCT/US98/13601 52 aryl, substituted aryl. alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl and n= 1, 2, 3, 4), (CH 2 )nCONHR15, (CH,)nCON(R 15) 2 , CO 2 R15, CONHR15, CONR15R15, SR15 (where R15 is a functional group less than or equal to 100000 daltons and n=l 1, 2, 3, 4),

SO

3 H, S0 3 R15, SONHR15, SOzN(R15) 2 , SO 3 N(RI5) 3 + X - (where R15 is a functional 5 group less than or equal to 100000 daltons and X is a charge balancing ion); M is In' 13, In' 15 or a mixture of In' 13 and In 1 5 Z is a halide, acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, or a functional group less than or equal to 100000 daltons, protein or biomolecule. M can also be Pd, Sn, Pt, Al, Zn, Ru, Ga. 10 Another family of compounds has the structure: R2 R3 Ri R4 N Z N R8 N N S / R5 R7 R6 .-- R6 R9 15 where each of RI -R8 is ethyl or methyl R9 is CH 3 , SONH(CHCHO)nCH 3 (n=l to 1000), SOzN((CH 2 CHzO)nCH 3

)

2 (n=l to 1000); SO 2

NH(CH

2 )nOH (n=l to 1000), CH 3 , SO 2

N((CH

2

CH

2 )nOH) 2 (n=l to 1000);

SO

2

NC((N(CH)

2 ) ; SO 2

NH(CH

2 ) N(CH 3

)

2 (n=1 to 1000); SO 2

NH(CH

2 )nSH (n=l to 1000); SO,NHC(CH 2

CH

2

OH)

3 ; SO 2

NHCH

2 COH (or salts thereof); 20 SO 2

NH(CH

2 )nCH(NH2)CO 2 H (or salts thereof) (n=l to 5); SO 2

NHCH

2

CO

2 RIO (RIO is alkyl, aryl); SO 2

NH(CH

2 )nCH(NH 2

)CO

2 R10 (RIO is alkyl, aryl) (n=l to 5) M is InI 11, In 1 5 or a mixture of In' 13 and In 15 Z is a halide , acetate, OH. M can also be Pd, Sn, Pt, Al, Zn, Ru, Ga. 25 WO 00/00204 PCT/US98/13601 53 Another family of compounds has the structure: R2 R3 RI R4 N Z N \ /, R8 N N \~ / R5 R7 . - R6 R where each of R1-R8 is ethyl or methyl. o10 R9 is; CH 2

CO

2

NH(CH

2 CHO)nCH 3 (n=l to 1000), CH 2

CO

2

,N((CH

2

CH

2 ,O)nCH 3

)

2 ,, (n=1 to 1000): CHCONH(CH 2 )nOH (n=1 to 1000), CH 2

CO

2

,N((CH

2

CH

2 ,,)nOH) 2 ,, (n=l to 1000);

CH

2 CONC((N(CH3)2) ; CH 2

,,CO

2

NH(CH

2 )nN(CH 3

)

2 (n=1 to 1000);

CH

2

CO

2

NH(CH

2 ,,)nSH (n=1 to 1000); CH 2

CO.,NHC(CH

2

CH,OH)

3 ; CHCONHCH2COH (or salts thereof); CH 2

CO

2

,NH(CH

2

).CH(NH,)CO

2 H (or salts 15 thereof) (n=l to 5); CH 2

CO

2

NHCH

2

CO

2 R1O (R10 is alkyl or aryl);

CH

2

CO

2

NH(CH

2 )nCH(NH 2

)CO

2 R10 (R10 is alkyl, aryl) (n=1 to 5) M is In 13, In 1 5 or a mixture of In 113 and In" 11 5 Z is a halide , acetate, OH. M can also be Pd, Sn, Pt, Al, Zn, Ru, Ga. 20 Another family has the structure: R3 R4 N M N N\ /M\ /N NMN R-\ R6 N R8 R7 where each of R1-R8 is H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, C(X) 2

C(X)

3 (where X is a halogen), NR9R9, CN, OH, OR9, CHO, COCH 3 , (CH 2 )nOH, (CH 2 )nSH, 25 CH(OR9)CH 3 , (CH 2 )nO-alkoxy, (CH 2 )nSR9, (CH,)nOR9 (where n = 1, 2, 3, 4, and R9 is a functional group less than or equal to 100000 daltons), (CH 2 )nCO 2 ,R9 (where R9 is H, a WO 00/00204 PCT/US98/13601 54 physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl or substituted alkynyl, and n=l, 2, 3, 4), (CH 2 )nCONHR9,

(CH

2 )nCON(R9)2, CO2R9, CONHR9, CONR9R9, SR9 (where R9 is a functional groups less than or equal to 100000 daltons), SO 3 H, SO 3 R9, SO 2 NHR9, SO 2 N(R9) 2 , 5 SO 2 N(R9) 3

X

- (where R9 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion); M is In 13, In 15 or a mixture of In 113 and In' 115 ; Z is a halide, acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkyinyl, protein or biomolecule or functional group less than or equal to 100000 daltons. M can also be Pd, Sn, Pt, Al, Zn, Ru, Ga. 10 Another family of compounds has the structure: R3 R4 R5 R6 R2B/Czz D / \ A- BNCR R2-B iN /

B\C'R

7 A N NDN R N .Z - R8 N NM ,N R17 N N R9 D IA is N

RI

6 -CSA B-RIO 'B A ,Dzc' I15 R14 R13 11 where each of Rl-R17 is H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, 15 alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, C(X) 2

C(X)

3 (where X is a halogen), NR18R18, CN, OH, OR18, CHO, COCH 3 , (CH 2 )nOH, (CH,)nSH, CH(OR18)CH 3 , (CH 2 )nO-alkoxy, (CH,)nSR18, (CH,)nORl8(where n = 1, 2, 3, 4, and R5 is a functional group less than or equal to 100000 daltons), (CH2)nCOaR18 (where R18 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, 20 substituted alkenyl, alkynyl, or substituted alkynyl, and n=1, 2, 3, 4), (CH2)nCONHR18,

(CH

2 )nCON(R18) 2 , CO2R18, CONHR18, CONR18RI8, SR18 (where R18 is a functional groups less than or equal to 100000 daltons), SO 3 X, SO 3 R18, SO2NHR18, SO 2 N(R18) 2 ,

SO

2 N(R18) 3

+X

- (where R18 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion); M is In 13 , In 115 or a mixture of In 113 and In 15; Z is a halide, 25 acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyil, protein or biomolecule or functional group less than or equal to 100000 daltons. M can also be Pd, or Ga.

WO 00/00204 PCT/US98/13601 55 Still another family has the structure: R4 R5 R8 R9 R3-B / 710 A EF-- D\ AM / \ N I R4 FN M"\ E.N R2 \ .N. N[ R12 N M N N N\ N N R13 R23 E- E / N R14 D A\ R22-C RI9 RI8 B-R15 BI A\ /D C I R20 RI7 R16 R21 5 where each of Rl-R24 is H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl. substituted alkenyl, alkynyl. substituted alkynyl, amide, ester. C(X) 2 C(X)3 (where X is a halogen), NR25R25, CN, OH, OR25, CHO, COCH 3 , (CH2)nOH, (CH2)nSH, CH(OR25)CH 3 , (CH 2 )nO-alkoxy, (CH 2 )nSR25, (CH 2 )nOR25 (where n = 1, 2, 3, 4, and R25 is a functional groups less than or equal to 100000 daltons), (CH 2 )nCO 2 R25 (where 10 R25 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n= 1, 2, 3, 4),

(CH

2 )nCONHR25, (CH 2 )nCON(R25) 2 , CO2R25, CONHR25, CONR25R25, SR25 (where R25 is a functional group less than or equal to 100000 daltons), SO 3 H, SO 3 R25, SO2NHR25. SO 2 N(R25) 2 , SO 2 N(R25)3' X - (where R25 is a functional group less than or 15 equal to 100000 daltons and X is a charge balancing ion); M is In" 113 , Ini 1 5 or a mixture of In' l3 and In" 5 ; A, B, C, D, E, F are; C, N, O+, O, S, Te, P, N'(R25)X (where R25 is a functional groups less than or equal to 100000 daltons and X is a charge balancing ion), or combinations thereof; Z is a halide , acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, protein or biomolecule or functional 20 group less than or equal to 100000 daltons. M can also be Pd or Ga.

WO 00/00204 PCT/US98/13601 56 Another family of compounds has the structure: RI R5 \ I~ N R3 M N N H R4 X R2 5 where each of Rl- R5 is CH 2

CH

3 , CH=CH 2 , CH=CHCH 2

N(CH

3 )2 CH=CHCH 2 N(CH3)3 X- (where X is a charge balancing ion), C(X) 2

C(X)

3 (where X is a halogen), CHO,

COCH

3 , CO2H, CO2R6, CONHR7, CH=CHCHO,

CH

2 Y, (where Y = H, halogen, OH, OR6 or is a functional group less than or equal to 100000 daltons), CH=CHCH 2 OH,

CH=CHCH

2 OR6, CH(OH)CH 3 , CH(OR6)CH 3 , H, halide, alkyl, cyclic alkyl (1-6 10 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, NR6R6, CN, OH, OR6, (CH 2 ).OH, (CH 2 ).SH, (CH,)nO-alkoxy,

(CH

2 )nSR6, (CH2)nOR6 (where n = 1, 2, 3, 4, and R6 is a functional group less than or equal to 100000 daltons), (CH,)nCOR6 (where R6 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted 15 alkynyl, and n=l, 2, 3, 4), (CH 2 )nCONHR6,

(CH

2 )nCON(R6)2, CO2R6, CONHR6, CONR6R6, SR6 (where R6 is a functional group less than or equal to 100000 daltons),

SO

3 H, SO 3 R6, SO2NHR6, SO 2 N(R6) 2 , SO 2 N(R6)3 +X - (where R6 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion); X is . O, 2H, (H, OH), S, (H, OR6) or a ketone protecting group; M is In 3 In '5 or a mixture of In'' 3 and In' 5 ; Z 20 is a halide , acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkyinyl, protein or biomolecule or functional group less than or equal to 100000 daltons. M can also be Pd, Sn, Pt, Al, Zn, Ru, Ga. 25 WO 00/00204 PCT/US98/13601 57 Still another family of compounds has the structure: RI R5 z R3 M N N H H R4 X R2 wherein: 5 R1 is CH=CH 2 , CHO, Et, COCH 3 R2 is CO 2

CH

3 ,CO2H, amide R3 and R4 are H R5 is CH 3 XisO 10 Mis In 1 1 3 In 1 5 or a mixture of Ini1 3 and In"l 5 Z is a halide, acetate or OH. M can also be Ag, Al, Ce, Co, Cr, Cu, Dy, Er, Fe, Ga, Hf, Ho, La, Lu, Mo, Nd, Pb, Pd, Pr, Pt, Rh, Sb, Sc, Sm, Sn, Pt, Ru, Tb, Th, Ti, TI, Tm, U, V, Y, Yb, Zn or Zr, preferably Pd, Sn, Pt, Al, Zn, Ru, Ga. 15 Another family of compounds has the structure: RI R5 NzN 20 3 M H N N H R4 R6 25 R2 where each of R1- R6 is; CH 2

CH

3 , CH=CH 2 , CH=CHCH 2 N(CH3)2, CH=CHCH 2

N+(CH

3

)

3 X (where X is a charge balancing ion), C(X) 2

C(X)

3 (where X is a halogen), CHO,

COCH

3 , CO 2 H, CO2R7, CONHR7, CH=CHCHO, CH 2 Y, (where Y = H, halogen, OH, 30 OR7 or is a functional group less than or equal to 100000 daltons), CH=CHCH 2

OH,

WO 00/00204 PCT/US98/13601 58

CH=CHCH

2 OR7, CH(OH)CH 3 , CH(OR7)CH 3 , H, halide, alkyl, cyclic alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, NR7R7, CN, OH, OR7, (CH 2 )nOH, (CH 2 )nSH, (CH2)nO-alkoxy, (CH 2 )nSR7, (CH,)nOR7 (where n = 1, 2, 3, 4, and R7 is a functional group less than or equal to 100000 5 daltons), (CHz)nCO 2 R7 (where R7 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n=l, 2, 3, 4), (CH,)nCONHR7, (CH2)nCON(R7) 2 , CO2R7, CONHR7, CONR7R7, SR7 (where R7 is a functional group less than or equal to 100000 daltons),

SO

3 H, SO 3 R7, SO 2 NHR7, SO 2 N(R7) 2 , SO 2 N(R7) 3

+X

- (where R7 is a functional group less 10 than or equal to 100000 daltons and X is a charge balancing ion); M is In" 3 , In' 5 or a mixture of In" 3 and In' 15 ; Z is a halide, acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl. alkynyl, substituted alkynyl, protein or biomolecule or functional group less than or equal to 100000 daltons; with the proviso that when R2 = COzNHR6, R6 can not be a mono- or di-carboxylic acid of an amino acid. 15 M can also be Ag, Al, Ce, Co, Cr, Cu, Dy, Er, Fe, Ga, Hf, Ho, La, Lu, Mo, Nd, Pb, Pd, Pr, Pt, Rh, Sb, Sc, Sm, Tb, Th, Ti, TI, Tm, U, V, Y, Yb, Zr, preferably .Pd, Pt. Ga, Al, Ru, Sn or Zn. Another family of compounds has the following structure: 20 RI R5 25 N N H H R4 R6 R2 30 where each of RI- R6 is; CH 2

CH

3 , CH=CH 2 , CH=CHCH 2 N(CH3)2, CH=CHCH 2

N+(CH

3

)

3 X (where X is a charge balancing ion), C(X) 2

C(X)

3 (where X is a halogen), CHO,

COCH

3 , CO 2 H, CO 2 R7, CONHR7, CH=CHCHO, CH 2 Y, (where Y = H, halogen, OH, OR7 or is a functional group less than or equal to 100000 daltons), CH=CHCH 2 OH, 35 CH=CHCH 2 OR7, CH(OH)CH 3 , CH(OR7)CH 3 , H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, NR7R7, CN, OH, OR7, (CH 2 )nOH, (CH 2 )nSH, (CH 2 )nO-alkoxy, (CH 2 )nSR7, WO 00/00204 PCT/US98/13601 59

(CH

2 )nOR7 (where n = 1, 2, 3, 4, and R7 is a functional group less than or equal to 100000 daltons), (CH,)nCO 2 R7 (where R7 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl or substituted alkynyl, and n= 1, 2, 3, 4), (CH,)nCONHR7, (CH,)nCON(R7)2, C0 2 R7, CONHR7, CONR7R7, SR7 5 (where R7 is a functional group less than or equal to 100000 daltons),

SO

3 H, SO 3 R7,

SO

2 NHR7, SO 2 N(R7) 2 , SO-N(R7) 3 X - (where R7 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion); M is In" 13 , In"' or a mixture of In" 113 and In' 115 ; Z is a halide , acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, protein or biomolecule or functional group less than o10 or equal to 100000 daltons. Still another family of compounds has the following structure: RI R5 N zN N, I / R3\ M\ H N N H R4 R6 R2 15 wherein; R 1 is CH=CH 2 , CHO, Et, COCH 3 R2 is CO 2

CH

3 R3 is H R4 is CH 2

CO

2

CH

3 , CO 2 CH3, CH 2

CO

2 H (or a salt thereof),

CO

2 H (or a salt thereof). 20 R5 is CH 3 R6 is CO 2 H, CO 2 Me or an amide M is In 1 3 , In'' 5 or a mixture of In 1 3 and In" 115 Z is a halide, acetate, or OH. M can also be Ag, Al, Ce, Co, Cr, Cu, Dy, Er, Fe, Ga, Hf, Ho, In, La, Lu, Mo, Nd, Pb, Pd, 25 Pr, Pt, Rh, Sb, Sc, Sm. Sn, Tb, Th, Ti, TI, Tm, U, V, Y, Yb, Zn, or Zr, preferably Pd, Pt, Ga, Al, Ru, Sn or Zn.

WO 00/00204 PCT/US98/13601 60 Another family of compounds has the structure: RI R2 R5 R4 R3 R6 N N R7 /M R13 N N R8 I R12 R9 RIO RIl where each Rl-R13 is H, halide, alkyl, vinyl, cyclic alkyl (3-6 carbons), aryl, substituted 5 aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, CH=CHCH2 N(CH3)2 , CH=CHCH 2 N-(CH3)3 X (where X is a charge balancing ion),

C(X)

2

C(X)

3 (where X is a halogen), NR14R14, CN, OH, OR14, CHO, COCH 3 , (CH,)nOH,

(CH

2 )nSH,

(CH

2 )nO-alkoxy, CH(OH)CH3, CH(OR14)CH3

(CH

2 )nSR14,

(CH

2 )nOR 14 (where n = 1, 2, 3, 4, and R14 is a functional group less than or equal to 10 100000 daltons), (CH2)nCO 2 R14 (where R14 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n=l, 2, 3, 4), (CH,)nCONHR14, (CH2)nCON(R1 4 )2, CO 2 R14, CONHR14, CONR14R14. SR14 (where R14 is a functional group less than or equal to 100000 daltons),

SO

3 X. SO 3 R14, SO 2 R14, SO 2 NHR14,

SO

2 N(R14)2,

SO

2 N(R14) 3 'X (where R14 15 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion); M is In" 3 , In"5 or a mixture of In13 and In" 5 ; Z is a halide, acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, suibstituted alkynyl, protein or biomolecule or functional group less than or equal to 100000 daltons.

WO 00/00204 PCT/US98/13601 61 Still another family of compounds has the following structure: RI R2 R5 R4 R3 R6 ' N Z N R7" M / RI3 N N R8" / RI2 R9 RIO RII where each of RI and R2 is CO 2 R14 (where R14 is alkyl or aryl), CO 2 H (or a salt therof), 5 SOPh, or CN; R3, R6, R8, and R12 are Me. R5 is CH=CH 2 , or CH(OR14)CH3 (where R14 is alkyl or aryl) R4, R7, R13, RIO are H R9, R 11 are CH 2

CH

2

CO

2 R15 (where R15 is alkyl or H or a salt of the carboxylic acid) 10 M is In l 3, In 115 or a mixture of In' 3 and In 5 ; Z is a halide, acetate, OH. M can also be Ag, Al, Ce, Co, Cr, Cu, Dy, Er, Fe, Ga, Hf, Ho, La, Lu, Mo, Nd, Pb, Pd, Pr, Pt, Rh, Sb, Sc, Sm, Tb, Th, Ti, TI, Tmin, U, V, Y, Yb or Zr, preferably Pd, Pt, Ga, Al, Ru, Sn or Zn. 15 Still another family of compounds has the following structure: RI1 R5 R6 R7 N Z N R3 M / H N N H R2 R4 X R2 20 where each of Rl- R7 is CH2CH 3 , CH=CH 2 , CH=CHCH 2 N(CH3)2, CH=CHCHN+(CH3)3 X- (where X is a charge balancing ion), C(X) 2 C(X)3 (where X is a halogen),

CHO,

WO 00/00204 PCT/US98/13601 62 OR8 or is a functional group less than or equal to 100000 daltons),

CH

2

CO

2 R8, CHCONHR8, CH=CHCH 2 OH, CH=CHCH2OR8, CH(OH)CH3, CH(OR8)CH3, H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, NR8R8, CN, OH, OR8, CHO,

(CH

2 )nOH, 5 (CH,)nSH, (CH,)nO-alkoxy, (CH,)SR8. (CH2)nOR8 (where n = 1, 2, 3, 4, and R8 is a functional group less than or equal to 100000 daltons), (CHs)nCOR8 (where R8 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n=l, 2, 3, 4), (CH 2 )nCONHR8, (CH,)nCON(R8)2,

CO

2 R8, CONHR8, CONR8R8, SR8 (where R8 is a functional group 10 less than or equal to 100000 daltons),

SO

3 H, SO 3 R8, SO 2 NHR8,

SO

2 N(R8)2, S0o 2 N(R8) 3 X (where R8 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion), protein or biomolecule or functional group less than or equal to 100000 daltons; X is 0, H2, (H, OH), S, (H, OR8) or a ketone protecting group; M is In' 1 3, In 115 or a mixture of In 1 13 and In'1 5 ; Z is a halide , acetate, OH, alkyl, aryl, 15 substituted aryl, atlkenyl, substituted alkenyl, alkynyl, substituted alkynyl, protein or biomolecule or functional group less than or equal to 100000 daltons. M can also be Ag, Al, Ce, Co, Cr, Cu, Dy, Er, Fe, Ga, Hf, Ho, La, Lu, Mo, Nd, Pb, Pd, Pr, Pt, Rh, Sb, Sc, Sm, Tb, Th, Ti, TI, Tm, U, V, Y, Yb or Zr, preferably Pd, Pt, Ga, Al or Ru. 20 Still another family of compounds has the following structure: R I R5 R6 R7 N ,N R3 M / H N N H R4 X R2 wherein; RI = COCH3 R3 and R5 = H, CH 3 R7 = H or OH 25 R6 = Me or OH R4 = H or CO 2 CH3 WO 00/00204 PCT/US98/136 0 1 63 R2 = CO2R8 (where R8 is alkyl) Mis In 113 " , In"' or a mixture of In' and In 5 Z is a halide, acetate, or OH. X=O 5 M can also be Ag, Al, Ce, Co, Cr, Cu, Dy, Er, Fe, Ga, Hf, Ho, La, Lu, Mo, Nd, Pb, Pd, Pr, Pt, Rh, Sb, Sc, Sm, Tb, Th, Ti, T1, Tm, U, V, Y, Yb or Zr, preferably Pd, Pt, Ga, Al or Ru. Another family of compounds has the structure: R3 R4 R2 RI 3 R 3 R5 \ R6 , / R12 A D R7 \ / Rl R8 R9 RIO t werein each of RI1-R13 is H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, CH=CHCH2 N(CH3)2 , CH=CHCH 2 N'(CH3)3 X- (where X is a charge balancing ion),

C(X)

2 C(X)3 (where X is a halogen), NRI4RI4, CN, OH, OR 14, CHO,

(CH

2 )nOH, 15 (CH,)nSH, (CH,)nO-alkoxy, CH(OH)CH3, CH(OR14)CH3

(CH

2 )nSR14,

(CH

2 )nOR14 (where n = 1, 2, 3, 4, and R14 is a functional group less than or equal to 100000 daltons),

(CH

2 )nCO,Rl14 (where R14 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl or substituted alkynyl, and n= 1, 2, 3, 4), (CH,)nCONHR I 4 , (CH')nCON(R1 4 )2, CO 2 R14, CONHRI4, CONR14R14, SR14 20 (where R14 is a functional group less than or equal to 100000 daltons),

SO

3 H, SO 3 R14, SO,NHR14,

SO

2 N(R14)2,

SO

2 -N(RI4) 3

+

X (where R14 is a functional group less than or equal to 2000 daltons and X is a charge balancing ion); A, B, C, D are; C, N, h, , S, Te, P or combinations thereof; M is In 3 , In' 5 or a mixture of In t and In" 5 ; Z is a halide, acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted 25 alkynyl, protein or biomolecule or functional group less than or equal to 100000 daltons. M can also be Ag, Al, Ce, Co, Cr, Cu, Dy, Er, Fe, Ga, Hf, Ho, In, La, Lu, Mo, Mg, Nd, Pb, Pd, Pr, Pt, Rh, Sb, Sc, Sn, Sm, Tb, Th, Ti, TI, Tin, U, V, Y, Yb, Zn, Zr.

WO 00/00204 PCT/US98/136 0 1 64 Still another family of compounds has the following structure: R3 RI R4 R2 R13 R5 B ZN R6-A ,M, C-R12 N N R \ k R1 D* R8 R9 RIO were each of RI-R13 is H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, 5 alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, CH=CHCH2 N(CH3)2 , CH=CHCH 2 N+(CH3)3 X (where X is a charge balancing ion), CH=CHCHC, H, R1N(COH3)2,OH

C(X)

2

C(X)

3 (where X is a halogen), NR4R14, CN, OH, R4, O, (CH)OH, (CH )nSH, (CH,)nO-alkoxy, CH(OH)CH3, CH(OR14)CH 3 , (CH)nSR14,

(CH

2 )nOR14 (where n = 1, 2, 3, 4, and R14 is a functional group less than or equal to 100000 daltons), 10

(CH

2 )n COR14 (where R14 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n=1, 2, 3, 4), (CHa,)CONH R 14 n (CH,)nCON(R1 4 )2, CO 2 R14, CONHR14, CONR14RI 4 , SR14 (where R14 is a functional group less than or equal to 100000 daltons),

SO

3 H, SO 3 R14, SONHR14, SOzN(RI4)2,

SO

2 N(R14) 3 X - (where R14 is a functional group less than or 15 equal to 100000 daltons and X is a charge balancing ion); A, B, C, D are; C, N, 0

+

, 0, S, Te, P or combinations thereof; M is In 1 1 3, in 15 or a mixture of In' 13 and In1 5 ; Z is a halide, acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, protein or biomolecule or functional group less than or equal to 100000 daltons. 20 M can also be Ag, Al, Ce, Co, Cr, Cu, Dy, Er, Fe, Ga, Hf, Ho, La, Lu, Mo, Mg, Nd, Pb, Pd, Pr, Pt, Rh, Sb, Sc, Sn, Sm, Tb, Th, Ti, TI, Tm, U, V, Y, Yb, Zn or Zr.

WO 00/00204 PCT/US98/13601 65 Another family of compounds has the following structure: R2 RI R5 R4 R3 R6 \ R7 \ M / R13 N N R \ / R12 R9 RIO Rll were each of RI-R13 is H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, 5 alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, CH=CHCH 2 N(CH3)2 , CH=CHCH2 N(CH3)3 X- (where X is a charge balancing ion), CHCHHN(H)2,CH=C H ( 3)

C(X)

2

C(X)

3 (where X is a halogen), NR14R14, CN, OH, OR14, CHO, (CH,)nOH, (CHz)nSH, (CH2)nO-alkoxy , CH(OH)CH3, CH(OR14)CH 3 (CH,)nSR14,

(CH

2 )nOR14 (where n = 1, 2, 3, 4, and R14 is a functional group less than or equal to 100000 daltons), 10 (CH,)nCOzR14 (where R14 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n=l, 2, 3, 4), (CH 2 )nCONHR1 4 , (CH 2 )nCONH(R1 4 )2, CO2R14, CONHR14, CONR14R14, SR14 (where R14 is a functional group less than or equal to 100000 daltons),

SO

3 H,

SO

3 R14, SO 2 NHR14,

SO

2 N(R14)2,

SO

2 N(R14) 3 X - (where R14 is a functional group less 15 than or equal to 100000 daltons and X is a charge balancing ion); M is In. 1 3 . In1 5 or a mixture of In" 1 3 and In' 5 ; Z is a halide, acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, protein or biomolecule or functional group less than or equal to 100000 daltons. M can also be Ag, Al, Ce, Co, Cr, Cu, Dy, Er, Fe, Ga, Hf, Ho, In, La, Lu, Mo, Mg, Nd, Pb, 20 Pd, Pr, Pt, Rh, Sb, Sc, Sn, Sm, Tb, Th, Ti, TI, Tm, U, V, Y, Yb, Zn or Zr.

WO 00/00204 PCT/US98/13601 66 Another family of compounds has the following structure: R2 RI R5 R4 R3 R6 R6\N Z N R7 . M / R13 N N R \ ,, /R12 R9 RIO Rll Where each of RI and R2 is CO 2 R14 (where R14 is alkyl or aryl), CO 2 H (or a salt 5 thereof),

SO

2 Ph, CN or a combination thereof; Each of R3, R6, R8, R12 is Me. R5 is CH=CH2 , or CH(OR14)CH3 (where R14 is alkyl or aryl) Each of R4, R7, R13, RIO is H R9 and R 11 are CH 2

CH

2 CO2R15 (where R15 is alkyl or H or a salt of the carboxylic I0 acid). M is In" , In5 or a mixture of In' 13 and In' 15 Z is a halide , acetate, or OH. M can also be Ag, Al, Ce, Co, Cr, Cu, Dy, Er, Fe, Ga, Hf, Ho, In, La, Lu, Mo, Mg, Nd, Pb, Pd, Pr, Pt, Rh, Sb, Sc, Sm, Sn, Tb, Th, Ti, TI, Tm, U, V, Y, Yb, Zn or Zr, preferably Pd, 15 Pt, Ga, Al, Ru, Sn or Zn. Another family of compounds has the following structure: R2 R7

R

6

R

4 RI R5 R8 N NZ N R9 M RI5 N N RIO \ / R14 Rll RI2 RI3 where each of RI-R15 is H, halide, alkyl, vinyl, cyclic alkyl (3-6 carbons), aryl, 20 substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, CH=CHCH 2 N(CH3)2 , CH=CHCH2 N+(CH3)3 X (where X is a charge balancing ion), WO 00/00204 PCT/US98/13601 67

C(X)

2 C(X)3 (where X is a halogen), NR16R16, CN, OH, OR16, CHO, COCH 3 ,

(CH

2 )nOH,

(CH

2 )nSH,

(CH

2 )nO-alkoxy ,

SO

2 Ph, CH(OH)CH3, CH(ORI4)CH 3 (CH,)nSR16,

(CH

2 )nOR1 6 (where n = 1, 2, 3, 4, and R16 is a functional group less than or equal to 100000 daltons), (CH,)nCO 2 R1 6 (where R16 is H, a physiologically acceptable 5 salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl or substituted alkynyl, and n=l, 2, 3, 4), (CH 2 )nCONHR1 6 , (CH 2 )nCON(R1 6 )2, CO2R16, CONHR16, CONR16R1 6 , SR16 (where R16 is a functional group less than or equal to 100000 daltons),

SO

3 X, SO 3 R16, SO2NHR16,

SO

2 N(R16)2,

SO

2

N(R

1 6) 3 +X - (where R16 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion); 10 M is In" 13 , In 15 or a mixture of In13 and In" 15 ; Z is a halide , acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, protein or biomolecule or functional group less than or equal to 100000 daltons. M can also be Ag, Al, Ce, Co, Cr, Cu, Dy, Er, Fe, Ga, Hf, Ho, In, La, Lu, Mo, Mg, Nd, Pb, Pd, Pr, Pt, Rh, Sb, Sc, Sm, Sn, Tb, Th, Ti, TI, Tm, U, V, Y, Yb, Zn or Zr, preferably Pd, 15 Pt, Ga, Al, Ru, Sn or Zn. Another family of compounds has the following structure: R2 R7

R

6

R

4 RI R5 R8 'N Z/N R9 M / R15 N N RIO \ / R14 Rll RI2 RI3 where each of R1, R2, R3 and R4 is CO 2 R16 (where R16 is alkyl or aryl),

CO

2 H (or a salt 20 thereof) or SOzPh, CN: Each of R5, R8, RO10 and R14 is Me. R7 is CH=CH, or CH(OR16)CH3 (where R16 is alkyl or aryl) Each of R6, R9, R12 and R15 is H Each of R11 and R13 is CH 2

CH

2 CO2R1 6 (where R16 is alkyl or H or a salt of the 25 carboxylic acid), or an amide M is In 3 , In' 15 or a mixture of In' 3 and In" 5 WO 00/00204 PCT/US98/13601 68 Z is a halide , acetate, or OH. M can also be Ag, Al, Ce, Co, Cr, Cu, Dy, Er, Fe, Ga, Hf, Ho, La, Lu, Mo, Mg, Nd. Pb, Pd, Pr. Pt. Rh. Sb, Sc, Sm, Tb, Th, Ti. T1. Tm. U, V, Y. Yb or Zr, preferably Pd. Pt, Ga, Al. Ru. Sn or Zn. 5 Still another family of compounds has the following structure: R2 RI R5 R 4 R3 \ \. R3B B, R6- IN R7-A M C-R13 R D R12 D R9 RIO Rll Where each of R1-R13 is H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, o10 alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, CH=CHCH 2 N(CH3)2 , CH=CHCH 2 N+(CH3)3 X (where X is a charge balancing ion),

C(X)

2 C(X)3 (where X is a halogen), NR14R14, CN, OH, OR14, CHO,

(CH

2 )nOH,

(CH

2 )nSH, (CH,)nO-alkoxy, CH(OH)CH3, CH(OR14)CH 3 (CH2)nSR14,

(CH

2 )nOR14 (where n = 1, 2, 3, 4, and R14 is a functional group less than or equal to 100000 daltons), 15 (CH,)nCO 2 RI4 (where R14 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n= 1, 2, 3, 4), (CH 2 )nCONHR14, (CH,)nCON(R1 4 )2, CO2R14, CONHR14, CONR14R14. SR14 (where R14 is a functional group less than or equal to 100000 daltons), SO3H,

SO

3 R14.

SO

2 NHR14,

SO

2 N(R14)2,

SO

2 N(R14) 3 +X - (where R14 is a functional group less than or 20 equal to 100000 daltons and X is a charge balancing ion); A, B, C, D are; C, N, 0

+

, O, S, Te, P or combinations thereof; M is In 3 , In 11 5 or a mixture of In1 13 and In" 5 ; Z is a halide , acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, protein or biomolecule or functional group less than or equal to 100000 daltons. 25 M can also be Ag, Al, Ce, Co, Cr, Cu, Dy, Er, Fe, Ga, Hf, Ho, In, La, Lu, Mo, Mg, Nd, Pb, Pd, Pr, Pt, Rh, Sb, Sc, Sm, Sn, Tb, Th, Ti, TI, Tm, U, V, Y, Yb, Zn or Zr, preferably Pd, Pt, Ga, Al, Ru, Sn or Zn.

WO 00/00204 PCT/US98/13601 69 Another family of compounds has the structure: R3 R11 R4 R2 R5 RIO-A M C-R12 N' N RI \ R6 R9 I R7 R14 R13 R8 Where each of R1-R14 is H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, 5 CH=CHCH2 N(CH3)2 , CH=CHCH2 N*(CH3)3 X (where X is a charge balancing ion),

C(X)

2

C(X)

3 (where X is a halogen), NR15R15, CN, OH, OR15, CHO, (CH,)nOH, (CH,)nSH,

(CH

2 )nO-alkoxy, CH(OH)CH3, CH(OR15)CH3

(CH

2 )nSR15,

(CH

2 )nOR15 (where n = 1, 2, 3, 4, and R15 is a functional group less than or equal to 100000 daltons),

(CH

2 ) nCOzR15 (where R15 is H, a physiologically acceptable salt, alkyl (1-6 carbons), 10 aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n=1, 2, 3, 4), (CH 2 )nCONHR1 5 , (CH2)nCON(R15)2,

CO

2 R15, CONHR15, CONR15R15, SR15 (where R15 is a functional group less than or equal to 100000 daltons),

SO

3 H, SO 3 R15,

SO

2 NHR15,

SO

2 N(R15)2,

SO

2 N(R15)3X- (where R15 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion); A, B, C, D are; C, N, 0

+

, O, S, 15 Te, P or combinations thereof; M is In 1 13 , In15 or a mixture of In 1

"

3 and In 11 5 ; Z is a halide , acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, protein or biomolecule or functional group less than or equal to 100000 daltons. M can also be Ag, Al, Ce, Co, Cr, Cu, Dy, Er, Fe, Ga, Hf, Ho, La, Lu, Mo, Mg, Nd, Pb, 20 Pd, Pr, Pt, Rh, Sb, Sc, Sm, Sn, Tb, Th, Ti, TI, Tmin, U, V, Y, Yb, Zn or Zr.

WO 00/00204 PCT/US98/13601 70 Another family of compounds has the following structure: RI R4 R3 , M H N N ' H j H A X B R2 5 Where each of R1-R4 is CH2CH3, CH=CH2 , CH=CHCHN(CH3)2, CH=CHCH2 N'(CH3)3 X (where X is a charge balancing ion), C(X) 2 C(X)3 (where X is a halogen), CHO,

COCH

3 , CO 2 H, CO2R5, CONHR5, CH=CHCHO,

CH

2 Y, (where Y = H, halogen, OH, OR5 or is a functional group less than or equal to 100000 daltons),

CH

2

CO

2 R5,

CH

2 CONHR5, CH=CHCH20H, CH=CHCH 2 OR5, CH(OH)CH3, CH(OR5)CH3, H, 10 halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, NR5R5, CN, OH, OR5, CHO,

(CH

2 )nOH, (CH2)nSH, (CH,)nO-alkoxy,

(CH

2 )nSR5,

(CH

2 )nOR5 (where n = 1, 2, 3, 4, and R5 is a functional group less than or equal to 100000 daltons),

(CH

2 )nCO 2 R5 (where R5 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, 15 substituted alkenyl, alkynyl, or substituted alkynyl, and n=l1, 2, 3, 4), (CH 2 )nCONHR5, (CH,)nCON(R5)2 , CO 2 R5, CONHR5, CONR5R5, SR5 (where R5 is a functional group less than or equal to 100000 daltons),

SO

3 H, SO 3 R5, SO 2 NHR5,

SO

2 N(R5)2,

SO

2 N(R5) 3 *X (where R5 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion), protein or biomolecules or functional groups less than or equal 20 to 100000 daltons; A and B are O, NH, NR5 or combinations thereof; X is , O, NR5 (where R5 is H, alkyl (1-10 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynylk, substituted alkynyl, an amino acid, an amino acid ester or a functional group less than or equal to 100000 daltons); M is In 1 3 , In"' or a mixture of In 13 and In1 5 ; Z is a halide , acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, 25 substituted alkynyl, protein or biomolecule or functional group less than or equal to 100000 daltons.

WO 00/00204 PCT/US98/13601 71 M can also be Ag, Al, Ce, Co, Cr, Cu, Dy, Er, Fe, Ga, Hf, Ho, La, Lu, Mo, Mg, Nd, Pb, Pd, Pr, Pt, Rh, Sb, Sc, Sm, Tb, Th, Ti, TI, Tm, U, V, Y, Yb or Zr, preferably Pd, Pt, Ga, Al, Ru, Sn or Zn. 5 Another family of compounds has the following structure: RI R5 R 6 \ R7 \ NZ N R3 ,M / H N N H H R8 R4 R2 Where each of R I- R8 is CH 2

CH

3 , CH=CH 2 , CH=CHCH 2

N(CH

3 )2, CH=CHCH 2

N+(CH

3

)

3 X (where X is a charge balancing ion), C(X) 2

C(X)

3 (where X is a halogen), CHO, 10 COCH 3 , CO 2 H, CO 2 R9, CONHR9, CH=CHCHO, CH 2 Y, (where Y = H, halogen, OH, OR9 or is a functional group less than or equal to 100000 daltons), CH 2

CO

2 R9,

CH

2 CONHR9, CH=CHCH 2 OH, CH=CHCH 2 OR9, CH(OH)CH 3 , CH(OR9)CH 3 , H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, NR9R9, CN, OH, OR9, CHO, (CH 2 )nOH, 15 (CH 2 )nSH, (CH,)nO-alkoxy, (CH,)nSR9,

(CH,

2 )OR9 (where n = 1, 2, 3, 4, and R9 is a functional group less than or equal to 100000 daltons), (CH 2 ) nCO 2 R9 (where R9 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n=l, 2, 3, 4), (CH 2 )nCONHR9,

(CH

2 )nCON(R9) 2 , CO 2 R9, CONHR9, CONR9R9, SR9 (where R9 is a functional group 20 less than or equal to 100000 daltons), SO 3 H, SO 3 R9, SO 2 NHR9, SO 2 N(R9) 2 ,

SO

2 N(R9) 3

+X

- (where R9 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion), protein or biomolecule or functional group less than or equal to 100000 daltons; X is O, H 2 , (H, OH), (H, OR9), S, or a ketone protecting group; M is In 1 3 , In 115 or a mixture of In 13 and In"15 ; Z is a halide , acetate, OH, alkyl, aryl, 25 substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkyinyl, protein or biomolecule or functional group less than or equal to 100000 daltons.

WO 00/00204 PCT/US98/13601 72 M can also be Ag, Ce, Co, Cr, Cu, Dy, Er, Fe, Hf, Ho, La, Lu, Mo, Mg, Nd, Pb, Pr, Rh, Sb, Sc, Sm, Sn, Tb, Th, Ti, T1, Tm, U, V, Y, Yb or Zr, preferably Pd, Pt, Ga, Al, Ru, Sn or Zn. 5 Another family of compounds has the following structure: RI R4 R5 R6 N ZN R3 M H N N H H A X B R2 Where each of R1- R6 is CH 2

CH

3 , CH=CH 2 , CH=CHCH 2

N(CH

3

)

2 , CH=CHCH 2

N'(CH

3

)

3 X (where X is a charge balancing ion), C(X) 2

C(X)

3 (where X is a halogen), CHO, COCH 3 , 10 CO 2 H, CO2R7, CONHR7, CH=CHCHO, CH 2 Y, (where Y = H, halogen, OH, OR7 or is a functional group less than or equal to 100000 daltons), CH 2

CO

2 R7, CH 2 CONHR7,

CH=CHCH

2 OH, CH=CHCH 2 OR7, CH(OH)CH 3 , CH(OR7)CH 3 , H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, NR7R7, CN, OH, OR7, CHO, (CH 2 )nOH, (CH 2 )nSH, (CH,)nO 15 alkoxy, (CH,)nSR7, (CH,)nOR7 (where n = 1, 2, 3, 4, and R7 is a functional group less than or equal to 100000 daltons), (CH 2 )nCOzR7 (where R7 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n= 1, 2, 3, 4), (CH 2 )nCONHR7, (CH 2 )nCON(R7) 2 ,

CO

2 R7, CONHR7, CONR7R7, SR7 (where R7 is a functional group less than or equal to 20 100000 daltons), SO 3 H, SO 3 R7, SO 2 NHR7, SO 2 N(R7) 2 , SO 2 N(R7) 3 X - (where R7 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion), protein or biomolecule or functional group less than or equal to 100000 daltons; X is , O, NR7 (where R7 is H, alkyl (1-10 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, an amino acid, an amino acid ester or a functional 25 group less than or equal to 100000 daltons); A and B are O, NH, NR7 or combinations thereof; M is In' 13, In 1 5 or a mixture of In 113 and In 15 ; Z is a halide, acetate, OH, alkyl, WO 00/00204 PCT/US98/13601 73 thereof; M is In' 13 , In ' 5 or a mixture of In 1 13 and In' ;15 Z is a halide , acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, protein or biomolecule or functional group less than or equal to 100000 daltons. M can also be Ag, Ce, Co, Cr, Cu, Dy, Er, Fe, Hf, Ho, La, Lu, Mo, Mg, Nd, Pb, Pr, Rh, 5 Sb, Sc. Sm, Sn, Tb, Th, Ti, T1, Tm, U, V, Y, Yb or Zr, preferably Pd, Pt, Ga, Al, Ru, Sn or Zn. Another family of compounds has the following structure: RI1 R4 R5 R6 N Z N R3 M / H N N H H AX B R2 10 wherein; R 1 is CH=CH2, Et, CHO, or COCH 3 R2 is CO2CH 3 , CO 2 H, CO 2 R7 (R7 is an alkyl, phenyl), or an amide R3 is H 15 R4 is Me Each of R5 and R6 is OH Each of A and B is O or NR7 ( R7 is alkyl). X is O or NR7 (R7 is alkyl, an amino acid, an alcohol containing group, or an ether containing group) 20 M is In" 3 ,In 15 or a mixtureo f In I 3 and In

"

5 Z is a halide, acetate, or OH. M can also be Ag, Al, Ce, Co, Cr, Cu, Dy, Er, Fe, Ga, Hf, Ho, La, Lu, Mo, Mg, Nd, Pb, Pr, Rh, Sb, Sc, Sm, Tb, Th, Ti, T1, Tm, U, V, Y, Yb or Zr, preferably Pd, Pt, Ga, Al, Ru, Sn or Zn. 25 WO 00/00204 PCT/US98/13601 74 Another family of compounds has the following structure: RI R5 R6 R6 N Z IN R3 / H N N H H R2 R4 X where each of R 1- R6 is CH 2

CH

3 , CH=CH2, CH=CHCH 2

N(CH

3

)

2 , CH=CHCH 2

N+(CH

3

)

3 5 X- (where X is a charge balancing ion), C(X) 2

C(X)

3 (where X is a halogen), CHO, COCH3, CO 2 H, CO2R7, CONHR7, CH=CHCHO, CH 2 Y, (where Y = H, halogen, OH, OR7 or is a functional group less than or equal to 100000 daltons), CH 2

CO

2 R7,

CH

2 CONHR7. CH=CHCH 2 OH, CH=CHCH 2 OR7, CH(OH)CH 3 , CH(OR7)CH 3 , H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, 10 alkynyl, substituted alkynyl, amide, ester, NR7R7, CN, O, S, NHR7, OH, OR7, CHO,

(CH

2 )nOH, (CH 2 )nSH, (CH 2 )nO-alkoxy, (CH 2 )nSR7, (CH 2 )nOR7 (where n = 1, 2, 3, 4, and R7 is a functional group less than or equal to 100000 daltons), (CH 2 )nCO 2 R7 (where R7 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl or substituted alkynyl, and n=l, 2, 3, 4), (CH 2 )nCONR7, 15 CO2R7, CONHR7, CONR IOR7, SR7 (where R7 is a functional group less than or equal to 100000 daltons), SO 3 H, SO 3 R7, SO 2 NHR7, SO 2 N(R7) 2 , SO 2 N(R7) 3 +X (where R7 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion), protein or biomolecule or functional group less than or equal to 100000 daltons; X is O,

H

2 , (H, OH), (H, OR8) S, or a ketone protecting group; M is Inl 3 , In'1 5 or a mixture of 20 In' 1 3 and In 15; Z is a halide , acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, protein or biomolecule or functional group less than or equal to 100000 daltons. M can also be Ag, Ce, Co, Cr, Cu, Dy, Er, Fe, Ga, Hf, Ho, La, Lu. Mo, Mg, Nd, Pb, Pr, Rh, Sb, Sc, Sm, Sn, Tb, Th, Ti, TI, Tm, U, V, Y, Yb or Zr, preferably Pd, Pt, Ga, Al, Ru, 25 Sn or Zn,.

WO 00/00204 PCT/US98/13601 75 Another family of compounds has the following structure: RI R5 R6 R6 N Z N R3 / H N N H H R2 R4 X wherein; 5 RI is CH=CH2, Et, CHO, or COCH 3 R2 is CO 2

CH

3 , CO 2 H, CO 2 R7 (R7 is an alkyl or phenyl group), or an amide R3 is H R4 is H or CO 2

CH

3 R5 is O or NR7 (where R7 is alkyl) 10 R6 is Me XisO M is In 1 3, In 15 or a mixture of In" 3 and In 1 15 Z is a halide . acetate or OH. M can also be Ag, Ce, Co, Cr, Cu, Dy, Er, Fe, Ga, Hf, Ho, La, Lu, Mo, Mg, Nd, Pb, Pr, 15 Rh, Sb, Sc, Sm, Sn, Tb, Th, Ti, T1, Tm, U, V, Y, Yb or Zr, preferably Pd, Pt, Ga, Al, Ru, Sn or Zn. Another family of compounds has the following structure: RI R5 R7 R2 20 where each of R1- R8 is CH2)CH3, CH=CH2), CH=CHCH2N(CH3)2, CH=CHCH2N+(CH3)3 X- (where X is a charge balancing ion), C(X)2C(X)3 (where X is a halogen), CHO, N N' R3 \ M / H N N H R8 R4 R2 20 where each of R1- R8 is CH 2

CH

3 , CH=CH 2 , CH=CHCH 2

N(CH

3 )2, CH=CHCH 2

N*(CH

3

)

3 X- (where X is a charge balancing ion), C(X) 2

C(X)

3 (where X is a halogen), CHO, WO 00/00204 PCT/US98/13601 76 COCH3, CO 2 H, CO2R9, CONHR9, CH=CHCHO, CH 2 Y, (where Y = H, halogen, OH, OR9 or is a functional group less than or equal to 100000 daltons), CH 2

CO

2 R9,

CH

2 CONHR9, CH=CHCH 2 OH, CH=CHCH 2 OR9, CH(OH)CH 3 , CH(OR9)CH 3 , H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, 5 alkynyl, substituted alkynyl, amide, ester, NR9R9, CN, O, S, NHR9, OH, OR9, CHO, (CH,).OH, (CH,)nSH, (CH 2 )nO-alkoxy, (CH,)nSR9, (CH,)nOR9 (where n = 1, 2, 3, 4, and R9 is a functional groups less than or equal to 100000 daltons), (CH 2 )nCO 2 R9 (where R9 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n=l, 2, 3, 4), (CH 2 )nCONHR9, 10 (CH 2 )nCON(R9)2, CO2R9, CONHR9, CONRIOR9, SR9 (where R9 is a functional groups less than or equal to 100000 daltons), SO3H. SO 3 R9, SO 2 NHR9, SO 2 N(R9) 2 ,

SO

2 N(R9)3X - (where R9 is a functional groups less than or equal to 100000 daltons and X is a charge balancing ion), protein or biomolecule or functional group less than or equal to 100000 daltons; M is In 13, In " 5 or a mixture of In 1 3 and In 1 5 ; Z is a halide , acetate, 15 OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, a protein or biomolecule or functional group less than or equal to 100000 daltons. M can also be Ag, Ce, Co, Cr, Cu, Dy, Er, Fe, Ga, Hf, Ho, La, Lu, Mo, Mg, Nd, Pb, Pr, Rh, Sb, Sc, Sm, Sn, Tb, Th, Ti, TI, Tm, U, V, Y, Yb or Zr, preferably Pd, Pt, Ga, Al, Ru, Sn or Zn. 20 Still another family of compounds has the following structure: RI R5R R3 M / H N N H R8 R4 R2 wherein; 25 R I is CH=CH2, Et, CHO, or COCH 3 R5 is O or NR7 (where R7 is alkyl) R7 is Me WO 00/00204 PCT/US98/13601 77 R3 is H R4 and R8 are H, CO 2

CH

3 , CO2,H (or a salt thereof), CO2R7 (R7 is an alkyl or phenyl group), an amide, CH 2

CO

2

CH

3 , CH 2

CO

2 H (or a salt thereof), CO2R9 (R9 is an alkyl or a phenyl group), or an amide 5 R2 is CO 2

CH

3 , CO 2 H, CO 2 R9 (R9 is an alkyl or phenyl group), or an amide M is In 113, In" 5 or a mixture of In 113 and In" 115 Z is a halide, acetate, or OH. M can also be Ag, Ce. Co, Cr, Cu, Dy, Er, Fe, Ga, Hf, Ho, La, Lu, Mo, Mg, Nd, Pb, Pr, Rh, Sb, Sc, Sm, Sn, Tb, Th, Ti, TI, Tmin, U, V, Y, Yb or Zr, preferably Pd, Pt, Ga, Al. Ru, 10 Sn or Zn. Another family of compounds has the following structure: RI R4 R3 R5 P3 \ ,M\ H N N H H A X B R2 where each of R1- R5 is CH 2

CH

3 , CH=CH 2 , CH=CHCH 2

N(CH

3 )2, CH=CHCH 2

N'(CH

3

)

3 15 X (where X is a charge balancing ion), C(X) 2

C(X)

3 (where X is a halogen), CHO,

COCH

3 , CO2H, CO2R6, CONHR6, CH=CHCHO, CH 2 Y, (where Y = H, halogen, OH, OR6 or is a functional group less than or equal to 100000 daltons), CH 2 CO2R6,

CH

2 CONHR6, CH=CHCH 2 OH, CH=CHCH 2 OR8, CH(OH)CH 3 , CH(OR6)CH 3 , H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, 20 alkynyl, substituted alkynyl, amide, ester, NR6R6, CN, O, S, NHR6, OH, OR6, CHO,

(CH

2 )nOH, (CH 2 )nSH, (CH 2 )nO-alkoxy, (CH 2 )nSR6, (CH 2 )nOR6 (where n = 1, 2, 3, 4, and R6 is a functional group less than or equal to 100000 daltons), (CH 2 )nCO 2 R6 (where R6 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n=1, 2, 3, 4), (CH 2 )nCONR6, 25 CO2R6, CONHR6, CONR6R6, SR6 (where R6 is a functional group less than or equal to 100000 daltons), SO 3 H, SO 3 R6, SO 2 NHR6, SO 2 N(R6) 2 , SO 2 N(R6) 3 +X - (where R6 is a WO 00/00204 PCT/US98/13601 78 functional group less than or equal to 100000 daltons), SO 3 H, SO 3 R6, SO 2 NHR6,

SO

2 N(R6) 2 , SO 2 N(R6) 3 X' (where R6 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion), protein or biomolecule or functional group less than or equal to 100000 daltons; X is O, NR6 (where R6 is H, alkyl (1-10 carbons), aryl, 5 substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, an amino acid, an amino acid ester or a functional group less than or equal to 100000 daltons); A and B are O, NH, NR6 or combinations thereof; Z is a halide , acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, protein or biomolecule or functional group less than or equal to 100000 daltons. 10 M can also be Ag, Ce, Co, Cr, Cu, Dy, Er, Fe, Ga, Hf, Ho, La, Lu, Mo, Mg, Nd, Pb, Pr, Rh, Sb, Sc, Sm, Sn, Tb, Th, Ti, TI, Tm, U, V, Y, Yb or Zr, preferably Pd, Pt, Ga, Al, Ru, S or Zn. Another family of compounds has the following structure: 15 RI R4 R5 R3RS NN H N N H A X B R2 Wherein: Each of A and B is O or NR6 (where R6 is an alkyl or phenyl group) RI is CH=CH 2 , Et, CHO, or COCH 3 20 R4 is O or NR6 (where R6 is alkyl) R5 is Me R3 is H R2 is CO 2

CH

3 , CO 2 H, CO2R6 (R6 is an alkyl or phenyl group), or an amide X is O, NR6 (R6 is alkyl, an amino acid, an alcohol containing group, or an ether 25 containing group) M is In"' 3 , In"' 5 or a mixture of In'' 3 and In'1 5 Z is a halide , acetate, OH.

WO 00/00204 PCT/US98/13601 79 M can also be Ag, Ce, Co, Cr, Cu, Dy, Er, Fe, Ga, Hf, Ho, La, Lu, Mo, Mg, Nd, Pb, Pr, Rh, Sb, Sc, Sm. Sn, Tb, Th, Ti, TI, Tm, U, V, Y, Yb or Zr, preferably Pd, Pt, Ga, Al, Ru, Sn or Zn. 5 Another family of compounds has the following structure: RI R5 N N ~ N,~N R6 R3 ,M H N N H R2 R4 X Where each of R1- R6 is CH 2

CH

3 , CH=CH2, CH=CHCH 2

N(CH

3

)

2 , CH=CHCH 2

N+(CH

3

)

3 X- (where X is a charge balancing ion), C(X) 2

C(X)

3 (where X is a halogen), CHO, 10 COCH 3 , CO2H, CO2R7, CONHR7, CH=CHCHO, CH 2 Y, (where Y = H, halogen, OH, OR7 or is a functional group less than or equal to 100000 daltons), CH 2

CO

2 R7,

CH

2 CONHR7, CH=CHCH 2 OH, CH=CHCH 2 OR7, CH(OH)CH 3 , CH(OR7)CH 3 , H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, NR7R7, CN, O, S, NHR7, OH, OR7, CHO, 15 (CH 2 )nOH, (CH 2 )nSH, (CH 2 )nO-alkoxy, (CH 2 )nSR7, (CH 2 )nOR7 (where n = 1, 2, 3, 4, and R7 is a functional groups less than or equal to 100000 daltons), (CH 2 )nCO 2 R7 (where R7 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl. substituted alkenyl, alkynyl, or substituted alkynyl, and n=1, 2, 3, 4), (CH 2 )nCONR7, CO2R7, CONHR7, CONR7R7, SR7 (where R7 is a functional group less than or equal to 20 100000 daltons), SO 3 H, SO 3 R7, SO 2 NHR7, SO 2 N(R7) 2 , SO 2 N(R7) 3 +X (where R7 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion), protein or biomolecule or functional group less than or equal to 100000 daltons; X is O,

H

2 , (H, OH), (H, OR7), S, or a ketone protecting group; M is In' 3 , In " or a mixture of In 1 3 and In 115 ; Z is a halide , acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted 25 alkenyl, alkynyl, substituted alkynyl, protein or biomolecules or functional group less than or equal to 100000 daltons.

WO 00/00204 PCT/US98/13601 80 M can also be Ag, Ce, Co, Cr, Cu, Dy, Er. Fe, Ga. Hf, Ho. La, Lu. Mo, Mg, Nd, Pb. Pr, Rh, Sb, Sc, Sm, Sn, Tb, Th, Ti, TI, Tm, U, V, Y, Yb or Zr, preferably Pd, Pt, Ga, Al, Ru, Sn or Zn. 5 Another family of compounds has the structure: R1 R5 R6 N. ZN R3 ,M H N N H R2 R4 X wherein; 10 RI is CH=CH 2 , Et, CHO, or COCH 3 R6 is O or NR7 (where R7 is an alkyl group) R5 is Me R3 is H R4 is H or CO 2

CH

3 15 R2 is CO 2

CH

3 , CO 2 H, CO2R7 (R7 is an alkyl, phenyl), or an amide XisO M is In 1 3, In' 1 5 or amixture of In' 1 3 and In1 5 Z is a halide , acetate, or OH. M can also be Ag, Ce, Co, Cr, Cu, Dy, Er, Fe, Ga, Hf, Ho, La, Lu, Mo, Mg, Nd, Pb, Pr, 20 Rh, Sb, Sc, Sm, Sn, Tb, Th, Ti, TI, Tm, U, V, Y, Yb or Zr, preferably Pd, Pt, Ga, Al, Ru, Sn or Zn.

WO 00/00204 PCT/US98/13601 81 Another family of compounds has the structure: RI R5 " R6 R3 ,M / H N N H R4 R7 R2 Where each of R1- R7 is CH 2

CH

3 , CH=CH 2 , CH=CHCHzN(CH 3

)

2 , CH=CHCH 2

N+(CH

3

)

3 5 X (where X is a charge balancing ion), C(X) 2

C(X)

3 (where X is a halogen), CHO,

COCH

3 , CO 2 H, CO2R8, CONHR8, CH=CHCHO, CH 2 Y,(where Y = H, halogen, OH, OR8 or is a functional group less than or equal to 100000 daltons), CH 2

CO

2 R8,

CH

2 CONHR8, CH=CHCH 2 OH, CH=CHCH 2 OR8, CH(OH)CH 3 , CH(OR8)CH 3 , H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, 10 alkynyl, substituted alkynyl, amide, ester, NR8R8, CN, O, S, NHR8, OH, OR8, CHO, (CH2)nOH, (CH2)nSH, (CH2)nO-alkoxy, (CH2)nSR8, (CH2)nOR8 (where n = 1, 2, 3, 4, and R8 is a functional groups less than or equal to 100000 daltons), (CH2)nCO2R8 (where R8 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl,substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n=1, 2, 3, 4), 15 (CH2)nCONR8, CO2R8, CONHR8, CONR8R8, SR8 (where R8 is a functional groups less than or equal to 100000 daltons), SO 3 H, SO3R8, SO 2 NHR8, SO 2 N(R8) 2 ,

SO

2 N(R8) 3

+X

- (where R8 is a functional groups less than or equal to 100000 daltons and X is a charge balancing ion), protein or biomolecules or functional groups less than or equal to 100000 daltons; M is In 3 , In l5 or a mixture of In 113 and In 115 ; Z is a halide , 20 acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, protein or biomolecules or functional groups less than or equal to 100000 daltons. Another family of compounds has the structure: WO 00/00204 PCT/US98/13601 82 Ri R5 "- , R6 R3 M N N H H R4 R7 R2 wherein; RI is CH=CH 2 , Et, CHO, or COCH 3 R6 is O, or NR8 (where R8 is alkyl) 5 R5 is Me R3 is H R4 and R7 are H, CO 2

CH

3 , CO 2 H (or a salt thereof), CO2R8 (R8 is alkyl or phenyl), an amide, CH 2

CO

2

CH

3 , CH 2

CO

2 H (or a salt thereof), CO2R8 (R8 is an alkyl or phenyl group) R2 is CO 2

CH

3 , CO 2 H, CO 2 R8 (R8 is alkyl or phenyl), or an amide 10 M is InI 3 , InI 1 5 or a mixture of In 1 3 and Int15 Z is a halide , acetate, OH. M can also be Pd Ag, Ce, Co, Cr, Cu, Dy, Er, Fe, Ga, Hf, Ho, La, Lu, Mo, Mg, Nd, Pb, Pr, Rh, Sb, Sc, Sm, Sn, Tb, Th, Ti, Ti, Tm, U, V, Y, Yb or Zr, preferably Pd, Pt, Ga, Al, Ru, Sn or Zn. 15 Another family of compounds has the following structure: RI R4 R3 / H N N H A X B R2 20 Wherein: R 1 is CH=CH 2 , Et, CHO or COCH 3 WO 00/00204 PCT/US98/13601 83 R4 is Me R3 is H R2 is CO 2

CH

3 , CO2H, CO2R5 (R5 is alkyl or phenyl), or an amide Each of A and B is O or NR5 ( R5 is alkyl) 5 X is O, NR5 (R5 is alkyl. an amino acid, an alcohol containing group, or an ether containing group) M is In" 3 , In115 or a mixture of Ini l 3 and In" 5 M can also be Ag, Al, Ce, Co, Cr, Cu, Dy, Er, Fe, Ga, Hf, Ho, La, Lu, Mo, Mg, Nd, Pb, Pr, Rh, Sb, Sc, Sm, Tb, Th, Ti, TI, Tm, U, V, Y, Yb or Zr, preferably Pd, Pt, Ga, Al, Ru, 10 Sn or Zn. Another family of compounds has the structure: RI R5R 6 R6 N Z N R3 /M / H N N H H R8 R4 R2 Wherein: R1 is CH=CH 2 , Et, CHO or COCH 3 15 Each of R6 and R7 is H or OH R5 is Me R4 is CO 2

CH

3 , CO 2 H, CO 2 R9 (R9 is an alkyl or a phenyl group), an amide,

CH

2 CO2CH 3 , CH 2

CO

2 H, or CH 2

CO

2 R9 (R9 is an alkyl or a phenyl group). R3 is H 20 each of R2 and R8 is CO2CH 3 , CO2H, CO, 2 R9 (R9 is an alkyl or a phenyl group), or an amide M is In'' 3 , In'1 5 or a mixture of In 1 1 3 and In'' 5 Z is a halide , acetate, or OH. M can also be Ag, Ce, Co, Cr, Cu, Dy, Er, Fe, Hf, Ho, La, Lu, Mo, Mg, Nd, Pb, Pr, Rh, 25 Sb, Sc, Sm, Sn, Tb, Th, Ti, TI, Tm, U, V, Y, Yb or Zr, preferably Pd, Pt, Ga, Al, Ru, Sn or Zn.

WO 00/00204 PCT/US98/13601 84 Still another family of compounds has the structure: RI R4 NZN halogen), CHO, COCH3, C~zH, CO I6, N-RC=HHCY weeY=H R3 M\ H N N H H A X B R2 5 wherein each of R1-R5 is CH 2

CH

3 , CH=CH 2 , CH=CHCH 2

N(CH

3

)

2

CH=CHCH

2

N'(CH

3

)

3 X (where X is a charge balancing ion), C(X) 2

C(X)

3 (where X is a halogen), CHO, COCH 3 , COH, CO 2 R6, CONHR6, CH=CHCHO, CH-Y, (where Y = H, halogen. OH or OR6 or is a functional group less than or equal to 100000 daltons),

CH

2

CO

2 R6, CH 2 CONHR6, CH=CHCH 2 OH, CH=CHCH 2 OR6, CH(OH)CH 3 , o10 CH(OR6)CH 3 , H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, NR6R6, CN, O, S, NHR6, OH, OR6, CHO, (CH,)nOH, (CH,)nSH, (CH,)nO-alkoxy, (CH,)nSR6, (CH 2 )nOR6 (where n = 1, 2, 3, 4, and R6 is a functional group less than or equal to 100000 daltons),

(CH

2 )nCOR6 (where R6 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, 15 substituted aryl, alkenyl, substituted alkenyl. alkynyl, or substituted alkynyl, and n=l, 2, 3, 4), (CH 2 )nCONR6, CO2R6, CONHR6, CONR6R6, SR6 (where R6 is a functional group less than or equal to 100000 daltons), SO 3 H, SO 3 R6, SO 2 NHR6, SO 2 N(R6) 2 ,

SO

2 N(R6) 3

'X

- (where R6 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion), protein or biomolecule or functional group less than or equal to 20 100000 daltons; : A and B are O, NH, NR6 or combinations thereof; X is , O, NR6 (where R6 is H, alkyl (1-10 carbons), aryl. substituted aryl. alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, an amino acid, an amino acid ester or a functional group less than or equal to 100000 daltons); M is In 13 , In 15 or a mixture of In 13 and In 15; Z is a halide, acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted 25 alkynyl, protein or biomolecule or functional group less than or equal to 100000 daltons.

WO 00/00204 PCT/US98/13601 85 M can also be Ag, Ce, Co, Cr, Cu, Dy, Er, Fe, Ga, Hf, Ho, La, Lu, Mo, Mg, Nd, Pb, Pr, Rh, Sb, Sc, Sm, Sn, Tb, Th, Ti, TI, Tm, U, V, Y, Yb or Zr, preferably Pd, Pt, Ga, Al, Ru, Sn or Zn. 5 Still another family of compounds has the structure: RI R4 \ R5 R4 is Me R3 iM H N N HA' X B R2 wherein: R1 is CH=CH 2 , Et, CHO or COCH 3 10 R5 is 0 or NR6 (where R6 is alkyl) R4 is Me R3 is H R2 is CO 2

CH

3 , CO 2 H, CO 2 R5 (R5 is alkyl or phenyl), or an amide A and B are O or NR6 (R6 is an alkyl or a phenyl group) 15 X is O, NR6 (R6 is alkyl), an amino acid, an alcohol containing group, or an ether or amine containing group M is In 11 , Ini15 or amixture of In' 13 and In' 115 Z is a halide, acetate. or OH. M can also be Ag, Ce, Co, Cr, Cu, Dy, Er, Fe, Ga, Hf, Ho, La, Lu, Mo, Mg, Nd. Pb, Pr or 20 Rh, preferably Ga, Al, Ru, Sn or Zn. 25 WO 00/00204 PCT/US98/13601 86 Still another family of compounds has the structure: R4 R8, R R3 CR6 R7 A RIO R2 D - N C \ z R12 RI .NC R2 N . N R N N /R13 -q /DR14 C N R3R -D C A R22< A R19 R18C R15 R20R1 R21 RI6 5 Wherein each of R1- R24 is CH 2

CH

3 , CH=CHCH 2

N(CH

3

)

2 , CH=CHCH 2

N+(CH

3

)

3

X

(where X is a charge balancing ion), CH=CH 2 , C(X)2C(X) 3 (where X is a halogen), CHO,

COCH

3 , CO 2 H, CO 2 R25, CONHR25, CH=CHCHO, CH 2 Y, (where Y = H, halogen, OH, OR25 or is a functional group less than or equal to 100000 daltons), CH 2

CO

2 R25,

CH

2 CONHR25, CH=CHCH 2 OH, CH=CHCH 2 OR25, CH(OH)CH 3 , CH(OR25)CH 3 , H, 10 halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, NR25R25, CN, O, S, NHR25, OH, OR25, CHO, (CH,)nOH, (CH 2 ),SH, (CH 2 )nO-alkoxy, (CH,)nSR25, (CH 2 )nOR25 (where n = 1, 2, 3, 4, and R25 is a functional group less than or equal to 100000 daltons), (CH,)nCO2R25 (where R25 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted 15 aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n=1, 2, 3, 4),

(CH

2 )nCON(R25) 2 , (CH 2 )nCONHR25, CO2R25, CONHR25, CONR25R25, SR25 (where R25 is a functional group less than or equal to 100000 daltons), SO 3 H, SO 3 R25,

SO

2 NHR25, SO 2 N(R25) 2 , SO 2 N(R25) 3 X (where R25 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion), protein or biomolecule or 20 functional group less than or equal to 100000 daltons; A, B, C, D are: C, N, O0, O, S, Te, P, N (R25)X - (where R25 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion), or combinations thereof; M is In" 3 , In 15 or a mixture of In" 1 3 and In 5; Z is a halide , acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl substituted alkynyl, protein or biomolecule or functional group less than 25 or equal to 100000 daltons.

WO 00/00204 PCT/US98/13601 87 M can also be Pd or Ga. Yet another family of compounds has the structure: o 0 x p 2 R * B R3 AX N/ o \ B A N I. B ' R RI ZN R4 N , .M\ ,N R8 N N R5 B A N 0 X R7 R6 X 0 0 Wherein each of Rl-R8 is CH 2

CH

3 , CH=CH2, CH=CHCH 2

N(CH

3

)

2 , 5 CH=CHCH 2

N*(CH

3

)

3 X (where X is a charge balancing ion), C(X) 2

C(X)

3 (where X is a halogen), CHO, COCH 3 , CO 2 H, CO2R9, CONHR9, CH=CHCHO, CH 2 Y, (where Y = H, halogen, OH, OR9 or is a functional group less than or equal to 100000 daltons),

CH

2

CO

2 R9, CH 2 CONHR9, CH=CHCH 2 OH, CH=CHCH 2 OR9, CH(OH)CH 3 , CH(OR9)CH 3 , H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, 10 substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, NR9R9, CN, O, S, NHR9, OH, OR9, CHO, (CH,)nOH, (CH,)nSH, (CH,)nO-alkoxy,

(CH

2 )nSR9, (CH2)nOR9 (where n = 1, 2, 3, 4, and R9 is a functional group less than or equal to 100000 daltons),

(CH

2 )nCO 2 R9 (where R9 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n= 1, 2, 3, 15 4), (CHz)nCONHR9, (CH,)nCON(R9) 2 , CO2R9, CONHR9, CONR9R9, SR9 (where R9 is a functional group less than or equal to 100000 daitons), SO 3 H, SO 3 R9, SO 2 NHR9,

SO

2 N(R9) 2 , SO 2 N(R9) 3 +X (where R9 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion), protein or biomolecule or functional group less than or equal to 100000 daltons. 20 A, B, C, D are; C, N, 0

+

, O, S, Te, P, N+(R9)X (where R9 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion), or combinations thereof.; M is In 3, In"' or a mixture of In' 13 and In' 15; Z is a halide, acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, protein or biomolecule or functional group less than or equal to 100000 daltons; X is O, NR9 (where WO 00/00204 PCT/US98/13601 88 R9 is H, alkyl (1-10 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, an amino acid, an amino acid ester or a functional group less than or equal to 100000 daltons). M can also be Pd or Ga. 5 Yet another family of compounds has the structure: R4 R9 SR5 R8, R3- DEF R6 R7\ C E-RIO B A F RI B , .N RI2 N M/ ,N 2 N N / R13 N /A ,R14 R21- DC \ C C. B, B -@ C I RI9 RI8 D-RI5 R20 F -E R17 IR16 RI6 wherein each of R1-R22 is CH 2

CH

3 , CH=CH 2 , CH=CHCH 2

N(CH

3

)

2 10 CH=CHCH 2

N-(CH

3

)

3 X- (where X is a charge balancing ion), C(X) 2

C(X)

3 (where X is a halogen), CHO, COCH 3 , CO2H, CO2R23, CONHR23, CH=CHCHO, CH2Y. (where Y = H, halogen, OH, OR23 or is a functional group less than or equal to 100000 daltons), CH2CO2R23, CH2CONHR23, CH=CHCH 2 OH, CH=CHCH2OR23,

CH(OH)CH

3 , CH(OR23)CH 3 , H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, 15 substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, NR23R23, CN, O, S, NHR23, OH, OR23, CHO, (CH 2 )nOH, (CH 2 )nSH, (CH 2 )nO-alkoxy, (CH 2 )nSR23,

(CH

2 )nOR23 (where n = 1, 2, 3, 4, and R23 is a functional group less than or equal to 100000 daltons), (CH 2 )nCO 2 R23 (where R23 is H, a physiologically acceptable salt. alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted 20 alkynyl, and n=l, 2, 3, 4), (CH 2 )nCONHR23, (CH 2 )nCON(R23) 2 , CO2R23, CONHR23, CONR23R23, SR23 (where R23 is a functional group less than or equal to 100000 daltons), SO 3 H, SO 3 R23, SO 2 NHR23, SO 2 N(R23) 2 , SO 2 N(R23) 3 + X - (where R23 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion), protein or biomolecule or functional group less than or equal to 100000 daltons; A, B, C, 25 D, E and F are C, N, 0

+

, O, S, Te. P, N+(R23)X

-

(where R23 is a functional group less WO 00/00204 PCT/US98/13601 89 than or equal to 2000 daltons and X is a charge balancing ion), or combinations thereof; M is In " 3 , In'" 5 or a mixture of In' t 3 and In "5; Z is a halide , acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, protein or biomolecule or functional group less than or equal to 100000 daltons. 5 M can also be Pd or Ga. Another family of compounds has the structure: R4 44,R5 E F R8 R3- D , R6 R7,, -' B A C. C D -R9 R2 Ni N Ri R N N RIO R18 N N /Rlt A A RI7- D D-R12 C: B B C RI6 R15 R14 ~13 10 wherein each of R1-R18 is CH 2

CH

3 , CH=CH 2 , CH=CHCH 2

N(CH

3

)

2 ,

CH=CHCH

2

N'(CH

3

)

3 X (where X is a charge balancing ion), C(X) 2

C(X)

3 (where X is a halogen), CHO. COCH3, CO2H, COR19, CONHR19, CH=CHCHO, CH2Y, (where Y = 15 H, halogen, OH, OR19 or is a functional group less than or equal to 100000 daltons),

CH

2

CO

2 R19, CH 2 CONHRI9, CH=CHCH 2 OH, CH=CHCH 2 ORI9, CH(OH)CH 3 , CH(OR19)CH 3 , H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, NR19R19, CN, 0, S, NHR19, OH, OR19, CHO, (CH 2 )nOH, (CH 2 )nSH, (CH2)nO-alkoxy, (CH 2 )nSR19, or 20 (CH2)nOR19 (where n = 1, 2, 3, 4, and R19 is a functional group less than or equal to 100000 daltons), (CH 2 )nCO 2 RI9 (where R19 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n=1, 2, 3, 4), (CH 2 )nCONHR19, (CH2)nCON(R19) 2 , CO 2 R19, CONHR19, CONR19R19, SR19 (where R19 is a functional group less than or equal to 2000 daltons), 25 SO 3 H, SO 3 R19, SO 2 NHR19, SO 2 N(R19) 2 , SO 2 N(RI9) 3

+

X (where R19 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion), protein or WO 00/00204 PCT/US98/13601 90 biomolecule or functional group less than or equal to 100000 daltons; A, B, C, D, E, F are CH, N, 0

+

, O, S, Te, P, N+(R19)X (where R19 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion), or combinations thereof; M is In 1 1 3 , In 115 or a mixture of In' 13 and In 1 15; Z is a halide , acetate, OH, alkyl, aryl, substituted aryl, 5 alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, protein or biomolecule or functional group less than or equal to 100000 daltons. M can also be Pd or Ga. Another family of compounds has the structure: 10 R4 I4,R5 E :F R8 R3- D \ ,R6 R7\ C - A D-R9 R2A N B R RIO N IR N R20\ N N /RuI N / R12 R19- CDB B C 'RI7 R16 F D-R I3 R18 ,F E R15 I R14 wherein each of R1-R20 is CH 2

CH

3 , CH=CH 2 , CH=CHCH 2

N(CH

3

)

2 ,

CH=CHCH

2

N+(CH

3

)

3 X (where X is a charge balancing ion), C(X) 2

C(X)

3 (where X is a halogen), CHO, COCH 3 , CO 2 H, CO2R21, CONHR21, CH=CHCHO, CH 2 Y, (where Y = 15 H, halogen, OH, OR21 or is a functional group less than or equal to 100000 daltons).

CH

2 CO2-R21, CH 2 CONHR21, CH=CHCH 2 OH, CH=CHCH 2 OR21, CH(OH)CH 3 , CH(OR21)CH3, H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, NR21R21, CN, O, S, NHR21, OH, OR21, CHO, (CH 2 )nOH, (CH 2 )nSH, (CH 2 )nO-alkoxy, (CH 2 )nSR21, 20 (CH 2 )nOR21 (where n = 1, 2, 3, 4, and R21 is a functional group less than or equal to 100000 daltons), (CH 2 )nCO 2 R21 (where R21 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n=1, 2, 3, 4), (CH 2 )nCONHR21, (CH 2 )nCON(R21) 2 , CO2R21, CONHR21, CONR21R21, SR21 (where R21 is a functional group less than or equal to 100000 25 daltons), SO 3 H, SO 3 R21, SO 2 NHR21, SO 2 N(R21) 2 , SO 2 N(R21) 3 +X - (where R21 is a WO 00/00204 PCT/US98/13601 91 functional group less than or equal to 100000 daltons and X is a charge balancing ion), protein or biomolecule or functional group less than or equal to 100000 daltons; A, B, C, D, E, F are: C, N, O0, O, S, Te, P, N+(R21)X - (where R21 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion), or combinations thereof; M is 5 In' 3 , In' 1 5 or a mixture of In' 3 and In'15; Z is a halide , acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, protein or biomolecule or functional group less than or equal to 100000 daltons. M can also be Pd or Ga. 10 Still another family of compounds has the following structure: R4 D' ER5 R3-C' E R 8

R

9 R F-R6 R7 I BC, R. R24 N\ .M,, ,N k12 R2- N N 13 ER1F R22-I N / 0 B D-R14 1 A Z1 I R21 BA\ RlSF R20 RI9 ~ ,C-R15 / ED R17 I R16 where each of R1-R24 is CH 2

CH

3 , CH=CH2, CH=CHCH 2

N(CH

3

)

2 , CH=CHCH 2

N+(CH

3 )3 X (where X is a charge balancing ion), C(X) 2

C(X)

3 (where X is a halogen), CHO, 15 COCH 3 , CO 2 H, CO2R25, CONHR25, CH=CHCHO, CH 2 Y, (where Y = H, halogen, OH, OR25 or is a functional group less than or equal to 100000 daltons), CH 2

CO

2 R25,

CH

2 CONHR25, CH=CHCH 2 OH, CH=CHCH 2 OR25, CH(OH)CH 3 , CH(OR25)CH 3 , H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, NR25R25, CN, O, S, NHR25, OH, OR25, 20 CHO, (CH 2 )nOH, (CH 2 )nSH, (CH 2 )nO-alkoxy, (CH 2 )nSR25, (CH 2 )nOR25 (where n = 1, 2, 3, 4, and R25 is a functional group less than or equal to 100000 daltons), (CH 2 )nCO 2 R25 (where R25 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n=1, 2, 3, 4),

(CH

2 )nCONHR25,

(CH

2 )nCON(R25)2, CO 2 R25, CONHR25, CONR25R25, SR25 (where WO 00/00204 PCT/US98/13601 92 R25 is a functional group less than or equal to 100000 daltons), SO 3 H, SO 3 R25,

SO

2 NHR25, SO 2 N(R25) 2 , SO 2 N(R25)3X - (where R25 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion), protein or biomolecule or functional group less than or equal to 100000 daltons; A, B, C, D, E, F are C, N, O0, O, S, 5 Te, P, N+(R25)X - (where R25 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion), or combinations thereof; M is In' 3 , In' 5 or a mixture of In' 13 and In' 15; Z is a halide, acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, protein or biomolecule or functional group less than or equal to 100000 daltons. 10 M can also be Pd or Ga. Still another family of compounds has the structure: R7 I7 R6R 1 0 I 11 C-B' B-CR12 R5-A' R4 8 13 A -- R A R3-C" \ N / "C-RI4 B - Z BR R2Y N, N- RI5 RR1 R2 N N R16 R. 2 .- R17 R31k N N ,R18 B -B R30-C / N \ ,,C-R19 A R24 A R 9 'R20 R29 A / R25 B A-R2 1 R28' "C-B BC ' R2 3 R27 6 R23 22 15 where each of R1-R32 is CHCH 3 , CH=CH 2 , CH=CHCH 2 N(CH3) 2 , CH=CHCH 2

N'(CH

3

)

3 X (where X is a charge balancing ion), C(X) 2

C(X)

3 (where X is a halogen), CHO,

COCH

3 , CO 2 H, CO2R33, CONHR33. CH=CHCHO, CHY, (where Y = H, halogen, OH. OR33 or is a functional group less than or equal to 100000 daltons). CH2CO2R33, 20 CH 2 CONHR33, CH=CHCH 2 OH, CH=CHCH2OR33,

CH(OH)CH

3 , CH(OR33)CH 3 , H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, NR33R33, CN, O, S, NHR33, OH, OR33, CHO, (CH,)nOH, (CH,)nSH, (CHz)nO-alkoxy,

(CH

2 )nSR33, (CH,)nOR33 (where n = 1, 2, 3, 4, and R33 is a functional group less than or equal to 100000 daltons), (CH 2 )nCO 2 R33 25 (where R33 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted WO 00/00204 PCT/US98/13601 93 aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n=l, 2, 3, 4), (CH,)nCONHR33,

(CH

2 )nCON(R33) 2 , CO2R33, CONHR33, CONR33R33, SR33 (where R33 is a functional group less than or equal to 100000 daltons), SO 3 H, SO 3 R33,

SO

2 NHR33, SO 2 N(R33) 2 , SO 2 N(R33) 3

*

X - (where R33 is a functional group less than or 5 equal to 100000 daltons and X is a charge balancing ion), protein or biomolecule or functional group less than or equal to 100000 daltons; A, B, C are; C, N, O', O, S, Te, P, N+(R33)X - (where R33 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion), or combinations thereof; M is In 13 'n115 or a mixture of In'l 3 and In' 15; Z is a halide , acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, 10 alkynyl, substituted alkynyl, protein or biomolecule or functional group less than or equal to 100000 daltons. M can also be Pd or Ga. Still another family of compounds has the structure: 15 R3 R4 R5 R6 /V y RI8 xU R2-U V-R7 x \ RI NN R8 N M N R17 N N R9 Y X // N " \\ RI6-V\ U xU-R10 UsX Y I R14 R13 R11 RI5 where each of R1 I-RI 8 is CH 2

CH

3 , CH=CH 2 , CH=CHCH 2

N(CH

3

)

2 , CH=CHCHN'(CH 3

)

3 X (where X is a charge balancing ion), C(X) 2

C(X)

3 (where X is a halogen), CHO,

COCH

3 , COzH, CO2R19, CONHRI9, CH=CHCHO, CH 2 Y, (where Y = H, halogen, OH, 20 OR19 or is a functional group less than or equal to 100000 daltons), CH 2

CO

2 R19,

CH

2 CONHR19, CH=CHCHzOH, CH=CHCH 2 OR19, CH(OH)CH 3 , CH(OR19)CH 3 , H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, NRI9R19, CN, O, S, NHRI9, OH, OR19, CHO, (CH 2 )nOH, (CH 2 )nSH, (CH,)nO-alkoxy, (CH2)nSR19, (CH,)nOR19 (where n = 1, 2, 25 3, 4, and R19 is a functional group less than or equal to 100000 daltons), (CH,)nCO 2 R19 (where R19 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted WO 00/00204 PCT/US98/13601 94 aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n= 1, 2, 3, 4), (CH,)nCONHR19, (CH 2 )nCON(R19) 2 , CO 2 R19, CONHR19, CONR10RI9, SRI9 (where R19 is a functional group less than or equal to 100000 daltons), SO 3 H, SO 3 R19,

SO

2 NHR19, SO2N(R19)2, SO 2 N(R19) 3

+X

- (where R19 is a functional group less than or 5 equal to 100000 daltons and X is a charge balancing ion), protein or biomolecule or functional group less than or equal to 100000 daltons. U, V, X, Y are C, N, O0, O, S, Te, P, N+(R19)X - (where R19 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion), or combinations thereof; M is In" 3 , In" 5 or a mixture of In" 113 and In" 5 ; Z is a halide , acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted 10 alkenyl, alkynyl, substituted alkynyl, protein or biomolecule or functional group less than or equal to 100000 daltons. M can also be Pd or Ga. Another family of compounds has the structure: 15 R3 R9 R4 A N N R2 ~N\ N1 RI M R6 R8 R7 where each of Rl1-R9 is CH 2

CH

3 , CH=CH 2 , CH=CHCH 2

N(CH

3

)

2 , CH=CHCH 2

N+(CH

3

)

3 X (where X is a charge balancing ion), C(X) 2

C(X)

3 (where X is a halogen), CHO, 20 COCH 3 , CO 2 H, CO 2 RIO, CONHR10, CH=CHCHO, CH2Y, (where Y = H, halogen, OH, ORIO or is a functional group less than or equal to 100000 daltons), CH 2

CO

2 R10,

CH

2 CONHRIO, CH=CHCH 2 OH, CH=CHCH 2 OR10, CH(OH)CH 3 , CH(OR10)CH 3 , H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, NR1OR10, CN, OH, OR10, CHO, (CH 2 )nOH, 25 (CH 2 )nSH, (CH 2 )nO-alkoxy, (CH 2 )nSR10, (CH,)nOR0IO (where n = 1, 2, 3, 4, and RO10 is a functional group less than or equal to 100000 daltons), (CHz)nCO 2 R10 (where RO10 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n=1, 2, 3, 4), (CH 2 )nCONHR10, (CH),CON(R10) 2 , CO 2 R10, CONHR10, CONR10R10, SRIO (where RIO is a functional WO 00/00204 PCT/US98/13601 95 group less than or equal to 100000 daltons), SO 3 H, SO 3 RIO, SO 2 NHR10, SO 2

N(RIO)

2 ,

SO

2 N(RO10) 3 +X (where RO10 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion), protein or biomolecule or functional group less than or equal to 100000 daltons; M is In" ' 3 , In 115 or a mixture of In' l 3 and In 11 5 5 M can also be Ga. Still another family of compounds has the structure: RI R2 RI1 R3 R12 \/ R4 RIO M / R5 -N N R9 - / R6 R8 R7 where each of RI-RI2 is CH 2

CH

3 , CH=CH 2 , CH=CHCH 2

N(CH

3

)

2 , CH=CHCH 2

N+(CH

3

)

3 10 X (where X is a charge balancing ion), C(X) 2

C(X)

3 (where X is a halogen), CHO,

COCH

3 , CO 2 H, CO2R13, CONHR13, CH=CHCHO, CH 2 Y, (where Y = H, halogen, OH, OR13 or is a functional group less than or equal to 100000 daltons), CH 2

CO

2 R13,

CH

2 CONHR13, CH=CHCH 2 OH, CH=CHCH 2 OR13, CH(OH)CH 3 , CH(OR13)CH 3 , H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, 15 alkynyl, substituted alkynyl, amide, ester, NR13R13, CN, OH, OR13, CHO, (CH,)nOH, (CH,)nSH , (CH,)nO-alkoxy, (CH 2 )nSR13, (CH,)nOR13 (where n = 1, 2, 3. 4, and R13 is a functional group less than or equal to 100000 daltons), (CH 2 )nCOR13 (where R13 is H, a physiologically acceptable salt,- alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n=l, 2, 3, 4), (CH2)nCONHR13, 20 (CH,)nCON(RI3) 2 , CO 2 R13, CONHR13, CONR13R13, SR13 (where R13 is a functional group less than or equal to 100000 daltons), SO 3 H, SO 3 R13, SO 2 NHR13, SO 2 N(R13) 2 ,

SO

2 N(R13) 3

'X

- (where R13 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion), protein or biomolecule or functional group less than or equal to 100000 daltons; M is In 13, In"' or a mixture of In" 3 and In' 15 ; Z is a halide, acetate, 25 OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, protein or biomolecule or functional group less than or equal to 100000 daltons.

WO 00/00204 PCT/US98/13601 96 M can also be Pd or Ga. Yet another family of compounds has the structure: R R4 R5 R13 R2 \N 1 '- N / R6 R11 M n+_N N" ' R7 RI I5 RIO R R8 R9 5 Where each of RI- R15 is CH2CH3, CH=CH2, CH=CHCH2N(CH3)2 ,

CH=CHCH

2

N+(CH

3

)

3 X (where X is a charge balancing ion), C(X) 2

C(X)

3 (where X is a halogen), CHO, COCH 3 , CO 2 H, CO2R16, CONHR16, CH=CHCHO, CHY, (where Y = H, halogen, OH, OR16 or is a functional group less than or equal to 100000 daltons),

CH

2

CO

2 R16, CH 2 CONHR16, CH=CHCH 2 OH, CH=CHCH20R16, CH(OH)CH 3 , 10 CH(OR16)CH 3 , H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, NR16R16, CN, O, S, NHR16, OH, OR16, CHO, (CH 2 )nOH, (CH 2 )nSH, (CH 2 )nO-alkoxy, (CH 2 )nSR16, (CH,)nOR16 (where n = 1, 2, 3, 4, and R16 is a functional group less than or equal to 100000 daltons), (CH 2 )nCO 2 R16 (where R16 is H, a physiologically acceptable salt, alkyl 15 (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n=1, 2, 3, 4), (CH,)nCONHR16, (CH,)nCON(R16) 2 , CO 2 R16, CONHR16, CONRI6R16, SR16 (where R16 is a functional group less than or equal to 100000 daltons), SO 3 H, SO 3 R16, SO 2 NHR16, SO 2 N(R16) 2 , SO 2 N(R16)3*X - (where R16 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion), 20 protein or biomolecule or functional group less than or equal to 100000 daltons; M is In' 13 In15 or a mixture of In 11 3 and In15; Z is a halide , acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, protein or biomolecule or functional group less than or equal to 100000 daltons. M can also be M is Ag, Ce, Co, Cr, Cu, Dy, Er, Fe, Ga, Hf, Ho, La, Lu, Mo, Mg, Nd, Pb, 25 Pr or Rh, preferably Pd, Pt, Ga, Al, Ru, Sn or Zn.

WO 00/00204 PCT/US98/13601 97 Yet another family of compounds has the following structure: R3 R1R4 - R5 R12 R2 . \ R6 N 'n+ N R R7 9 RIO R8 R8 R13 5 where each of R l-R14 is CH 2

CH

3 , CH=CH 2 , CH=CHCH2,N(CH 3

)

2 , CH=CHCH 2

N'(CH

3

)

3 X (where X is a charge balancing ion), C(X) 2

C(X)

3 (where X is a halogen), CHO,

COCH

3 , CO2H, CO2R15, CONHR15, CH=CHCHO, CH 2 Y, (where Y = H, halogen, OH, OR15 or is a functional group less than or equal to 100000 daltons), CH2CO2R15,

CH

2 CONHR15, CH=CHCH 2 OH, CH=CHCH 2 ORI5, CH(OH)CH 3 , CH(OR15)CH 3 , H, 10 halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, NR15R15, CN, O, S, NHRI5, OH, OR15, CHO, (CH 2 )nOH, (CH 2 )nSH, (CH2)nO-alkoxy, (CH2)nSR15, (CH 2 )nOR15 (where n = 1, 2, 3, 4, and R15 is a functional group less than or equal to 100000 daltons), (CH')nCO 2 RI5 (where R15 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted 15 aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n= 1, 2, 3, 4),

(CH

2 )nCONHR15, (CH 2 )nCON(R15) 2 , CO2R15, CONHR15, CONR15R15, SR15 (where R15 is a functional group less than or equal to 100000 daltons), SO 3 H, SO 3 R15,

SO

2 NHR15, SO 2 N(R15) 2 , SO 2 N(R15) 3 X - (where R15 is a functional groups less than or equal to 100000 daltons and X is a charge balancing ion), protein or biomolecule or 20 functional group less than or equal to 100000 daltons; M is In 3 , In 115 or a mixture of In" 3 and In " 115 Z is a halide , acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, protein or biomolecule or functional group less than or equal to 100000 daltons. M can also be Ag, Ce, Co, Cr, Cu, Dy, Er, Fe, Ga, Hf, Ho, La, Lu, Mo, Mg, Nd, Pb, Pr or 25 Rh, preferably Pd, Pt, Ga, Al, Ru, Sn or Zn.

WO 00/00204 PCT/US98/13601 98 Still another family of compounds has the following stucture: R3 R11 R13 R4 R2\ N \ R5 RIO M, /n R12 N" N RI\ -N/ /R6 R8 R9 RI15 R7 5 where each of RI-R15 is CH 2

CH

3 , CH=CH 2 , CH=CHCHzN(CH 3

)

2 , CH=CHCH 2

N'(CH

3

)

3 X- (where X is a charge balancing ion), C(X) 2

C(X)

3 (where X is a halogen), CHO,

COCH

3 , CO2H, CO2R16, CONHR16, CH=CHCHO, CH 2 Y, (where Y = H, halogen, OH, OR16 or is a functional group less than or equal to 100000 daltons), CH2CO2R16,

CH

2 CONHR16, CH=CHCHzOH, CH=CHCH 2 OR16, CH(OH)CH 3 , CH(OR16)CH 3 , H, 10 halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, NR16R16, CN, O, S, NHR16, OH, OR16, CHO, (CH 2 )nOH, (CH 2 )nSH, (CH2)nO-alkoxy, (CH,)nSR16, (CH 2 )nOR16 (where n = 1, 2, 3, 4, and R16 is a functional group less than or equal to 100000 daltons), (CH2)nCO 2 R16 (where R16 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted 15 aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n=l1, 2, 3, 4), (CH,)nCONHR16, (CH,)nCON(R16) 2 , CO2R16, CONHRI6, CONR16R16, SR16 (where R16 is a functional group less than or equal to 100000 daltons), SO 3 H, SO 3 R16, SONHR16, SO 2 N(R16) 2 , SO 2 N(R16) 3

'

X - (where R16 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion), protein or biomolecule or 20 functional group less than or equal to 100000 daltons; M is In 113 , In"5 or a mixture of In i 3 and In" 115 ; Z is a halide , acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, protein or biomolecule or functional group less than or equal to 100000 daltons. M can also be Ag, Ce. Co, Cr, Cu, Dy, Er, Fe, Ga, Hf, Ho, La, Lu, Mo, Mg, Nd, Pb, Pr, or 25 Rh, preferably Pd, Pt, Ga, Al, Ru, Sn or Zn.

WO 00/00204 PCT/US98/13601 99 Yet other families of compounds have the following structure: R4 R5 R3 R6 RI N / R7 N RIO R9 8 5 Where each of R1-R12 is CH 2

CH

3 , CH=CH 2 , CH=CHCH 2 N(CH3) 2 ,

CH=CHCH

2

N+(CH

3

)

3 X (where X is a charge balancing ion), C(X) 2

C(X)

3 (where X is a halogen), CHO, COCH 3 , CO 2 H, CO2R13, CONHR13, CH=CHCHO,

CH

2 Y, (where Y = H, halogen, OH, OR13 or is a functional group less than or equal to 100000 daltons), CHCO2RI3, CH2CONHR13, CH=CHCH 2 OH, CH=CHCH2-0R13,

CH(OH)CH

3 , 10 CH(OR13)CH 3 , H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, NR13R13, CN, O, S, NHR13, OH, OR13, CHO, (CH 2 )nOH, (CH 2 )nSH, (CH 2 ),O-alkoxy, (CH 2 )nSR13,

(CH

2 )nOR13 (where n = 1, 2, 3, 4, and R1I3 is a functional group less than or equal to 100000 daltons), (CH 2 )nCO 2 R13 (where R13 is H, a physiologically acceptable salt, alkyl 15 (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n=l, 2. 3, 4), (CH 2 )nCONHR13, (CH 2 )nCON(R13) 2 , CO2R13, CONHR13, CONR13RI3, SR13 (where R13 is a functional group less than or equal to 100000 daltons), SO 3 H, SO 3 R13, SO 2 NHRI3, SO 2 N(R13) 2 , SO 2 N(R13) 3 'X (where R13 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion), 20 protein or biomolecule or functional group less than or equal to 100000 daltons; M is In 13 , In " 5 or a mixture of In' 13 and In 1 5 ; Z is a halide , acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, protein or biomolecule or functional group less than or equal to 100000 daltons. M can also be Pd, Pt, Ga or Al.

WO 00/00204 PCT/US98/13601 100 Another family of compounds has the following structure: R6 R7 R4 R5 - R8 R 4 R2 B N RIO 10 N N / R14 11 R13 R12 15 Where each of R1-RI4 is CH 2

CH

3 , CH=CH2, CH=CHCH 2

N(CH

3

)

2 ,

CH=CHCH

2

N'(CH

3

)

3 X (where X is a charge balancing ion), C(X) 2

C(X)

3 (where X is a halogen), CHO, COCH 3 , CO 2 H, CO2R15, CONHR15, CH=CHCHO, CH 2 Y, (where Y = H, halogen, OH, OR15 or is a functional group less than or equal to 100000 daltons), 20 CH 2 CO2R15, CH 2 CONHRI5, CH=CHCH 2 OH, CH=CHCH 2 OR15, CH(OH)CH 3 , CH(OR15)CH 3 , H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, NR15R15, CN, O, S, NHR15, OH, OR15, CHO, (CH,)nOH, (CHz)nSH, (CH 2 )nO-alkoxy, (CH,)nSR15, (CH),,OR15 (where n = 1, 2, 3, 4, and R15 is a functional group less than or equal to 25 100000 daltons), (CH,)nCO 2 R15 (where R15 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n=1, 2, 3, 4), (CH,)nCONHR15,

(CH

2 )nCON(R15) 2 , CO 2 R15, CONHR15, CONR15R15, SR15 (where R15 is a functional group less than or equal to 100000 daltons), SO 3 H, SO 3 R15, SO 2 NHR15, SO 2 N(R15) 2 , SO 2 N(R15) 3 +X - (where R15 is a 30 functional group less than or equal to 100000 daltons and X is a charge balancing ion), protein or biomolecule or functional group less than or equal to 100000 daltons; A, B, C, D are; C, N, O0, O, S, Te, P, N+(R15)X (where R15 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion), or combinations thereof; M is In 113 , In 115 or a mixture of In 113 and In' 15 ; Z is a halide , acetate, OH, alkyl, aryl, 35 substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, protein or biomolecule or functional group less than or equal to 100000 daltons. M can also be Pd, Pt, Ga or Al.

WO 00/00204 PCT/US98/13601 101 Yet another family of compounds has the following structure: R12 I RII R2 R3 R13 ,C-A RI B D R4 I I N_ - R RI4 A-. 1i . II RI4,A , , ,z IM-N I R .. IGH N R6 RI 'Fy RIR10 7 R16 F R1 R18 R9 R8 R17 5 Where each of Rl1-R18 is CH2CH 3 , CH=CH 2 , CH=CHCH 2

N(CH

3

)

2 ,

CH=CHCH

2

N+(CH

3

)

3 X- (where X is a charge balancing ion), C(X)2C(X) 3 (where X is a halogen), CHO, COCH 3 , CO 2 H, CO 2 R19, CONHR19, CH=CHCHO, CH 2 Y, (where Y = o10 H, halogen, OH. OR19 or is a functional group less than or equal to 100000 daltons),

CH

2 CO2R19, CH 2 CONHR19, CH=CHCH 2 OH, CH=CHCH20R19,

CH(OH)CH

3 , CH(OR19)CH 3 , H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, NR19R19, CN, O, S, NHR19, OH, OR19, CHO, (CH 2 )nOH, (CH 2 )nSH, (CH 2 )nO-alkoxy, (CH 2 )nSR19, 15 (CH,)nOR19 (where n = 1, 2, 3, 4, and R19 is a functional group less than or equal to' 100000 daltons), (CH 2 )nCOzR19 (where R19 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl. and n=l. 2, 3, 4), (CH,)nCONHR19, (CH,)nCON(R19) 2 , CO2R19, CONHR19, CONRI9R19, SR19 (where R19 is a functional group less than or equal to 100000 20 daltons), SO 3 H, SO 3 R19, SO 2 NHR19, SO 2 N(R19) 2 , SO 2 N(R19) 3

+

X- (where R19 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion), protein or biomolecule or functional group less than or equal to 100000 daltons; A, B, C, D, E, F, G, H are; C, N, 0

+

, O, S, Te, P, N+(R19)X - (where R1I9 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion) or combinations thereof; 25 M is In' 13, In' 5 or a mixture of In1 3 and In 1 1 5 ; Z is a halide , acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, protein or biomolecule or functional group less than or equal to 100000 daltons.

WO 00/00204 PCT/US98/13601 102 M can also be Pd, Pt, Ga or Al. Still another family of compounds has the following structure: R3 RI1 R4 R2 R5 NJN~ RIO in R12 N N RI \~ /R6 R8 - R7 R9 5 Where each of RI-R12 is CH 2

CH

3 , CH=CH2, CH=CHCH 2

N(CH

3

)

2 X,

CH=CHCH

2

N'(CH

3

)

3 X (where X is a charge balancing ion), C(X) 2

C(X)

3 (where X is a halogen), CHO, COCH 3 , CO 2 H, CO 2 R13, CONHR13, CH=CHCHO,

CH

2 Y, (where Y = H, halogen, OH, ORI3 or is a functional group less than or equal to 100000 daltons), CH2CO2R13, CH 2 CONHR13, CH=CHCH 2 OH, CH=CHCH 2 OR13, CH(OH)CH 3 , to10 CH(OR13)CH 3 , H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, NR13R13, CN, O, S, NHR13, OH, OR13, CHO, (CH 2 ),OH, (CH 2 )nSH, (CH 2 )nO-alkoxy, (CH2),SR13, (CH,)nOR13 (where n = 1, 2, 3, 4, and R13 is a functional group less than or equal to 100000 daltons), (CH,)nCO 2 R13 (where R13 is H, a physiologically acceptable salt, alkyl 15 (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n=l1, 2, 3, 4), (CH 2 )nCONHR13, (CH 2 )nCON(R13)2, CO 2 R13, CONHR13, CONR13R13, SRI3 (where R13 is a functional group less than or equal to 100000 daltons), SO 3 H, SO 3 R13, SO 2 NHR13, SO 2 N(R13) 2 , SO 2 N(R13)3' X - (where R13 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion). 20 protein or biomolecule or functional group less than or equal to 100000 daltons; Z is halide, acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, protein or biomolecule or functional group less than or equal to 100000 daltons.

WO 00/00204 PCT/US98/13601 103 Another family of compounds has the following structure: R3 R14 R4 R2 R5 NZ N R13 in R15 N N RI \' R6 R12 R7 RI2 R7 Rll R8 RIO R9 5 where each of R1-R15 is CH 2 CH3, CH=CH 2 , CH=CHCH 2

N(CH

3

)

2 , CH=CHCH 2

N+(CH

3

)

3 X- (where X is a charge balancing ion), C(X) 2

C(X)

3 (where X is a halogen), CHO,

COCH

3 , CO 2 H, CO 2 R16, CONHR16, CH=CHCHO, CH 2 Y, (where Y = H, halogen, OH, OR16 or is a functional group less than or equal to 100000 daltons), CH 2

CO

2 R16,

CH

2 CONHR16, CH=CHCH 2 OH, CH=CHCH 2 OR16, CH(OH)CH 3 , CH(OR16)CH 3 , H, 10 halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, NR16R16, CN, O, S, NHR16, OH, OR16, CHO, (CH 2 ),OH, (CH 2 )nSH, (CH 2 )nO-alkoxy, (CH 2 )nSR16, (CH 2 )nOR16 (where n = 1, 2, 3, 4, and R16 is a functional group less than or equal to 100000 daltons), (CH 2 )nCO 2 R16 (where RI6 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted 15 aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n=l, 2, 3, 4),

(CH

2 )nCONHR16, (CH,)nCON(R16)2,

CO

2 R16, CONHRI6, CONR16R16, SR16 (where R16 is a functional group less than or equal to 100000 daltons), SO 3 H, SO 3 R16,

SO

2 NHR16, SO 2 N(RI6) 2 , SO 2 N(R16) 3 X - (where R16 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion), protein or biomolecule or 20 functional group less than or equal to 100000 daltons; Z is halide, acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, protein or biomolecule or functional group less than or equal to 100000 daltons.

WO 00/00204 PCT/US98/13601 104 Still another family of compounds has the following structure: R4 R3 R1 R5 R13 /\1 RI4 M \ R12 N N R7 / R11 R8 R9 RIO where each of R1-R14 can be CH 2

CH

3 , CH=CH2, CH=CHCH 2 N(CH3)2, 5 CH=CHCH2 N+(CH3)3 X (where X is a charge balancing ion), C(X) 2

C(X)

3 (where X is a halogen), CHO, COCH 3 , COH,

CO

2 R15, CONHR15, CH=CHCHO.

CH

2 Y, (where Y = H, halogen, OH, OR15 or is a functional group less than or equal to 100000 daltons), CH2CO2R15,

CH

2 CONHR15, CH=CHCH 2 OH, CH=CHCH 2 ORI5, CH(OH)CH 3 , CH(OR15)CH3, H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, o10 substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, NR15R15, CN, O, S, NHR15, OH, OR15, CHO, (CH 2 )nOH, (CH 2 )nSH, (CH2)nO-alkoxy,

(CH

2 )nSR15, (CH,)nOR15 (where n = 1, 2, 3, 4, and R15 is a functional group less than or equal to 100000 daltons), (CHz)nCOzR15 (where R15 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted 15 alkynyl, and n=1, 2, 3, 4), (CH 2 )nCONHR15 ,

(CH

2 )nCON(R 1 5)2, CO 2 RI5, CONHR15, CONR15R15, SR15 (where R15 is a functional group less than or equal to 100000 daltons),

SO

3 H, SO 3 R15, SO 2 NHR16,

SO

2 N(R15)2,

SO

2 N(R15) 3 'X (where R15 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion), protein or biomolecule or functional group less than or equal to 100000 daltons; M is In13 20 In"' 15 or a mixture of In" 113 and In"115; Z is a halide, acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, protein or biomolecule or functional group less than or equal to 100000 daltons. M can also be Ag, Ce, Co, Cr, Cu, Dy, Er, Fe, Ga, Hf, Ho, La, Lu, Mo, Mg, Nd, Pb, Pr, Rh, Sb, Sc, Sm, Sn, Tb, Th, Ti, TI, Tm, U, V, Y, Yb or Zr, preferably Pd, Pt, Ga, Al, Ru, 25 Sn or Zn.

WO 00/00204 PCT/US98/13601 105 Still another family of compounds has the formula: R3 Rll R4 R2\ R5 RIO in R12 N N RI /, R6 R8 - R7 R9 Where In is In' 1 3, In" 5 , or a mixture of In'' 3 and In" 5, each of R1-R12 is CH 2

CH

3 , CH=CH_, CH=CHCH 2 N(CH3)2, CH=CHCH 2 N'(CH3)3 X- (where X is a charge balancing 5 ion), C(X) 2

C(X)

3 (where X is a halogen), CHO, COCH3, COH,

CO

2 R13, CONHR13, CH=CHCHO.

CH

2 Y. (where Y = H. halogen, OH. OR13 or is a functional group less than or equal to 100000 daltons), CH2CO2R13,

CH

2 CONHR13, CH=CHCH2OH, CH=CHCH 2 OR13, CH(OH)CH3, CH(OR13)CH3, H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, 10 amide, ester, NR13RI3, CN, 0, S, NHR13, OH, OR13, CHO,

(CH

2 )nOH, (CH,)nSH,

(CH

2 )nO-alkoxy, (CH2)nSR13,

(CH

2 )nOR13 (where n = 1, 2, 3, 4, and R13 is a functional group less than or equal to 100000 daltons),

(CH

2 )nCO 2

R

I

3 (where R13 is H. a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, and n=l1, 2, 3, 4), (CH 2 )nCONHR13, 15 (CH,)nCON(R13)2, CO 2 R13, CONHRI3, CONR13R13, SR13 (where R13 is a functional groups less than or equal to 100000 daltons),

SO

3 H, SO 3 R13, SO 2 NHR13,

SO

2 N(R13)2,

SO

2 N(R13) 3

X

- (where R13 is a functional groups less than or equal to 100000 daltons and X is a charge balancing ion), protein or biomolecule or functional group less than or equal to 100000 daltons; Z is halide, acetate, OH, alkyl, aryl, substituted aryl, alkenyl, 20 substituted alkenyl, alkynyl, substituted alkynyl, protein or biomolecule or functional groups less than or equal to 100000 daltons.

WO 00/00204 PCT/US98/13601 106 Two other families of compounds have the structures of Compound I and II, below: X Y X Y / R /3 / N N N N H R5 i 1 Compound II R2 3 R1 Compound I Compound wherein M is In , In or a mixture of In 3 and In" 5 R1, R2 and R3 can be the same or different, and each is CO 2 H, CO2R4, CONR4,

CH

3 Y', 5 CONR4R4,

NH

2 , N(R4)2, or N(R4) 3

+Z

, where Y' is halogen, OH, OR4, or a functional group having a molecular weight equal to or less than 100,000 daltons, R4 is a functional group having a molecular weight equal to or less than 100,000 daltons, and Z is a physiologically acceptable charge balancing ion. with the proviso that R4 is not a mono or di-carboxylic acid of an amino acid, to R5 is a methylene group or an ethylene group, X is H, vinyl, ethyl, acetyl or formyl, and Y is methyl or formyl. M can also be Ag, AI, Ce, Co, Cr, Cu, Dy. Er, Eu, Fe, Ga, Gd, Hf, Ho, In, La. Lu, Mn, Mo, Nd, Pb, Pd, Pr, Pt, Rh, Sb, Sc, Sm, Tb, Th, Ti, TI, Tm, U, V, Y, Yb or Zr, and preferably is 15 In, Pd, or Pt.

WO 00/00204 PCT/US98/13601 107 In still another aspect, the invention is a free base or a metal complex having the structure of one of Compounds III and IV, below: X Y X Y RICompound III wherein M is 2H or a metal cation, R 1, R2 and R3 can be the same or different, and each is CO2H, CO2R4, CONR4, CH3Y', 5 CONR4R4, NH2, N(R4)2, N(R4)3 +Z -, or CONHR6OR7 where R6 is a bivalent moiety composed of a number, n, of alkylene groups and (n minus 1) oxygens, each oxygen linking two alkylene groups through an ether linkage, CONHR6OR7 where R6 is a bivalent moiety composed of a number, n, of alkylene groups and (n minus 1) oxygens, each oxygen linking two alkylene groups through an io ether linkage, and R7 is alkyl, and Z is a physiologically acceptable charge balancing ion, with the proviso that there is at least one R6 group in the structure, X is H, vinyl, ethyl, acetyl or formyl, and Y is methyl or formyl. 15 In the foregoing definition, and elsewhere herein, the term "alkylene" means a bivalent radical derived from an alkane with the free valences on different carbon carbon atoms. i.e., -CnH2n-- WO 00/00204 PCT/US98/13 6 01 108 Preferably, M is Ag, AI, Ce, Co, Cr, Cu, Dy, Er, Eu, Fe, Ga, Gd, Hf, Ho, In, La, Lu, Mn, Mo, Nd, Pb, Pd, Pr, Pt, Rh, Sb, Sc, Sm, Sn, Tb, Th, Ti, TI, Tmin, U, V, Y, Yb, Zn or Zr, most desirably Zn, Sn, In' , In , a mixture of In" and Inl 5, Pd, or Pt. In still another aspect, the invention is a metal complex having the structure of 5 one of Compound V and VI, below: X Y X Y N N N N NN 'HH 'H %5O R2 3 0 R I I Compound V Compound VI wherein M is 2H, In1 3 in11 5 or a mixture of In11 3 and In" 5 , R1, R2 and R3 can be the same or different, and each is X is H, vinyl, ethyl, acetyl or formyl, and Y is methyl or formyl. 10 M can also be Ag, Al, Ce, Co, Cr, Cu, Dy, Er, Eu, Fe, Ga, Gd, Hf, Ho, In, La, Lu, Mn, Mo, Nd, Pb, Pd, Pr, Pt, Rh, Sb, Sc, Sm, Tb, Th, Ti, TI, Tm, U, V, Y, Yb or Zr, most desirably Pd, Pt, In' , In 15 or a mixture of In 1 3 and In 1 15. In the foregoing discussion of the invention and in the following claims, the term functional group having a molecular weight equal to or less than 100,000 daltons has been 15 used. This term refers to such groups as monoclonal antibodies, proteins, saccharides, oligomeric nucleosides, peptides and the like. The terms alkyl, alkenyl, alkynyl, substituted alkenyl, substituted alkynyl and aryl, when used herein and in the appended WO 00/00204 PCT/US98/13601 109 claims to refer to substituents, preferably mean groups having 1 to 10, 2 to 10, 2 to 10, 2 to 10, 2 to 10 and 6 to 10 carbons, respectively. It will be apparent that various changes and modifications can be made from the specific disclosure of the invention set forth herein without departing from the spirit and 5 scope thereof as defined in the following claims.

Claims (30)

1. A phototherapeutic compound composed of an atom of In"113 or of In" 1 5 complexed with the inner nitrogens of a pyrrolic core composed of at least two pyrroles whose pyrrole linking atoms may be carbon or nitrogen or combinations thereof, with the proviso that 5 fully unsaturated porphyrins having the structures: R3 R12 R4 R2 R5 RI1 M RIO I N RI I R6 R9 R8 R7 where R1, R2, R4 and R6 are methyl, R8, R10, R11 and R12 are hydrogen, and R7 and R8 are CH 2 CH 2 COR 13 (where R13 is a moiety which results from the removal of H from an amino acid) and RI e M RI M N N MMe O2 R 2 CO2 R 2 10 where R1 is CH(OR)Me, R is alkyl, R2 is a residue derived by removing H from an amino acid, and M is 2H, Ga, Zn, Pd, In or Sn are excluded.

2. A phototherapeutic compound as claimed in claim I wherein the core is a tetrapyrrolic core.

3. A phototherapeutic compound as claimed in claim 2 wherein the core is a dihydro or 15 tetrahydro tetrapyrrolic core.

4. A phototherapeutic compound as claimed in claim 3 which has a tetrapyrrolic core whose linking atoms are carbon. WO 00/00204 PCT/US98/13601 111

5. A phototherapeutic compound as claimed in claim 4 having the structure of one of Compound I and Compound II, below: X Y X Y wherein M is In 1 3 Z, In I" Z, or a mixture of In" 3Z and In 115 Z, R I, R2 and R3 can be the same or different, and each is CO2H, CO2R4, CONR4, CH3Y', CONR4R4, NHI, N(R4)2, 5 or N(R4)3 +Z , where Y' is halogen, OH, OR4, or a functional group having a molecular weight equal to or less than 100,000 daltons, R4 is a functional group having a molecular weight equal to or less than 100,000 daltons, R5 is a methylene group or an ethylene group, X is H, vinyl, ethyl, acetyl or formyl, to Y is methyl or formyl, and Z is a physiologically acceptable charge balancing ion..

6, A free base or a metal complex having the structure of one of Compound III and Compound IV, below: WO 00/00204 PCT/US98/13601 112 X Y X Y N~N N N' N H 5H 2 3 0 R Compound III Compound IV wherein M is 2H or a metal cation and, associated with the metal cation, a physiologically acceptable charge balancing ion, R1, R2 and R3 can be the same or different, and each is CO 2 H, CO 2 R4, CONR4, CH 3 Y', CONR4R4, NH 2 , N(R4) 2 , N(R4) 3 * Z , or CONHR6OR7 5 where R4 is an alkyl group, R6 is a bivalent moiety composed of a number, n, of alkylene groups and (n minus 1) oxygens, each oxygen linking two alkylene groups through an ether linkage and R7 is an alkylene group, X is H, vinyl, ethyl, acetyl or formyl, and Y is methyl or formyl 10 with the proviso that the molecule includes at least one R6 group,

7. A metal complex as claimed in claim 6 where M is Ag, Al, Ce, Co, Cr, Cu, Dy, Er, Eu, Fe, Ga, Gd, Hf, Ho, In, La, Lu, Mn, Mo, Nd, Pb, Pd, Pr, Pt, Rh, Sb, Sc, Sm, Sn, Tb, Th, Ti, Tl, Tm, U, V, Y, Yb, Zn or Zr.

8. A metal complex as claimed in claim 7 where M Zn, Sn, Pd,, Pt, In" , In 115 or a 15 mixture of In" 3 and In" 5 WO 00/00204 PCT/US98/13601 113

9. A phototherapeutic compound as claimed in claim 4 having the structure of one of Compound V and Compound VI, below: X Y X Y NN-.N N N N N H H 5 / R2 3 0 Ri I RCompound V Compound VI wherein M is 2H, In 13, In" 5 or a mixture of In 13 and In' 5 and, associated with the In ' 3 , In' 15 or mixture of In" 3 and In' 5, a physiologically acceptable charge balancing ion, 5 RI and R3 can be the same or different, and each is CO 2 CH 3 , COzH, CO 2 R4, or an amide, where R4 is an alkyl or a phenyl group, R2 is CO 2 CH, , CO 2 H, CO2R4, an amide, CH2COCH3, CH 2 CO 2 H, or CH2-,CO 2 R4, where R4 is an alkyl or a phenyl group, R5 is methylene or ethylene, 10 X is H, vinyl, ethyl, acetyl or formyl, and Y is methyl or formyl.

10. A phototherapeutic compound as claimed in claim 4 which has the structure: RI R5 SNN R3 M N N H H R4 X R2 WO 00/00204 PCT/US98/13601 114 where R I- R5 can be the same or different and each is CH 2 CH 3 , CH=CH 2 , CH=CHCH 2 N(CH 3 )2, CH=CHCH2 N + (CH3)3 X I-, C(Y 1) 2 C(Y 1)3, CHO, COCH 3 , CO 2 H, CO 2 R6, CONHR6, CH=CHCHO, CH 2 Y, CH=CHCH 2 OH, CH=CHCH20R6, CH(OH)CH3, CH(OR6)CH3, H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted 5 aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, NR6R6, CN, OH, OR6, (CH,)nOH, (CH,)nSH, (CH 2 )nO-alkoxy, (CH,)nSR6, (CH 2 )nOR6, (CH 2 )nCO 2 R6, (CH 1 )nCONHR6 , (CH,)nCON(R6)2, CO2R6, CONHR6, CONR6R6, SR6, SO 3 H, SO 3 R6, SO 2 NHR6, SOzN(R6) 2 , SO 2 N(R6) 3 +X I -; M is I-n 1 , In' 5 or a mixture of In" 3 and In 5; 10 Z is a halide , acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, protein or biomolecule or functional group less than or equal to 100000 daltons; Y1 is halogen;. Y is H, halogen, OH, OR6 or is a functional group less than or equal to 100000 daltons; 15 R6 is a functional group less than or equal to 100000 daltons; R7 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl; Xl is a charge balancing ion; and X is O, 2H, (H, OH), S, (H, OR6) or a ketone protecting group. 20

11. A phototherapeutic compound as claimed in claim 10 wherein: R1 is CH=CH 2 , CHO, Et, COCH 3 R2 is CO 2 CH 3 ,CO 2 H, or an amide R3 and R4 are H R5 is CH 3 25 XisO M is In" 3, In"' 15 or a mixture of In" 3 and In" 15 WO 00/00204 PCT/US98/13601 115 Z is a halide, acetate or OH.

12. A phototherapeutic compound as claimed in claim 4 which has the structure: 5 R3 R4 R5 R6 /C. D XA B R2-B C-R7 ~N \,I I A D A' Z R8 RI N N R176 N N R9 B A ,D C N I R1 6 -C B- A, ,D c B-RIO R15 RI4 RI3 R11 where each of R1-R17 is H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl. substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, C(X) 2 C(X) 3 (where X is a halogen), NR18RI8, CN, OH, OR18, CHO, COCH 3 , (CH 2 )nOH, (CH,)nSH, 10 CH(OR18)CH 3 , (CH 2 )nO-alkoxy, (CH 2 )nSR18, (CH2)nOR18(where n = 1, 2, 3, 4, and R5 is a functional groups less than or equal to 100000 daltons), (CH2)nCO, 2 R18 (where R18 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl or substituted alkynyl, and n=l, 2, 3, 4), (CH 2 )nCONHR18, (CH 2 )nCON(Rl8) 2 , CO 2 RI8, CONHR18, CONR18RI8, SR18 (where R18 is a functional 15 group less than or equal to 100000 daltons). SO 3 X, SO 3 R18, SO 2 NHR18. SO 2 N(R18) 2 , SO 2 N(R18) 3 +X- (where R18 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion); A, B, C and D are; C, N, 0 + , O, S, Te, P, N+(R19)X (where RI9 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion), or combinations thereof; M is In'' 3 , In" 5 or a mixture of In 11 3 and In ll5 ; Z is a 20 halide, acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, a protein or biomolecule or functional group less than or equal to 100000 daltons. WO 00/00204 PCT/US98/13601 116

13. A phototherapeutic compound as claimed in claim 4 which has the structure: R4 15 R8 R9 R3-B R6 R7 C-RIO EA F D R2 F E \ RI2 R, jN R12 N M AN N N\ R24 N N R13 R23 'E .- / E RE N,_& / /. // F\ ,F R22-C A RI9 RI8 / B-R15 B A N D C R21 R20 RI7 RI16 R21I 5 were each of R1-R24 is H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, C(X) 2 C(X) 3 (where X is a halogen), NR25R25, CN, OH, OR25, CHO, COCH 3 , (CH 2 )nOH, (CH 2 )nSH, CH(OR25)CH3, (CH,)nO-alkoxy, (CH 2 )nSR25, (CH 2 )nOR25 (where n = 1, 2, 3, 4, and io R25 is a functional group less than or equal to 100000 daltons), (CH 2 )nCO 2 R25 (where R25 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl. substituted aryl, alkenyl, substituted alkenyl, alkynyl or substituted alkynyl, and n=1, 2, 3, 4), (CH 2 )nCONHR25, (CH,)nCON(R25)2, CO2R25, CONHR25, CONR25R25, SR25 (where R25 is a functional group less than or equal to 100000 daltons), SO 3 H, SO 3 R25, 15 SO 2 NHR25, SO 2 N(R25)2, SO 2 N(R25) 3 +X - (where R25 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion); M is In i 3 , In 1 1 5 or a mixture of In" 13 and In" 115 ; A, B, C, D, E, F are; C, N, O0, O, S, Te, P, N+(R25)X - (where R25 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion), or combinations thereof; Z is a halide , acetate. OH. alkyl, aryl, substituted aryl, alkenyl, 20 substituted alkenyl, alkynyl, substituted alkynyl, or a protein or biomolecule or functional group less than or equal to 100000 daltons. WO 00/00204 PCT/US98/13601 117

14. A phototherapeutic compound as claimed in claim 4 which has the structure: RI R2 R5 R4 R3 R6 N NZ N R7 M / R13 N N R8 / RI2 R9 RIO Rll 5 where each RI-R13 is H, halide, alkyl, vinyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, CH=CHCH 2 N(CH 3 ) 2 , CH=CHCH 2 N+(CH 3 ) 3 X (where X is a charge balancing ion), C(X) 2 C(X) 3 (where X is a halogen), NR14RI4, CN, OH, OR14, CHO, COCH 3 , (CH,)nOH, (CH,)nSH, (CH,)nO-alkoxy, CH(OH)CH 3 , CH(OR14)CH 3 (CH 2 )nSR14, 10 (CH,)nOR14 (where n = 1, 2. 3. 4, and R1I4 is a functional groups less than or equal to 100000 daltons), (CH 2 )nCOR14 (where R14 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n=1, 2, 3, 4), (CH,)nCONHR14, (CH 2 )nCON(RI4) 2 , CO2R14, CONHR14, CONR14RI4, SR14 (where R14 is a functional group less than or equal to 100000 15 daltons), SO3X, SO 3 R14, SO2R14, SO 2 NHR14, SO 2 N(RI4) 2 , SO 2 N(RI4) 3 +X - (where R14 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion); M is In 11 3, In 115 or a mixture of In l 3 and In ' 5 ; Z is a halide , acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, a protein or biomolecule or functional group less than or equal to 100000 daltons. 20 WO 00/00204 PCT/US98/13601 118

15. A phototherapeutic compound as claimed in claim 4 which has the structure: R2 RI R5 R 4 R3 R6 N ZN R7 M / R13 N N R / R12 R9 RIO R11 5 where each of Rl-R13 is H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, CH=CHCH 2 N(CH 3 ) 2 , CH=CHCH 2 N+(CH 3 ) 3 X (where X is a charge balancing ion), C(X) 2 C(X) 3 (where X is a halogen), NR14R14. CN, OH, OR14, CHO, (CH 2 )nOH, (CH,)nSH, (CH 2 )nO-alkoxy, CH(OH)CH 3 , CH(OR14)CH 3 (CH 2 )nSR14, (CH 2 )nOR14 10 (where n = 1, 2, 3, 4, and R14 is a functional groups less than or equal to 100000 daltons), (CH,)nCO2R14 (where RI4 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n= 1, 2, 3, 4), (CH,)nCONHR14, (CH,),CONH(R14) 2 , CO2R14, CONHR14, CONR14R14, SRI4 (where R14 is a functional group less than or equal to 100000 daltons), SO 3 H. 15 SO 3 R14, SO2NHRI4, SO 2 N(R14) 2 , SO 2 N(R14) 3 + X (where R14 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion); M is In" 3 , In" or a mixture of In" 3 and In' 15; Z is a halide , acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, protein or biomolecule or functional group less than or equal to 100000 daltons. WO 00/00204 PCT/US98/13601 119

16. A phototherapeutic compound as claimed in claim 4 which has the structure: RI R2 R5 R4 R3 R6 'N Z N R7 M R 13 N N R8-- / R12 R9 RIO Rll 5 where each of RI and R2 is CO 2 R14 (where R14 is alkyl or aryl), CO2H (or a salt therof), SO 2 Ph, CN or combinations thereof; Each of R3, R6, R8, RI2 is Me. R5 is CH=CH 2 , or CH(OR14)CH 3 (where R14 is alkyl or aryl) Each of R4, R7, R13, R10 is H o10 R9 and R 11 are CH 2 CH 2 CO 2 R15 (where R15 is alkyl or H or a salt of the carboxylic acid). M is In"' , In" 5 or a mixture of In" 11 3 and In 1 5 Z is a halide, acetate, or OH.

17. A phototherapeutic compound as claimed in claim 4 which has the structure: 15 B-C" D B' D I II A E,,. \z B=A N, N A=B C, /\,, M / - ,C D-E N N E-D E A I II D , B where each of A, B, C, D and E is C, N, N'R (where R is alkyl charged or uncharged) or 20 combinations thereof; M is In 1, In 15 or a mixture of In" 113 and In"' 15 and WO 00/00204 PCT/US98/13601 120 Z is a halide, acetate, OH.

18. A phototherapeutic compound as claimed in claim 4 which has the structure: 5 R2 RI~ N 10/ M / N N R3 15 R4 where each of RI through R4 is SO 3 H (or a salt thereof), SO 2 NHR5, CO 2 H (or a salt thereof ), CONHR5, OH, OR5 (wherein R5 is an alcohol or ether containing group), 20 amide, N(CH 3 ) 2 , N(Et) 2 . M is In 13 , In' 15 or a mixture of In" 13 and In"' Z is a halide, acetate, OH.

19. A phototherapeutic compound as claimed in claim 4 which has the structure: 25 R2 RIO R3 RI ~R4 N Z N R9 ,M R1 R8 N N R85 -- * / R5 R7 .- R6 RI4 R12 R13 where each of R1-R14 is H, halide, methyl, ethyl, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, 30 C(X) 2 C(X) 3 (where X is a halogen), NR15RI5, CN, OH, OR15, CHO, COCH3, CH(OR15)CH3, (CH 2 )nOH, (CH 2 )nSH, (CH 2 )nO-alkoxy, (CH 2 )nSR15, (CH 2 )nOR15 WO 00/00204 PCT/US98/13601 121 (where n = 1, 2, 3, 4, and R15 is a functional groups less than or equal to 100000 daltons), (CH 2 )nCO 2 R15 (where R14 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkyne and n= 1, 2, 3, 4), (CH 2 )nCONHR15, (CH,)nCON(R15),, CO2R15, CONHR15, CONRI5R15, SR15 (where 5 R15 is a functional groups less than or equal to 100000 daltons and n=l, 2, 3, 4), SOH, S0 3 R15, SO 2 NHR15, SO 2 N(R15) 2 , SO 3 N(RI5) 3 +X - (where RI5 is a functional groups less than or equal to 100000 daltons and X is a charge balancing ion); M is In 3, In' 15 or a mixture of In' 3 and In" 15 Z is a halide , acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, or a functional group less than or equal to 10 100000 daltons, a protein or a biomolecule.

20. A phototherapeutic compound as claimed in claim 4 which has the structure: R2 R3 RI R4 N Z N R8 N N \~ / R5 R7R6 R9 15 where each of R1-R8 is ethyl or methyl R9 is CH 3 , SO 2 NH(CHeCH 2 O)nCH 3 (n=1 to 1000), SO 2 N((CH 2 CH 2 O)nCH 3 ), (n=1 to 1000); SO 2 NH(CH 2 )nOH (n=l to 1000), CH3, SON((CH 2 CH 2 )nOH) 2 (n=l to 1000); SO 2 NC((N(CH,) 2 )2 ; SO 2 NH(CH 2 )nN(CH 3 ) 2 (n=1 to 1000); SO,NH(CH,)nSH (n=1 to 20 1000); SO 2 NHC(CH 2 CH2OH) 3 ; SO 2 NHCH 2 CO 2 H (or salts thereof); SO 2 NH(CH 2 )nCH(NH 2 )CO 2 H (or salts therof) (n=1 to 5); SO 2 NHCH 2 CO 2 R10 (RO10 is alkyl, aryl); SO 2 NH(CH 2 )nCH(NH 2 )CO 2 R1 0 (RO10 is alkyl, aryl) (n=1 to 5) M is In" 3 , In' 15 or a mixture of In" 3 and In' 5 Z is a halide, acetate, OH. WO 00/00204 PCT/US98/13601 122

21. A phototherapeutic compound as claimed in claim 4 which has the structure: R2 R3 RI R4 5 -N Z N R8 N N S / R5 10 R R6 R where each of R1-R8 is ethyl or methyl. R9 is; CH 2 CONH(CHCHzO)nCH 3 (n = 1 to 1000), CHzCO 2 N((CH 2 CH 2 O)nCH 3 ) 2 (n=l to 1000); CH2CO 2 NH(CHz),OH (n=l to 1000), CHzCO 2 N((CH 2 CH 2 )nOH) 2 (n=l to 1000); 15 CH,CONC((N(CH 3 ) 2 ), ; CHzCO 2 NH(CH 2 )nN(CH 3 ) 2 (n=1 to 1000); CH 2 CO 2 N(CH,)nSH (n=1 to 1000); CH 2 CONHC(CH 2 CH 2 OH) 3 ; CH 2 CO 2 NHCH 2 CO 2 H (or salts thereof); CH 2 CONH(CHz)nCH(NH 2 )CO 2 H (or salts thereof) (n=l to 5); CHCOzNHCH,CO 2 R10 (R10 is alkyl, aryl); CHzCOzNH(CH 2 )nCH(NH,)CO 2 R10 (R10 is alkyl, aryl) (n=1 to 5) M is In 1 13, In 115 or a mixture of In l 3 and Ini 1 5 20 Z is a halide , acetate, OH.

22. A phototherapeutic compound as claimed in claim 4 which has the structure: R3 R11 R4 R2 \ " -R5 R10O-A M C-R12 N N RI R6 R9 R7 RI4 R13 R8 where each of R1-R14 is H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, 25 alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, CH=CHCH 2 N(CH 3 ) 2 , CH=CHCH 2 N+(CH 3 ) 3 X (where X is a charge balancing ion), C(X) 2 C(X) 3 (where X is a halogen), NR15R15, CN, OH, OR15, CHO, (CH 2 ).OH, (CH,)nSH. (CH,)nO-alkoxy, CH(OH)CH 3 , CH(OR15)CH 3 (CH,)nSR15, (CH 2 )nOR15 WO 00/00204 PCT/US98/13601 123 (where n = 1, 2, 3, 4, and R15 is a functional groups less than or equal to 100000 daltons), (CH,)nCOzR15 (where R15 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkyne and n=l, 2, 3, 4), (CH 2 ),CONHR15. (CH,)nCON(R15) 2 , CO2R15, CONHRI5, CONR15RI5, SR15 (where 5 R15 is a functional groups less than or equal to 100000 daltons), SO 3 H, SO 3 R15, SO 2 NHR15, SO 2 N(R15) 2 , SO 2 N(RI5) 3 +X - (where R15 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion); A, B, C, D are; C, N, O', O, S, Te, P or combinations thereof; M is In l l3 , In 11 5 or a mixture of In 11 3 and In' 15 ; Z is a halide , acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, 10 substituted alkynyl, protein or biomolecule or functional group less than or equal to 100000 daltons.

23. A phototherapeutic compound as claimed in claim 4 which has the structure: R3 R14 R4 R2~ Z R5 R12 \ /In R113 N N RI 7 \ R6 RI11 15 RIO R9 R8 R7 where each of R1 through R14 is H, halide, alkyl, cyclic alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alklynyl, amide, ester, C(X) 2 C(X) 3 (where X is a halogen), NRI5R15, CN, OH, OR15, CHO, COCH 3 , (CH 2 )nOH, 20 (CH 2 )nSH, (CH 2 )nO-alkoxy, (CH,)nSR15, (CH 2 )nOR15 (where n = 1, 2, 3, 4, and R15 is a functional group less than or equal to 100000 daltons), (CH 2 )nCO2R15 (where R15 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n=l, 2, 3, 4), (CH 2 )nCONHR15, (CH 2 )nCON(R15) 2 , CO2R15, CONHR15, CON(R15) 2 , (where R15 is a functional group 25 less than or equal to 100000 daltons), SR15 (where R15 is a functional group less than or equal to 100000 daltons), SO 3 H, SO 3 R15, SO 2 NHR15, SO 2 N(R15) 2 , SO 2 N(R15) 3 +X (where R15 is a functional groups less than or equal to 100000 daltons and X is a charge balancing ion); M is In" 3 , In' 5 or a mixture of In 113 and In' 5 ; Z is a halide, acetate, OH, WO 00/00204 PCT/US98/13601 124 alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl or substituted alkynyl, or a functional group less than or equal to 100000 daltons, protein or biomolecule.

24. A phototherapeutic compound as claimed in claim 4 which has the structure: R1 R4 R5 R6 Nj N R3 ,M H N N H H AX B R2 5 wherein; RI is CH=CH2, Et, CHO, or COCH 3 R4 is Me R3 is H o10 R2 is CO 2 CH 3 , CO 2 H, CO 2 R7 (R7 is an alkyl, phenyl), or an amide Each of A and B is O or NR5 ( R5 is alkyl). X is O or NR6 (R6 is alkyl, an amino acid, an alcohol containing group, or an ether containing group) M is In 1 3 , In'' 5 or a mixture of In' 3 and In 115 15 Z is a halide , acetate, or OH.

25. A phototherapeutic compound as claimed in claim 4 which has the structure: 20 R1 R5 R6 R6 R3 M / H N N H H R2 R4 X WO 00/00204 PCT/US98/13601 125 where each of R1- R6 is CH 2 CH 3 , CH=CH 2 , CH=CHCH 2 N(CH 3 ) 2 , CH=CHCH 2 N+(CH 3 ) 3 X (where X is a charge balancing ion), C(X) 2 C(X) 3 (where X is a halogen), CHO, 5 COCH 3 , CO2H, CO2R7, CONHR7, CH=CHCHO, CH 2 Y, (where Y = H, halogen, OH, OR7 or is a functional group less than or equal to 100000 daltons), CH 2 CO 2 R7, CH 2 CONHR7, CH=CHCH 2 OH, CH=CHCH 2 OR7, CH(OH)CH 3 , CH(OR7)CH 3 , H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, NR7R7, CN, O, S, NHR7, OH, OR7, CHO, o10 (CH 2 )nOH, (CH,)nSH, (CH,)nO-alkoxy, (CH,)nSR7, (CH,)nOR7 (where n = 1, 2, 3, 4, and R7 is a functional group less than or equal to 100000 daltons), (CH 2 )nCO 2 R7 (where R7 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl or substituted alkynyl, and n= 1, 2, 3, 4), (CH 2 )nCONR7, CO 2 R7, CONHR7, CONRIOR7, SR7 (where R7 is a functional group less than or equal to 15 100000 daltons), SO 3 H, SO 3 R7, SO 2 NHR7, SO 2 N(R7) 2 , SO 2 N(R7) 3 + X (where R7 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion), protein or biomolecule or functional group less than or equal to 100000 daltons; X is O, H 2 , (H, OH), (H, OR8) S, or a ketone protecting group; M is In" 3 In15 or a mixture of In" 3 3 and In 15; Z is a halide , acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted 20 alkenyl, alkynyl, substituted alkynyl, protein or biomolecule or functional group less than or equal to 100000 daltons.

26. A phototherapeutic compound as claimed in claim 4 which has the structure: R1 R5 R7 N Z N R3 / H N N H H R8 R4 R2 25 where each of R1- R8 is CH 2 CH 3 , CH=CH 2 , CH=CHCH 2 N(CH 3 )2, CH=CHCH 2 N'(CH 3 ) 3 X (where X is a charge balancing ion), C(X) 2 C(X) 3 (where X is a halogen), CHO, COCH 3 . CO2,H. CO2R9. CONHR9, CH=CHCHO, CH 2 Y, (where Y = H, halogen, OH, WO 00/00204 PCT/US98/13601 126 OR9 or is a functional group less than or equal to 100000 daltons), CH 2 CO 2 R9, CH 2 CONHR9, CH=CHCH 2 OH, CH=CHCH 2 OR9, CH(OH)CH 3 , CH(OR9)CH 3 , H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, NR9R9, CN, O, S, NHR9, OH, OR9, CHO, 5 (CH,)nOH, (CH,)nSH, (CH,)nO-alkoxy, (CH 2 )nSR9, (CH 2 )nOR9 (where n = 1, 2, 3, 4, and R9 is a functional group less than or equal to 100000 daltons), (CH 2 )nCO 2 R9 (where R9 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n=1, 2, 3, 4), (CH 2 )nCONHR9, (CH,)nCON(R9)2, CO2R9, CONHR9, CONR10R9, SR9 (where R9 is a functional group 10 less than or equal to 100000 daltons), SO 3 H, SO 3 R9, SO 2 NHR9, SO 2 N(R9) 2 , SO 2 N(R9) 3 +X - (where R9 is a functional group less than or equal to 100000 daltons and X is a charge balancing ion), protein or biomolecule or functional group less than or equal to 100000 daltons; M is In 1 3 , In I " 5 or a mixture of In' 3 and In i 5 ; Z is a halide , acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, a 15 protein or biomolecule or functional group less than or equal to 100000 daltons.

27. A phototherapeutic compound as claimed in claim 4 which has the structure: R1 R 5 R 7 RR7 \ , 20 wherein; R1 is CH=CH2, Et, CHO, or COCH3 R5 is O or NR9 (where R9 is alkyl) R7 is Me R3R3 is H 25 R4 and R8 are H, CO2CH3, CO2H (or a salt thereof), CO2RIO (RIO is an alkyl or phenyl group), an amide, CH2CO2_CH3, CHzCO2H (or a salt thereof), CO2R10 (R10 is an alkyl or Ha phenyl group), or an amide H R8 R4 R2 20 wherein; RI is CH=CH 2 , Et, CHO, or COCH 3 R5 is 0 or NR9 (where R9 is alkyl) R7 is Me R3is H 25 R4 and R8 are H, CO 2 CH 3 , CO 2 H (or a salt thereof), CO 2 RIO (RIO is an alkyl or phenyl group), an amide, CHCO2,CH 3 , CHCO 2 H (or a salt thereof), CO. 2 R1O (RIO is an alkyl or a phenyl group), or an amide WO 00/00204 PCT/US98/13601 127 R2 is CO 2 CH 3 , CO 2 H, CO 2 RI0 (R10 is an alkyl or phenyl group), or an amide M is In l 3 , In"' 15 or a mixture of In' 3 and In 1 5 Z is a halide , acetate, or OH.

28. A phototherapeutic compound as claimed in claim 4 which has the structure: 5 R1 R4 R5 R3 M / H N N H H A X B R2 where each of R1- R5 is CH 2 CH 3 , CH=CH 2 , CH=CHCH 2 N(CH 3 ) 2 , CH=CHCH 2 N+(CH 3 ) 3 X- (where X is a charge balancing ion), C(X) 2 C(X)3 (where X is a halogen), CHO, COCH 3 , CO 2 H, CO2R6, CONHR6, CH=CHCHO, CH 2 Y, (where Y = H, halogen, OH, 10 OR6 or is a functional group less than or equal to 100000 daltons), CH 2 CO 2 R6, CH 2 CONHR6, CH=CHCH20H, CH=CHCH 2 OR8, CH(OH)CH 3 , CH(OR6)CH 3 , H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, NR6R6, CN, O, S, NHR6, OH, OR6, CHO, (CH,)nOH, (CH2)nSH, (CH,)nO-alkoxy, (CH 2 )nSR6, (CH 2 )nOR6 (where n = 1, 2, 3, 4, and 15 R6 is a functional group less than or equal to 100000 daltons), (CH 2 )nCO 2 R6 (where R6 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n=l, 2, 3, 4), (CH 2 )nCONR6, CO 2 R6, CONHR6, CONR6R6, SR6 (where R6 is a functional group less than or equal to 100000 daltons), SO 3 H, SO 3 R6, SO 2 NHR6, SO 2 N(R6) 2 , SO 2 N(R6) 3 +X (where R6 is a 20 functional group less than or equal to 100000 daltons and X is a charge balancing ion), protein or biomolecule or functional group less than or equal to 100000 daltons: X is O, NR6 (where R6 is H, alkyl (1-10 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, an amino acid, an amino acid ester or a functional group less than or equal to 100000 daltons); A and B are O, NH, NR6 or combinations 25 thereof; Z is a halide , acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, protein or biomolecule or functional group less than or equal to 100000 daltons. WO 00/00204 PCT/US98/13601 128

29. A phototherapeutic compound as claimed in claim 4 which has the structure: RI R4 R =N, NC R5 iM H N N H H A X B R2 wherein: 5 Ri is CH=CH 2 , Et. CHO, or COCH 3 R4 is 0 or NR6 (where R6 is alkyl) R5 is MeR3 is H R2 is CO 2 CH 3 , CO 2 H, CO 2 R7 (R7 is an alkyl or phenyl group), or an amide X is O, NR6 (R6 is alkyl, an amino acid, an alcohol containing group, or an ether 10 containing group) M is In'' 3 , In 1 15 or a mixture of In i 1 3 and In" 5 Z is a halide , acetate, OH, and A and B are O or NR6 where R 6 is alkyl. 15

30. A phototherapeutic compound as claimed in claim 4 which has the structure: RI R5 R6 R3 ,M N N H H R2 R4 X where each of R1- R6 is CH 2 CH 3 , CH=CH 2 , CH=CHCH 2 N(CH 3 )2, CH=CHCH 2 N+(CH 3 ) 3 X- (where X is a charge balancing ion), C(X) 2 C(X) 3 (where X is a halogen), CHO, 20 COCH 3 , CO2H, CO2R7, CONHR7, CH=CHCHO, CH 2 Y, (where Y = H, halogen, OH, OR7 or is a functional group less than or equal to 100000 daltons), CH 2 CO 2 R7, WO 00/00204 PCT/US98/13601 129 CH 2 CONHR7, CH=CHCH 2 OH, CH=CHCH 2 OR7, CH(OH)CH 3 , CH(OR7)CH 3 , H, halide, alkyl, cyclic alkyl (3-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, amide, ester, NR7R7, CN, O, S, NHR7, OH, OR7, CHO, (CH,)nOH, (CH,)nSH, (CH,)nO-alkoxy, (CH 2 )nSR7, (CH 2 )nOR7 (where n = 1, 2, 3, 4, and 5 R7 is a functional group less than or equal to 100000 daltons), (CH 2 )nCO 2 R7 (where R7 is H, a physiologically acceptable salt, alkyl (1-6 carbons), aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl, and n=1, 2, 3, 4), (CH 2 )nCONR7, CO,R7, CONHR7, CONR7R7, SR7 (where R7 is a functional group less than or equal to 100000 daltons), SO 3 H, SO 3 R7, SO 2 NHR7, SO 2 N(R7) 2 , SO 2 N(R7) 3 'X - (where R7 is a 10 functional group less than or equal to 100000 daltons and X is a charge balancing ion), protein or biomolecule or functional group less than or equal to 100000 daltons; X is O, H2, (H, OH), (H, OR7), S, or a ketone protecting group; M is In l 3 , In11 5 or a mixture of In 13 and In' 15 ; Z is a halide , acetate, OH, alkyl, aryl, substituted aryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, protein or biomolecule or functional group less than 15 or equal to 100000 daltons.