CN114656502A - Water-soluble aggregation-induced emission photosensitizer and preparation method thereof - Google Patents
Water-soluble aggregation-induced emission photosensitizer and preparation method thereof Download PDFInfo
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- 238000004220 aggregation Methods 0.000 title claims abstract description 34
- 230000002776 aggregation Effects 0.000 title claims abstract description 34
- 238000002360 preparation method Methods 0.000 title abstract description 8
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- 238000006243 chemical reaction Methods 0.000 claims description 31
- 239000000543 intermediate Substances 0.000 claims description 30
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 18
- 239000007787 solid Substances 0.000 claims description 18
- 239000002904 solvent Substances 0.000 claims description 15
- 238000002390 rotary evaporation Methods 0.000 claims description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 12
- 238000003756 stirring Methods 0.000 claims description 12
- 238000001816 cooling Methods 0.000 claims description 11
- 238000003786 synthesis reaction Methods 0.000 claims description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- 230000015572 biosynthetic process Effects 0.000 claims description 9
- 239000012295 chemical reaction liquid Substances 0.000 claims description 9
- 238000010992 reflux Methods 0.000 claims description 9
- 239000011259 mixed solution Substances 0.000 claims description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 7
- MUDSDYNRBDKLGK-UHFFFAOYSA-N 4-methylquinoline Chemical compound C1=CC=C2C(C)=CC=NC2=C1 MUDSDYNRBDKLGK-UHFFFAOYSA-N 0.000 claims description 6
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 claims description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 6
- DMBHHRLKUKUOEG-UHFFFAOYSA-N diphenylamine Chemical compound C=1C=CC=CC=1NC1=CC=CC=C1 DMBHHRLKUKUOEG-UHFFFAOYSA-N 0.000 claims description 6
- 238000010438 heat treatment Methods 0.000 claims description 6
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 6
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 6
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 5
- 238000001914 filtration Methods 0.000 claims description 5
- 230000002194 synthesizing effect Effects 0.000 claims description 5
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 3
- RDSIMGKJEYNNLF-UHFFFAOYSA-N 5-bromo-1-benzothiophene Chemical compound BrC1=CC=C2SC=CC2=C1 RDSIMGKJEYNNLF-UHFFFAOYSA-N 0.000 claims description 3
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 claims description 3
- 238000004440 column chromatography Methods 0.000 claims description 3
- 229940125904 compound 1 Drugs 0.000 claims description 3
- 230000007935 neutral effect Effects 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 238000010898 silica gel chromatography Methods 0.000 claims description 3
- WMKGGPCROCCUDY-UHFFFAOYSA-N 1,5-diphenylpenta-1,4-dien-3-one Chemical compound C=1C=CC=CC=1C=CC(=O)C=CC1=CC=CC=C1 WMKGGPCROCCUDY-UHFFFAOYSA-N 0.000 claims description 2
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- 230000001939 inductive effect Effects 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 abstract description 22
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 abstract description 7
- 239000007864 aqueous solution Substances 0.000 abstract description 6
- 238000006862 quantum yield reaction Methods 0.000 abstract description 3
- 210000004881 tumor cell Anatomy 0.000 description 12
- 238000002428 photodynamic therapy Methods 0.000 description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 229910052760 oxygen Inorganic materials 0.000 description 9
- 239000001301 oxygen Substances 0.000 description 9
- 101100377855 Artemia franciscana ABDA gene Proteins 0.000 description 6
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- 238000012360 testing method Methods 0.000 description 6
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- 238000009825 accumulation Methods 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
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- -1 i.e. Substances 0.000 description 2
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- 230000000171 quenching effect Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 206010034133 Pathogen resistance Diseases 0.000 description 1
- 206010034972 Photosensitivity reaction Diseases 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000021715 photosynthesis, light harvesting Effects 0.000 description 1
- 208000007578 phototoxic dermatitis Diseases 0.000 description 1
- 231100000018 phototoxicity Toxicity 0.000 description 1
- 231100000119 phototoxicity / photoirritation testing Toxicity 0.000 description 1
- 150000004032 porphyrins Chemical class 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000003642 reactive oxygen metabolite Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- ANRHNWWPFJCPAZ-UHFFFAOYSA-M thionine Chemical class [Cl-].C1=CC(N)=CC2=[S+]C3=CC(N)=CC=C3N=C21 ANRHNWWPFJCPAZ-UHFFFAOYSA-M 0.000 description 1
- 231100000820 toxicity test Toxicity 0.000 description 1
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
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Abstract
The invention relates to a water-soluble aggregation-induced emission photosensitizer and a preparation method thereof, which are characterized by the photophysical and photochemical properties of LOCK-0, LOCK-1 and LOCK-2 in a solution. The aggregation-induced emission photosensitizer has good water solubility, almost does not emit light in an aqueous solution, can emit light strongly in a tetrahydrofuran/water (THF fraction 99%) solution, and shows typical aggregation-induced emission properties, wherein the fluorescence quantum yield of LOCK-2 in the tetrahydrofuran/water (THF fraction 99%) solution is 56.8%, which is obviously higher than that of LOCK-0 (1.2%) and LOCK-1 (1.9%), and is also higher than that of most reported aggregation-induced emission photosensitizers.
Description
Technical Field
The invention relates to the fields of organic synthesis, biology and medicine, in particular to aggregation-induced emission organic salt and preparation and application thereof.
Background
Photodynamic therapy (PDT) is a highly effective and controllable treatment based on the principle that Photosensitizers (PS) react with oxygen or other substrates under light excitation to form reactive oxygen speciesAnd (3) a substance (ROS) which generates reactive oxygen species effective to kill tissue or pathogens without concern for pathogen resistance. According to the process, the active oxygen species can be divided into type I and type II active oxygen species, wherein the type II active oxygen species is singlet oxygen (1O2) Mainly, the activity is higher.
Traditional photosensitizers, such as porphyrin and cyanine compounds, have the problem of aggregation induced quenching (ACQ), namely the photosensitizers cause excitation energy dissipation due to pi-pi accumulation in an aggregation state, and the fluorescence and photodynamic therapy efficiency of the photosensitizers are greatly weakened. Aggregation Induced Emission (AIE) photosensitizers can effectively solve the problem, and the photosensitizers can avoid pi-pi accumulation through an intermolecular resistance effect in an aggregation state, so that efficient fluorescence and photodynamic therapy properties in the aggregation state are realized. However, the aggregation-induced emission photosensitizer also consumes excitation energy due to its intramolecular movement, and thus it is necessary to finely control the aggregation-induced emission photosensitizer.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provides a water-soluble aggregation-induced emission photosensitizer and a preparation method thereof. Comprises providing photosensitizer LOCK-0, LOCK-1 and LOCK-2 and its intermediate, and its structure and synthetic route are shown in figure 1.
The invention provides aggregation-induced emission photosensitizer, which is characterized by the photophysical and photochemical properties of LOCK-0, LOCK-1 and LOCK-2 in a solution. The aggregation-induced emission photosensitizer has good water solubility, almost does not emit light in an aqueous solution, can emit light strongly in a tetrahydrofuran/water (THF fraction 99%) solution, and shows typical aggregation-induced emission properties, wherein the fluorescence quantum yield of LOCK-2 in the tetrahydrofuran/water (THF fraction 99%) solution is 56.8%, which is obviously higher than that of LOCK-0 (1.2%) and LOCK-1 (1.9%), and is also higher than that of most reported aggregation-induced emission photosensitizers.
The invention also provides a preparation method of the water-soluble aggregation-induced emission photosensitizer;
(1) synthesizing an intermediate 2; dissolving the compound 1 and 4-methylquinoline in acetonitrile, stirring and heating the mixed solution to reflux for reaction; after the reaction is finished, cooling the reaction liquid to room temperature, removing the solvent by reduced pressure rotary evaporation, dissolving the residue with methanol, and then adding the residue into ether; separating out a white solid, and filtering the mixed solution to obtain a white solid, namely an intermediate 2;
(2) synthesis of intermediates 4 and 6; adding 5-bromobenzothiophene, sodium tert-butoxide and tris (dibenzylidene) acetone dipalladium into toluene, adding diphenylamine or carbazole, stirring and heating the mixed solution under the protection of nitrogen until reflux and reaction; after the reaction is finished, cooling the reaction liquid to room temperature, removing the solvent by reduced pressure rotary evaporation, and dissolving the residue with ethyl acetate and washing with water; drying, removing solvent, purifying the residue with silica gel column chromatography to obtain white solid, i.e. intermediate 4 or 6.
(3) Synthesis of intermediates 5 and 7; cooling N, N-dimethylformamide to 0 ℃, and adding phosphorus oxychloride for reaction; after the reaction is finished, dripping the dichloroethane solution of the intermediate 4 or 6 into the reaction solution for reaction; after the reaction is finished, cooling the reaction liquid to room temperature, removing the solvent by reduced pressure rotary evaporation, adding water into the remainder, and stirring to obtain a light yellow solid which is separated out; filtering to obtain a light yellow solid which is an intermediate 5 or 7;
(4) synthesizing photosensitizer LOCK-0, LOCK-1 and LOCK-2; dissolving intermediate 3, 5 or 7 and intermediate 2 in acetonitrile and adding piperidine; stirring and heating the mixed solution until reflux and reaction; after the reaction is finished, cooling the reaction liquid to room temperature, removing the solvent by reduced pressure rotary evaporation, and purifying residues by using a neutral alumina column chromatography to obtain purple, red-purple and red solids, namely the photosensitizers LOCK-0, LOCK-1 and LOCK-2.
The invention also provides application of aggregation-induced emission photosensitizers (LOCK-0, LOCK-1 and LOCK-2), which can generate singlet oxygen by being excited by light in a solution. By taking RB as a standard and ABDA as a standard1O2The singlet oxygen yield of the indicator is 91%, 130% and 206% respectively, and the high-efficiency photodynamic therapy efficiency is proved on the solution layer surface.
The technical effects are as follows:
a class of aggregation-induced emission photosensitizers (LOCK-0, LOCK-1 and LOCK-2) has dark toxicity and photodynamic therapy effect on tumor cells, and is tested by MTS/PMS cell activity experiments of HepG2 tumor cells. Experiments show that the induced luminescence photosensitizer has low dark toxicity to HepG2 cells and good biocompatibility; the compound shows obvious phototoxicity on HepG2 cells under illumination, has outstanding photodynamic treatment effect, and has higher photodynamic treatment efficiency of LOCK-0 and LOCK-2.
Drawings
FIG. 1 shows the general formula of the synthesis of LOCK series compounds, and the chemical structures and preparation processes of aggregation-induced emission photosensitizers LOCK-0, LOCK-1 and LOCK-2 and intermediates thereof.
FIG. 2 shows ultraviolet absorption spectra of aggregation-induced emission photosensitizers LOCK-0, LOCK-1 and LOCK-2 in aqueous solution and fluorescence behavior in tetrahydrofuran/aqueous solution at various ratios.
FIG. 3 shows a photodynamic active oxygen production test using H2DCF as an active oxygen indicator and aggregation-induced emission photosensitizers LOCK-0, LOCK-1 and LOCK-2.
FIG. 4 shows RB as standard and ABDA as standard1O2Indicator, aggregation-induced emission photosensitizer LOCK-0, LOCK-1 and LOCK-21O2A test is generated.
FIG. 5 shows dark toxicity and phototoxicity tests of aggregation-induced emission photosensitizers LOCK-0, LOCK-1 and LOCK-2 on tumor cells using HepG2 tumor cells as a model and MTS/PSM as an indicator.
Detailed Description
The invention will be further explained and illustrated with reference to the drawings and the specific embodiments, which are not to be considered as limiting the invention, but other embodiments obtained without inventive labour results are within the scope of protection of the invention.
As shown in figure 1, the general formula of the synthesis of LOCK series compounds, and the chemical structures and preparation processes of aggregation-induced emission photosensitizers LOCK-0, LOCK-1 and LOCK-2 and intermediates thereof. In the figure:
and (3) synthesizing an intermediate 2. Compound 1(1.91g, 4.0mmol) and 4-methylquinoline (572mg, 4.0mmol) were dissolved in 30mL acetonitrile and the mixture was heated to reflux with stirring and reacted overnight. After the reaction was completed, the reaction solution was cooled to room temperature, the solvent was removed by rotary evaporation under reduced pressure, and the residue was dissolved in 2mL of methanol and added dropwise to 100mL of vigorously stirred diethyl ether. After the addition, the mixture was allowed to stand for 30min to precipitate a white solid, and the mixture was filtered to obtain a white solid, i.e., intermediate 2, with a yield of 94%.
Synthesis of intermediates 4 and 6. 5-bromobenzothiophene (1.0g, 4.7mmol), sodium tert-butoxide (496mg, 5.2mmol), tris-dibenzylideneacetone dipalladium (215mg,. 024mmol) were added to 50mL of toluene and diphenylamine or carbazole (784mg, 4.7mmol) was added and the mixture was heated to reflux with stirring under nitrogen and reacted overnight. After completion of the reaction, the reaction solution was cooled to room temperature, the solvent was removed by rotary evaporation under reduced pressure, and the residue was dissolved in 50mL of ethyl acetate and washed 3 times with 50mL of water. The ethyl acetate solution was dried over sodium sulfate, and the solvent was removed by rotary evaporation under reduced pressure, and the residue was purified by silica gel column chromatography to obtain a white solid, i.e., intermediate 4 or 6, in yields of 81% and 86%, respectively.
Synthesis of intermediates 5 and 7. 0.4mL of N, N-dimethylformamide was cooled to 0 ℃ and 0.5mL of phosphorus oxychloride was added dropwise with stirring and reacted for 30 min. After the reaction was completed, a solution of intermediate 4 or 6(500mg, 1.7mmol) in dichloroethane (20mL) was added dropwise to the reaction mixture and reacted for 30 min. The reaction solution was stirred and gradually heated to 80 ℃ for 4 h. After completion of the reaction, the reaction solution was cooled to room temperature, the solvent was removed by rotary evaporation under reduced pressure, and 100mL of water was added to the residue and stirred to precipitate a pale yellow solid. The light yellow solid obtained after filtration was intermediate 5 or 7, with yields of 92% and 93%, respectively.
Synthesis of photosensitizers LOCK-0, LOCK-1 and LOCK-2. Intermediate 3, 5 or 7(66mg) and intermediate 2(125mg, 0.2mmol) were dissolved in 10mL of acetonitrile and 1 drop piperidine was added. The mixture was heated to reflux with stirring and reacted overnight. After the reaction is finished, cooling the reaction liquid to room temperature, removing the solvent by reduced pressure rotary evaporation, and purifying the residues by using a neutral alumina column chromatography to obtain purple, magenta and red solids, namely photosensitizer LOCK-0, LOCK-1 and LOCK-2, wherein the yield is 56%, 61% and 65% respectively.
Testing the photophysical properties of the photosensitizers LOCK-0, LOCK-1 and LOCK-2. The ultraviolet-visible absorption spectra of the aqueous solutions of the photosensitizers LOCK-0, LOCK-1 and LOCK-2 are shown in FIG. 2(A), and the maximum absorption wavelengths thereof are 523, 523 and 473nm, respectively. The fluorescence spectra of three photosensitizers in different ratios of tetrahydrofuran/water solution were tested using their maximum absorption wavelengths as excitation wavelengths. As shown in fig. 2(B) and (C), the three photosensitizers showed almost no fluorescence in aqueous solution, but were able to emit light strongly in 99% tetrahydrofuran solution, demonstrating their aggregation-induced emission properties.
Photodynamic active oxygen generation tests of the photosensitizers LOCK-0, LOCK-1 and LOCK-2. Photosensitizer (10. mu. mmol/L) was added to 5. mu. mmol/L H2DCF solution at 10mW/cm2The fluorescence spectrum (510-560nm) of the H2DCF solution was recorded by using the 488nm band as the excitation light. As shown in FIG. 3, the fluorescence intensity (PL intensity, 523nm) of H2DCF of each experimental group was gradually increased with the increase of the light irradiation time, and the photodynamic active oxygen generating ability was confirmed.
Photodynamic of photosensitizers LOCK-0, LOCK-1 and LOCK-21O2A test is generated. After recording the UV-visible absorption spectrum of a 5. mu. mmol/L photosensitizer or RB solution, ABDA (50. mu. mmol/L) was added to the solution at 10mW/cm2The solution was irradiated with white light, and the UV-visible absorption spectrum (350-410nm) of ABDA in the solution was recorded. As shown in FIG. 4, the ABDA UV-VISIBLE absorption intensity of each experimental group gradually decreased with the increase of the light irradiation time, demonstrating its photodynamic properties1O2Generating the capabilities. Integrating to obtain peak area of each group of ABDA ultraviolet-visible absorption peak, performing linear fitting on the peak area along with time change, and calculating the content of each photosensitizer by the following formula1O2Yield:
wherein phi is1O2Yield, A is a plot of the area of the UV-visible absorption peak of the photosensitizer or RB, K is the slope of the fitted curve, of RB1O2The yield was 75%. Calculated to obtain LOCK-0, LOCK-1 and LOCK-21O2The yields were 91%, 130% and 206%, respectively, demonstrating excellent photodynamic power1O2Generating the capabilities.
Photodynamic therapy test of photosensitizer LOCK-0, LOCK-1 and LOCK-2 on tumor cells. Photosensitizer (0-40 mu mmol/L) is added into tumor cell HepG2 under illumination (23 mW/cm)2) Or culturing in dark for 2 hr, culturing for 24 hr, adding MTS/PMS (20:1) to the tumor cells, and calculating the activity of the tumor cells by using the UV-visible absorption intensity of MTS at 490 nm. As shown in FIG. 5, the activity of tumor cells cultured in dark environment was almost unchanged, demonstrating the biocompatibility of the photosensitizer. The activity of the tumor cells cultured in the illumination environment is obviously reduced along with the increase of the concentration of the photosensitizer, and the photodynamic therapy capability of the photosensitizer on the tumor cells is proved.
The organic salts with aggregation-induced emission properties have excellent water solubility, and can realize high-efficiency photodynamic therapy on tumor cells. Compared with other photosensitizers, the series of organic salts can effectively avoid aggregation-induced quenching problems, and have the advantages of high fluorescence quantum yield, high singlet oxygen yield and the like.
Claims (3)
1. A kind of aggregation-induced emission photosensitizer is characterized by that it uses LOCK-0, LOCK-1 and LOCK-2 to characterize its photophysical and photochemical properties in solution.
2. A method for preparing a water-soluble aggregation-inducing emission-photosensitive agent according to claim 1;
(1) synthesizing an intermediate 2; dissolving the compound 1 and 4-methylquinoline in acetonitrile, stirring and heating the mixed solution to reflux for reaction; after the reaction is finished, cooling the reaction liquid to room temperature, removing the solvent by reduced pressure rotary evaporation, dissolving the residue with methanol, and then adding the residue into ether; separating out a white solid, and filtering the mixed solution to obtain the white solid which is the intermediate 2;
(2) synthesis of intermediates 4 and 6; adding 5-bromobenzothiophene, sodium tert-butoxide and tris (dibenzylidene) acetone dipalladium into toluene, adding diphenylamine or carbazole, stirring and heating the mixed solution under the protection of nitrogen until reflux and reaction; after the reaction is finished, cooling the reaction liquid to room temperature, removing the solvent by reduced pressure rotary evaporation, and dissolving the residue with ethyl acetate and washing with water; drying, removing the solvent, and purifying the remainder by silica gel column chromatography to obtain a white solid, namely an intermediate 4 or 6;
(3) synthesis of intermediates 5 and 7; cooling N, N-dimethylformamide to 0 ℃, and adding phosphorus oxychloride for reaction; after the reaction is finished, dripping the dichloroethane solution of the intermediate 4 or 6 into the reaction solution for reaction; after the reaction is finished, cooling the reaction liquid to room temperature, removing the solvent by reduced pressure rotary evaporation, adding water into the residue, and stirring to obtain a light yellow solid which is separated out; filtering to obtain a light yellow solid which is an intermediate 5 or 7;
(4) synthesizing photosensitizer LOCK-0, LOCK-1 and LOCK-2; dissolving intermediate 3, 5 or 7 and intermediate 2 in acetonitrile and adding piperidine; stirring and heating the mixed solution until reflux and reaction; after the reaction is finished, cooling the reaction liquid to room temperature, removing the solvent by reduced pressure rotary evaporation, and purifying residues by using a neutral alumina column chromatography to obtain purple, red-purple and red solids, namely the photosensitizers LOCK-0, LOCK-1 and LOCK-2.
3. The use of an aggregation-inducing emission photosensitizer according to claim 1, which is excited in solution by light to generate singlet oxygen.
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