CN115197260B - Alkynyl coupled double BODIPY near infrared fluorescent dye with J aggregation effect and preparation method thereof - Google Patents
Alkynyl coupled double BODIPY near infrared fluorescent dye with J aggregation effect and preparation method thereof Download PDFInfo
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- 125000000304 alkynyl group Chemical group 0.000 title claims abstract description 35
- 239000007850 fluorescent dye Substances 0.000 title claims abstract description 35
- 230000002776 aggregation Effects 0.000 title claims abstract description 30
- 238000004220 aggregation Methods 0.000 title claims abstract description 30
- 230000000694 effects Effects 0.000 title claims abstract description 30
- 238000002360 preparation method Methods 0.000 title abstract description 14
- 238000000862 absorption spectrum Methods 0.000 claims abstract description 13
- 239000012046 mixed solvent Substances 0.000 claims abstract description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 24
- 238000002189 fluorescence spectrum Methods 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 abstract description 29
- 239000000975 dye Substances 0.000 abstract description 17
- 239000002904 solvent Substances 0.000 abstract description 16
- 238000010521 absorption reaction Methods 0.000 abstract description 7
- 150000001875 compounds Chemical class 0.000 abstract description 7
- 230000021615 conjugation Effects 0.000 abstract description 3
- 238000000295 emission spectrum Methods 0.000 abstract description 3
- BSCHIACBONPEOB-UHFFFAOYSA-N oxolane;hydrate Chemical compound O.C1CCOC1 BSCHIACBONPEOB-UHFFFAOYSA-N 0.000 abstract description 3
- 238000009825 accumulation Methods 0.000 abstract description 2
- 125000005577 anthracene group Chemical group 0.000 abstract description 2
- 238000002428 photodynamic therapy Methods 0.000 abstract description 2
- 238000007669 thermal treatment Methods 0.000 abstract description 2
- 238000003477 Sonogashira cross-coupling reaction Methods 0.000 abstract 1
- 238000000799 fluorescence microscopy Methods 0.000 abstract 1
- 238000000746 purification Methods 0.000 abstract 1
- 238000000926 separation method Methods 0.000 abstract 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 48
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 32
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 24
- BFMYDTVEBKDAKJ-UHFFFAOYSA-L disodium;(2',7'-dibromo-3',6'-dioxido-3-oxospiro[2-benzofuran-1,9'-xanthene]-4'-yl)mercury;hydrate Chemical compound O.[Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC(Br)=C([O-])C([Hg])=C1OC1=C2C=C(Br)C([O-])=C1 BFMYDTVEBKDAKJ-UHFFFAOYSA-L 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 239000000243 solution Substances 0.000 description 12
- 239000003208 petroleum Substances 0.000 description 9
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 8
- LVTYICIALWPMFW-UHFFFAOYSA-N diisopropanolamine Chemical compound CC(O)CNCC(C)O LVTYICIALWPMFW-UHFFFAOYSA-N 0.000 description 8
- 229940043276 diisopropanolamine Drugs 0.000 description 8
- 238000001704 evaporation Methods 0.000 description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 7
- 239000003480 eluent Substances 0.000 description 7
- 239000011259 mixed solution Substances 0.000 description 7
- 238000010898 silica gel chromatography Methods 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 6
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 239000007806 chemical reaction intermediate Substances 0.000 description 4
- 239000007810 chemical reaction solvent Substances 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- 239000011550 stock solution Substances 0.000 description 4
- LMYRWZFENFIFIT-UHFFFAOYSA-N toluene-4-sulfonamide Chemical compound CC1=CC=C(S(N)(=O)=O)C=C1 LMYRWZFENFIFIT-UHFFFAOYSA-N 0.000 description 4
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- MNFZZNNFORDXSV-UHFFFAOYSA-N 4-(diethylamino)benzaldehyde Chemical compound CCN(CC)C1=CC=C(C=O)C=C1 MNFZZNNFORDXSV-UHFFFAOYSA-N 0.000 description 3
- 101150003085 Pdcl gene Proteins 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 238000005415 bioluminescence Methods 0.000 description 2
- 230000029918 bioluminescence Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 238000002059 diagnostic imaging Methods 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 238000006862 quantum yield reaction Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 102100027340 Slit homolog 2 protein Human genes 0.000 description 1
- 101710133576 Slit homolog 2 protein Proteins 0.000 description 1
- 150000003934 aromatic aldehydes Chemical class 0.000 description 1
- 239000000987 azo dye Substances 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 238000012984 biological imaging Methods 0.000 description 1
- 238000003889 chemical engineering Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- -1 etOH Chemical compound 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 238000001506 fluorescence spectroscopy Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000004768 lowest unoccupied molecular orbital Methods 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000005693 optoelectronics Effects 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000001007 phthalocyanine dye Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic System
- C07F5/02—Boron compounds
- C07F5/022—Boron compounds without C-boron linkages
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
- A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
- A61K49/0032—Methine dyes, e.g. cyanine dyes
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
- C09B23/00—Methine or polymethine dyes, e.g. cyanine dyes
- C09B23/14—Styryl dyes
- C09B23/145—Styryl dyes the ethylene chain carrying an heterocyclic residue, e.g. heterocycle-CH=CH-C6H5
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/645—Specially adapted constructive features of fluorimeters
- G01N21/6456—Spatial resolved fluorescence measurements; Imaging
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
- C09K2211/10—Non-macromolecular compounds
- C09K2211/1003—Carbocyclic compounds
- C09K2211/1007—Non-condensed systems
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
- C09K2211/10—Non-macromolecular compounds
- C09K2211/1003—Carbocyclic compounds
- C09K2211/1011—Condensed systems
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
- C09K2211/10—Non-macromolecular compounds
- C09K2211/1018—Heterocyclic compounds
- C09K2211/1025—Heterocyclic compounds characterised by ligands
- C09K2211/1044—Heterocyclic compounds characterised by ligands containing two nitrogen atoms as heteroatoms
- C09K2211/1055—Heterocyclic compounds characterised by ligands containing two nitrogen atoms as heteroatoms with other heteroatoms
Abstract
The invention relates to an alkynyl coupled double BODIPY near infrared fluorescent dye with J aggregation effect and a preparation method thereof, wherein an iodized BODIPY derivative (I) and an alkynyl BODIPY derivative (II) are used for obtaining a compound (III) through a Sonogashira coupling reaction. The preparation method has mild reaction conditions, better selectivity and simpler separation and purification. The conjugation degree of molecules is expanded through alkynyl conjugated bridging double BODIPY, so that absorption and emission spectrum red shift are promoted; simultaneously, an anthracene ring with larger steric hindrance and containing a condensed ring plane is introduced into a meso position, so that the steric conformation is increased and pi-pi accumulation among molecules is prevented to a certain extent; the dye has obvious solvent effect, and can form stable J aggregate when applied to a certain proportion of water-tetrahydrofuran mixed solvent, so that the absorption wavelength and the emission wavelength are further red shifted, and the dye has wide application prospect in the fields of near infrared biological fluorescence imaging, photo-thermal treatment, photodynamic treatment and the like.
Description
Technical Field
The invention belongs to the technical fields of organic compound synthesis, functional fluorescent dye and fine chemical engineering, and particularly relates to an alkynyl coupled double BODIPY near infrared fluorescent dye with a J aggregation effect and a preparation method thereof.
Background
The organism has stronger self-absorption and background scattering in the visible light region due to the self-characteristics, and if the maximum absorption of the dye is in the near infrared range, the background interference of the organism can be greatly reduced, and the sensitivity and the selectivity of the organism are improved, so that the near infrared fluorescent dye (with the absorption or emission wavelength of 650-1100 nm) becomes a star molecule in the current organic functional molecule field. Heretofore, near infrared dyes such as azo dyes, quinone dyes, phthalocyanine dyes and the like have been widely studied, but often require multi-step functional modification of the dyes to red shift the absorption thereof to the near infrared region, and the increase of molecular volume brings problems of reduced light stability, reduced fluorescence quantum yield, relative sensitivity to environment, poor biocompatibility and cell permeability and the like, which greatly limit the application and development of the dyes in the fields of optics, biology and medicine.
In recent years, intensive research into dye J aggregates has greatly expanded the application scenarios of dyes. The main feature of dye formation of J aggregates is their strong transition of absorption and emission spectra to lower energy (longer wavelength) relative to the monomer spectra, forming one-dimensional supramolecular self-organization. The appearance of J aggregate can enable the J aggregate to be red-shifted to a near infrared region through directional regulation and control by a small molecular dye relatively simply, so that the J aggregate has wide application prospects in the fields of photoreductant, chemical and biological sensing, biology and medical imaging.
Organic dyes are widely used in optoelectronic materials and biological monitoring because of their strong molar extinction coefficient and fluorescence quantum yield. Of these, BODIPY (BODIPY) is considered one of the more potential dyes in the field of bioluminescence imaging due to its higher photophysical properties, excellent photostability and chemical stability, good biocompatibility and stronger derivatization. BODIPY typically absorbs at about 500nm, and in recent years, the conjugated system is expanded by condensing different aromatic aldehydes with 3 and 5 positions of a BODIPY matrix, but the wavelength still hardly reaches more than 750 nm; and only through alkyne bond modification 2 and 6-site expansion conjugated structure, the absorption wavelength can only reach about 600nm, and the application of the modified conjugated structure in the biomedical field is limited.
The invention designs and synthesizes an alkynyl coupled double BODIPY near infrared fluorescent dye from an iodized BODIPY derivative. The preparation method of the compound is simple, the reaction condition is mild, and the operation is simple. The double BODIPY forms conjugation, a molecular conjugation system is prolonged, the molecules form rigid conjugated plane structures, the HOMO-LUMO energy level of the molecules is reduced, the spectrum of the red is promoted, and the optical performance of the molecules is improved. By regulating the J aggregation state of the molecules, the absorption and emission spectrum of the molecules is red shifted to 802nm, so that the molecules have great application potential in the fields of chemical and biological sensing, biological and medical imaging and the like.
Disclosure of Invention
The invention aims to: aiming at the defects existing in the prior art, the invention aims to provide an alkynyl coupled double BODIPY near infrared fluorescent dye with J aggregation effect and a preparation method thereof. It is another object of the present invention to apply it in tetrahydrofuran-water to form J aggregates.
The technical scheme is as follows: in order to achieve the aim of the invention, the invention adopts the following technical scheme:
the invention relates to an alkynyl coupled double BODIPY near infrared fluorescent dye with J aggregation effect and a preparation method thereof, and is characterized in that the near infrared fluorescent dye has a structural formula shown in a formula (III):
an alkynyl coupled double BODIPY near infrared fluorescent dye with J aggregation effect and a preparation method thereof, comprising the following steps:
1) Adding a compound (IV), 4-diethylaminobenzaldehyde and freshly dried p-toluenesulfonamide (PTSA) into a 100mL two-necked reaction flask under anhydrous condition, adding toluene and piperidine in a certain proportion, and heating the mixture to 140 ℃ for reflux for 6 hours; and (3) evaporating toluene to dryness, stopping the reaction, cooling to room temperature, dissolving dichloromethane, washing with water, drying, evaporating solvent under reduced pressure, separating and purifying by silica gel column chromatography, wherein the eluent is 70% dichloromethane-petroleum ether, and obtaining the iodized BODIPY derivative (I).
2) Dissolving iodinated BODIPY derivative (I) in a certain proportion of dry THF and Diisopropanolamine (DIPA), and under anhydrous and anaerobic condition, adding PdCl 2 (PPh 3 ) 2 And CuI were rapidly added to the reaction flask, and then Trimethylsilylacetylene (TMSA) was slowly added dropwise to the reaction system with a syringe, and reacted at 60 ℃ for 24 hours. Cooling to room temperature after the reaction is finished, evaporating the reaction solvent under reduced pressure, dissolving the residue with dichloromethane, washing the organic phase with water, and then passing through Na 2 SO 4 Drying and evaporating the organic solvent under reduced pressure. The eluent is 70% methylene dichloride-petroleum ether to obtain a reaction intermediate (V).
3) The reaction intermediate (V) was dissolved in dry THF, meOH and CH 2 Cl 2 Tetrabutylammonium fluoride (TBAF) was slowly added dropwise to the reaction flask under nitrogen atmosphere at 0℃and the reaction was kept under stirring in an ice bath for 1 hour. After the reaction is completed, the reaction solvent is distilled off under reduced pressure, and is separated and purified by silica gel column chromatography, and the eluent is 70 percent methylene dichloride-petroleum ether, thus obtaining the alkynyl BODIPY derivative (II).
4) Under the anhydrous and anaerobic condition, the iodized BODIPY derivative (I), the alkynyl BODIPY monomer derivative (II), the tetra (triphenylphosphine) palladium and the cuprous iodide are dissolved in a mixed solution of tetrahydrofuran and diisopropanolamine according to a certain proportion, and the temperature of a reaction system is raised to 70 ℃ for reaction for 16-18 hours; wherein the molar ratio of the BODIPY derivative (I), the BODIPY derivative (II), the tetra (triphenylphosphine) palladium and the cuprous iodide is 1:1-1.1:0.1:0.1; after the reaction is finished, the solvent is distilled off under reduced pressure, the residue is dissolved by methylene dichloride and washed by water for a plurality of times, an organic layer is separated, dried by anhydrous sodium sulfate, distilled off under reduced pressure, separated and purified by silica gel column chromatography, the eluent is 70% methylene dichloride-petroleum ether, and the obtained crude product is recrystallized by methylene dichloride/normal hexane to obtain the alkynyl coupled double BODIPY near infrared fluorescent dye (III) with J aggregation effect. The specific chemical reaction formula is as follows:
in the step 1), the amount ratio of the substances of the compound (IV), the 4-diethylaminobenzaldehyde and the PTSA is 4:16:1; the volume ratio of toluene to piperidine was 40:1.
In the step 2), the iodinated BODIPY derivatives (I) and PdCl 2 (PPh 3 ) 2 The ratio of the amounts of the substances CuI and TMSA is 1:0.1:0.1:3; the volume ratio of tetrahydrofuran to diisopropanolamine was 2:1.
In the step 3), the volume ratio of tetrahydrofuran, methanol and dichloromethane is 5:1:2.5.
In the step 4), the ratio of the amounts of the iodinated BODIPY derivative (I), the alkynyl BODIPY derivative (II), the tetrakis (triphenylphosphine) palladium and the cuprous iodide is 1:1 to 1.1:0.1:0.1. The volume ratio of tetrahydrofuran to diisopropanolamine was 2:1.
Advantageous effects of the invention
Compared with the prior art, the alkynyl coupled double BODIPY near infrared fluorescent dye with the J aggregation effect and the preparation method thereof have the advantages that: (1) Through alkynyl conjugated bridging, the steric hindrance between double BODIPY molecules is reduced, a molecular conjugated system is enlarged, the molecular energy gap is reduced, so that the spectrum is obviously red shifted, and the near infrared fluorescent dye molecule with the wavelength of more than 765nm is obtained; (2) The tetrahydrofuran-water mixed solvent system shows stable J aggregation effect, and the spectrum is red shifted; (3) An anthracene ring with larger steric hindrance and containing a condensed ring plane is introduced into a meso position, the steric hindrance is increased, meanwhile, the intermolecular pi-pi accumulation is also inhibited, the dye is promoted to form a stable J aggregate, the spectral performance of the organic dye is effectively regulated, and the application of the organic dye in the fields of bioluminescence imaging, photo-thermal treatment, photodynamic treatment and the like is facilitated.
Drawings
FIG. 1 is an ultraviolet-visible absorption spectrum of an alkynyl-coupled double BODIPY near infrared fluorescent dye (III) with J aggregation effect in different solvents;
FIG. 2 is a graph of fluorescence emission spectra of alkynyl-coupled double BODIPY near infrared fluorescent dyes (III) with J aggregation effect in different solvents;
FIG. 3 is a graph showing the ultraviolet-visible absorption spectrum of an alkynyl-coupled double BODIPY near infrared fluorescent dye (III) with J aggregation effect in THF/water mixed solutions with different proportions;
FIG. 4 is a graph showing fluorescence emission spectra of alkynyl-coupled double BODIPY near infrared fluorescent dyes (III) with J aggregation effect in THF/water mixed solutions with different ratios;
Detailed Description
The invention will be further described with reference to the accompanying drawings.
By using 1 The structure of the double BODIPY near infrared fluorescent dye with AIE effect is characterized and confirmed by H-NMR and MALDI-TOF-MS. The detection instrument comprises: bruker ARX400 type nuclear magnetic resonance apparatus, bruker ARX600 type nuclear magnetic resonance apparatus (using deuterated chloroform as solvent), shimadzu UV-3100 type ultraviolet-visible spectrophotometer (scanning range 300-900 nm, light path slit 2 nm), fluorescence spectrum using U.S. Amico Bowman Series 2 Luminescence Spectrometer test.
EXAMPLE 1 preparation of iodinated BODIPY derivatives (I)
BODIPY Compound (IV) (190 mg,0.36 mmol), 4-diethylaminobenzaldehyde (255 mg,1.44 mmol) and freshly dried PTSA (20 mg,0.10 mmol) were added to a 100mL two-necked reaction flask equipped with a Dean-Stark apparatus, followed by 20mL toluene and 0.5mL piperidine under anhydrous conditions, and the reaction was heated to 140℃under reflux for 6h; evaporating toluene to dryness, stopping the reaction, cooling to room temperature, dissolving dichloromethane, washing with water, drying, evaporating solvent under reduced pressure, separating and purifying by silica gel column chromatography, eluting with 70% dichloromethane-petroleum ether to obtain iodized BODIPY derivative (I) (260 mg, 86%). 1 H NMR(CDCl 3 ，400MHz，ppm)δ8.58(s，1H)，8.04-8.06(d，3H)，7.90-7.92(d，2H)，7.55-7.68(m，5H)，7.46-7.50(t，3H)，7.38-7.42(t，3H)，6.69(s，5H)，6.27(s，1H)，6.19-6.20(d，1H)，3.44(s，8H)，1.21-1.24(t，12H)。
EXAMPLE 2 preparation of alkynyl BODIPY derivatives (II)
The iodinated BODIPY monomer derivative (I) (250 mg,0.30 mmol) was dissolved in dry THF (10 mL) and DIPA (5 mL), and PdCl was dissolved under anhydrous and anaerobic conditions 2 (PPh 3 ) 2 (21 mg,10% mmol) and CuI (6 mg,10% mmol) were rapidly added to the reaction flask, followed by dropwise addition of TMSA (0.13 mL,0.90 mmol) to the reaction system with a syringe, and reaction at 60℃for 24 hours; cooling to room temperature after the reaction is finished, evaporating the reaction solvent under reduced pressure, dissolving the residue with dichloromethane, washing the organic phase with water, and thenNa 2 SO 4 Drying, and evaporating the solvent under reduced pressure; the crude product was purified by column chromatography on silica gel eluting with 70% dichloromethane-petroleum ether to give reaction intermediate (V) (214 mg, 88%). 1 HNMR(CDCl 3 ，600MHz，ppm)δ8.56(s，1H)，8.30-8.32(d，1H)，8.03-8.04(d，2H)，7.89-7.91(d，2H)，7.67(s，2H)，7.55-7.57(m，4H)，7.45-7.48(m，2H)，7.37-7.40(m，2H)，7.31(s，1H)，6.69-6.77(m，5H)，6.19(d，1H)，6.18(s，1H)，3.44(s，8H)，1.21-1.23(m，12H)，0.17(s，9H)。
The reaction intermediate (V) (230 mg,0.28 mmol) was dissolved in 10mL dry THF, 2mL MeOH and 5mL CH 2 Cl 2 To the reaction flask was slowly added dropwise TBAF (0.4 mL,1M in THF) in a nitrogen atmosphere at 0deg.C and the reaction was carried out with stirring in an ice bath for 1h; after the reaction is completed, the reaction solvent is distilled off under reduced pressure, the residue is separated and purified by silica gel column chromatography, and the eluent is 70% methylene dichloride-petroleum ether, so as to obtain an alkynyl BODIPY derivative (II) (200 mg, 97%). 1 H NMR(CDCl 3 ，600MHz，ppm)δ8.57(s，1H)，8.22-8.24(d，1H)，8.03-8.05(d，2H)，7.90-7.92(d，2H)，7.65-7.67(d，2H)，7.56-7.57(d，4H)，7.46-7.48(t，2H)，7.38-7.40(m，2H)，7.30-7.33(d，1H)，6.78(s，1H)，6.69-6.70(d，4H)，6.20(s，2H)，3.43(s，8H)，3.23(s，1H)，1.23-1.24(t，6H)，1.21-1.22(t，6H)。
Example 3 preparation of alkynyl-coupled double BODIPY near infrared fluorescent dye (III) with J aggregation effect
BODIPY derivative (I) (60 mg,0.07 mmol), BODIPY derivative (II) (60 mg,0.08 mmol), pd (PPh) under anhydrous conditions 3 ) 4 (8 mg,0.008 mmol) and CuI (2 mg,0.008 mmol) were dissolved in a mixed solution of tetrahydrofuran and diisopropanolamine (v/v, 10mL/5 mL), the reaction system was warmed to 70℃for 18 hours, the solvent was distilled off under reduced pressure after the completion of the reaction, the residue was dissolved in methylene chloride, washed with water several times, the organic layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and then separated and purified by silica gel column chromatography with an eluent of 70% methylene chloride-petroleum ether to give the compound (41 mg, 40%). 1 H NMR(CDCl 3 ，600MHz，ppm)δ8.56-8.58(d，2H)，8.30-8.33(d，1H)，8.03-8.06(t，4H)，7.90-7.92(m，4H)，7.64-7.70(m，4H)，7.55-7.61(m，9H)，7.45-7.48(t，4H)，7.37-7.41(m，5H)，7.29-7.33(m，2H)，6.77-6.79(d，2H)，6.69-6.72(t，8H)，6.19(d，2H)，6.18(s，1H)，3.43-3.44(d，16H)，1.21-1.24(t，24H)。
Example 4 preparation of alkynyl-coupled double BODIPY near infrared fluorescent dye (III) with J aggregation effect
BODIPY derivative (I) (50 mg,0.06 mmol), BODIPY derivative (II) (48 mg,0.07 mmol), pd (PPh) 3 ) 4 (7 mg, 0.0070 mmol) and CuI (2 mg,0.008 mmol) were dissolved in a mixed solution of tetrahydrofuran and diisopropanolamine (v/v, 10mL/5 mL), the reaction system was warmed to 70℃for 18 hours, the solvent was distilled off under reduced pressure after the completion of the reaction, the residue was dissolved in methylene chloride, washed with water several times, the organic layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and then separated and purified by silica gel column chromatography with an eluent of 70% methylene chloride-petroleum ether to give the compound (21 mg, 25%).
Example 5 ultraviolet-visible absorption Spectrum of alkynyl-coupled double BODIPY near infrared fluorescent dye (III) solution with J aggregation Effect
The alkynyl coupled double BODIPY near infrared fluorescent dye (III) with J aggregation effect is dissolved in five solvents (dichloromethane (DCM), tetrahydrofuran (THF), ethanol (EtOH), 1, 4-dioxane (Diox) and dimethyl sulfoxide (DMSO)) with different polarities to prepare the dye with concentration of 1 multiplied by 10 -5 The UV-visible absorption spectrum of the solution was measured in mol/L. FIG. 1 shows the UV-visible absorption spectrum of the fluorochrome (III) solution prepared in example 1 of the present invention.
Example 6 fluorescence emission Spectrum of alkynyl-coupled double BODIPY near infrared fluorescent dye (III) solution with J aggregation effect
Dissolving alkynyl coupled double BODIPY near infrared fluorescent dye (III) with J aggregation effect in five solvents (DCM, THF, etOH, diox, DMSO) with different polarities to obtain a concentration of 1×10 -5 The fluorescence emission spectrum of the solution of mol/L was measured. FIG. 2 is a fluorescence spectrum of the fluorescent dye (III) solution prepared in example 1 of the present invention.
EXAMPLE 7 ultraviolet-visible absorption Spectrum of alkynyl-coupled double BODIPY near-infrared fluorescent dye (III) with J aggregation Effect in different proportions of THF/Water Mixed solutions
Dissolving alkynyl coupled double BODIPY near infrared fluorescent dye (III) with J aggregation effect in THF to obtain a concentration of 1×10 -3 A mol/L stock solution. 7 parts of a 30. Mu.L stock solution were taken and diluted to 3mL with THF/water solutions of different ratios, respectively. Wherein the distilled water content is 0%, 10%, 20%, 30%, 60%, 90%, 99%, respectively; the ultraviolet-visible absorption spectra of the solutions were measured separately. From fig. 3, it can be seen that the electron absorption spectrum red-shifts with increasing water content in the solvent system, reaching a red-shift maximum when the water volume fraction is 99%, and the maximum absorption wavelength red-shifts from 765nm to 802nm of pure THF; FIG. 3 shows the UV-visible absorption spectrum of the solutions of the fluorescent dye (III) prepared in example 1 according to the invention in solution systems of different water contents.
Example 8 fluorescence emission Spectroscopy of alkynyl-coupled double BODIPY near infrared fluorescent dye (III) with J aggregation Effect in different ratios of THF/Water Mixed solutions
Dissolving alkynyl coupled double BODIPY near infrared fluorescent dye (III) with J aggregation effect in THF to obtain a concentration of 1×10 -3 A mol/L stock solution. 5 parts of 40. Mu.L stock solution were taken and diluted to 4mL with THF/water solutions of different ratios, respectively. Wherein the distilled water content is 0%, 5%, 10%, 20%, 30% respectively; respectively measuring fluorescence emission spectrograms of the fluorescent emission spectrograms; from fig. 4, it can be seen that the fluorescence emission spectrum red-shifted with increasing water content in the solvent system, reaching a red-shifted maximum when the water volume fraction is 30%, from 821nm to 829nm in pure THF; FIG. 4 is a graph showing fluorescence emission spectra of the fluorescent dye (III) prepared in example 1 under different water content of the solution system.
Claims (1)
1. The application of the alkynyl-coupled double-BODIPY near-infrared fluorescent dye (III) with the J aggregation effect is characterized in that the structural formula of the alkynyl-coupled double-BODIPY near-infrared fluorescent dye (III) with the J aggregation effect is shown as the formula (III):
the alkynyl coupled double BODIPY near infrared fluorescent dye (III) with the J aggregation effect is applied to a mixed solvent of water and THF to form stable J aggregation, and the absorption spectrum and the fluorescence emission spectrum are red shifted to more than 802nm through the J aggregation.
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| CN113150017A (en) * | 2021-02-02 | 2021-07-23 | 南京林业大学 | Coupled double-BODIPY near-infrared absorption dye and preparation method thereof |
| CN114230596A (en) * | 2021-12-28 | 2022-03-25 | 南京林业大学 | Preparation method of ethylene-bridged boron-fluorine pyrrole aggregate with absorption of more than 1200nm and photo-thermal diagnosis and treatment application thereof |
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| CN113150017A (en) * | 2021-02-02 | 2021-07-23 | 南京林业大学 | Coupled double-BODIPY near-infrared absorption dye and preparation method thereof |
| CN114230596A (en) * | 2021-12-28 | 2022-03-25 | 南京林业大学 | Preparation method of ethylene-bridged boron-fluorine pyrrole aggregate with absorption of more than 1200nm and photo-thermal diagnosis and treatment application thereof |
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