An organic photosensitizer of pyridinium salt and its preparation method and application

Abstract

This patent application discloses a pyridinium salt-based organic photosensitizer and its preparation method. The pyridinium salt-based organic photosensitizer is a pyridinium salt compound based on tetraphenylethylene or N-phenylcarbazole, specifically including 12 kinds in total, namely TPE-Py, TPE-Pys-M, TPE-Pys-B, TPE-Pys-BP, BK-Py, BK-Pys-M, BK-Pys-B, BK-Pys-BP, BKD-Pys-BP, BKB-Pys-BP, and BKT-Pys-BP. By combining the strong electron-withdrawing ability of pyridinium salt with the electron-donating characteristics of tetraphenylethylene and carbazole, the HOMO-LUMO orbitals of the molecule are more separated, which is beneficial to reducing ΔEst. At the same time, by utilizing the strong intersystem crossing ability of benzophenone, the orbital spin coupling (SOC) can be enhanced, thereby enhancing the ability to generate reactive oxygen species and further improving the photodynamic therapy effect.

Description

Technical Field

[0001] This patent application relates to the field of organic light-emitting materials, and more specifically, to a pyridinium salt-based organic photosensitizer, its preparation method and application. Background Art

[0002] Malignant tumors have had a serious impact on human physical health and social and economic development. At present, the diagnosis and treatment of tumors remain the key research points and difficulties for chemists, biologists and medical workers. In recent years, fluorescence imaging diagnosis and optical therapy have become research hotspots for tumor diagnosis and treatment due to their advantages of high-sensitivity imaging and highly targeted therapy. Photodynamic therapy has gradually come into people's view due to its advantages such as non-invasiveness and non-drug resistance.

[0003] Of course, while photodynamic therapy is developing, it also faces challenges, such as how to solve tumor targeting, how to combine with traditional treatment modes, and how to develop more efficient photosensitizers. Therefore, finding a highly efficient photosensitizer that can improve the yield of reactive oxygen species to achieve tumor diagnosis and treatment integration is an urgent problem to be solved by researchers in this field. Summary of the Invention

[0004] To overcome one of the above-mentioned existing technical problems, the present invention provides a pyridinium salt-based organic photosensitizer, which has the advantage of high reactive oxygen generation efficiency.

[0005] Another object of the present invention is to provide a preparation method of a pyridinium salt-based organic photosensitizer.

[0006] Another object of the present invention is to provide an application of a pyridinium salt-based organic photosensitizer.

[0007] To solve the above technical problems, the technical solution adopted by the present invention is:

[0008] A pyridinium salt-based organic photosensitizer, the pyridinium salt-based organic photosensitizer is a pyridinium salt based on tetraphenylethylene, and has one of the following molecular structures:

[0009]

[0010] This patent application also provides a preparation method of the above pyridinium salt-based organic photosensitizer, including the following steps:

[0011] S11. Preparation of intermediate 4-bromomethyl benzophenone (BP-M-Br)

[0012] 4-Methyl benzophenone and N-bromosuccinimide (NBS) are irradiated with a high-pressure mercury lamp, and the NBS bromination reaction is initiated by benzoyl peroxide (BPO) to obtain 4-bromomethyl benzophenone (BP-M-Br) with bromine substitution at the benzyl position;

[0013] S12. Preparation of the final product 4-(4-(1,2,2-triphenylethynyl)phenyl)pyridine (TPE-Py)

[0014] Using the Suzuki coupling reaction, 1-(4-bromophenyl)-1,2,2-triphenylethylene, 4-pyridineboronic acid, potassium carbonate, and tetrakis(triphenylphosphine)palladium were dissolved in a mixed system of tetrahydrofuran and methanol, and reacted under N 2 protection and at 80 °C to prepare 4-(4-(1,2,2-triphenylethynyl)phenyl)pyridine (TPE-Py);

[0015] S13. Preparation of the final products TPE-Pys-M, TPE-Pys-B, and TPE-Pys-BP

[0016] Using the Menshutkin reaction, the product TPE-Py obtained in step S12 was refluxed with methyl iodide, benzyl bromide, and the product BP-M-Br from step S11 in tetrahydrofuran to obtain 1-methyl-4-(4-(1,2,2-triphenylethynyl)phenyl)pyridinium iodide (TPE-Pys-M), 1-benzyl-4-(4-(1,2,2-triphenylethynyl)phenyl)pyridinium bromide (TPE-Pys-B), and 1-(4-benzoylbenzyl)-4-(4-(1,2,2-triphenylethynyl)phenyl)pyridinium bromide (TPE-Pys-BP).

[0017] Preferably, the NBS bromination in step S11 requires inert gas protection, and the reaction time is 3 to 6 hours.

[0018] Preferably, the solvent used in step S12 is THF:CH 3 OH = 1:1, the catalyst used is Pd(PPh 3 ) 4 (6-8%), and inert gas protection is required.

[0019] Preferably, the molar ratio of TPE-Py to CH 3 I is 1:(2-3), and the reaction molar ratio of benzyl bromide to BP-M-Br is 1:(1-1.05), the reaction temperature is 80 °C, and the time is 12 hours.

[0020] This patent application also provides another pyridinium salt-based organic photosensitizer, and the pyridinium salt-based organic photosensitizer is a pyridinium salt based on N-phenylcarbazole and has one of the following molecular structures:[[]]

[0021]

[0022] This patent application also provides a preparation method for the above pyridinium salt organic photosensitizers, which includes the following steps:

[0023] S21. Preparation of the final product 9-(4-(4-pyridyl)phenyl)-9H-carbazole (BK-Py)

[0024] Using the Suzuki coupling reaction, dissolve 9-(4-bromophenyl)carbazole, 4-pyridineboronic acid, potassium carbonate, and tetrakis(triphenylphosphine)palladium in a mixed system of tetrahydrofuran and methanol, and react at 80 °C under N 2 protection to prepare 9-(4-(4-pyridyl)phenyl)-9H-carbazole (BK-Py);

[0025] S22. Preparation of the final products 4-(4-(9H-carbazol-9-yl)phenyl)-1-methylpyridin-1-ium iodide (BK-Pys-M), 4-(4-(9H-carbazol-9-yl)phenyl)-1-benzylpyridin-1-ium bromide (BK-Pys-B), and 4-(4-(9H-carbazol-9-yl)phenyl)-1-(4-benzoylbenzyl)pyridin-1-ium bromide (BK-Pys-BP)

[0026] Using the Menshutkin reaction, reflux the product BK-Py obtained in step S21 with iodomethane, benzyl bromide, and the product BP-M-Br in step S11 in tetrahydrofuran to obtain 4-(4-(9H-carbazol-9-yl)phenyl)-1-methylpyridin-1-ium iodide (BK-Pys-M), 4-(4-(9H-carbazol-9-yl)phenyl)-1-benzylpyridin-1-ium bromide (BK-Pys-B), and 4-(4-(9H-carbazol-9-yl)phenyl)-1-(4-benzoylbenzyl)pyridin-1-ium bromide (BK-Pys-BP);

[0027] S23. Preparation of the intermediate 1-(4-benzoylbenzyl)-4-methylpyridin-1-ium bromide (BP-M-Pys)

[0028] Using the Menshutkin reaction, reflux 4-bromomethyl benzophenone, the product in S11, with 4-methylpyridine in tetrahydrofuran to obtain 1-(4-benzoylbenzyl)-4-methylpyridin-1-ium bromide (BP-M-Pys);

[0029] S24. Preparation of the intermediate 9-(4-bromophenyl)carbazole-4-carbaldehyde (BKB-CHO)

[0030] Using the Suzuki coupling reaction, dissolve 9-(4-bromophenyl)carbazole, 4-formylphenylboronic acid, potassium carbonate, and tetrakis(triphenylphosphine)palladium in a mixed system of tetrahydrofuran and methanol, and at N2 Protect and react at 80 °C to prepare 9-(4-bromophenyl)carbazole-4-benzaldehyde (BKB-CHO);

[0031] S25. Preparation of intermediate 9-(4-bromophenyl)carbazole-4-thiophenecarboxaldehyde (BKT-CHO)

[0032] Using the Suzuki coupling reaction, dissolve 9-(4-bromophenyl)carbazole, 5-formyl-2-thiopheneboronic acid, potassium carbonate and tetrakis(triphenylphosphine)palladium in a mixed system of tetrahydrofuran and methanol, and react under N 2 Protect and react at 80 °C to prepare 9-(4-bromophenyl)carbazole-4-thiophenecarboxaldehyde (BKT-CHO);

[0033] S26. Preparation of final products BKD-Pys-BP, BKB-Pys-BP and BKT-Pys-BP

[0034] React the product BP-M-Pys obtained in step S23 with N-(4-formylphenyl)carbazole, BKB-CHO and BKT-CHO under the catalysis of a small amount of piperidine for dehydration condensation to obtain (E)-4-(4-(9H-carbazol-9-yl)styryl)-1-(4-benzoylbenzyl)pyridinium bromide (BKD-Pys-BP), (E)-4-(2-(4'-(9H-carbazol-9-yl)-[1,1'-biphenyl]-4-yl)vinyl)-1-(4-benzoylbenzyl)pyridinium bromide (BKB-Pys-BP) and (E)-4-(2-(5-(4-(9H-carbazol-9-yl)phenyl)thiophen-2-yl)vinyl)-1-(4-benzoylbenzyl)pyridinium bromide (BKT-Pys-BP).

[0035] Preferably, in step 22, the molar ratio of the intermediate BK-Py to CH 3 I is 1:(2 - 3), the reaction molar ratio of BK-Py to BP-M-Br is 1:(1 - 1.05), the reaction temperature is 80 °C, and the time is 12 hours.

[0036] Preferably, in step S23, the reaction molar ratio of BP-M-Br to 4-methylpyridine is 1:1.

[0037] This patent application also provides an organic photosensitizer for photodynamic therapy, and the organic photosensitizer uses the pyridinium salt organic photosensitizer as described above.

[0038] Compared with the prior art, the beneficial effects of this patent application are:

[0039] The synthesis method of pyridinium salt-based organic photosensitizers based on tetraphenylethylene and N-phenylcarbazole provided by this patent application uses propeller-shaped tetraphenylethylene and N-phenylcarbazole as the basic skeletons, and prepares a series of aggregation-induced emission materials by modifying pyridinium salts. Combining the strong electron-withdrawing ability of pyridinium salts with the electron-donating characteristics of tetraphenylethylene or carbazole makes the HOMO-LUMO orbitals of the molecule more separated, which is beneficial to reducing ΔEst (the energy gap between the lowest excited singlet (S1) and the lowest excited triplet (T1), the energy gap between the lowest excited singlet(S1)and the lowest excited triplet(T1).); At the same time, the strong intersystem crossing ability of benzophenone can enhance the orbital spin coupling (SOC), thereby enhancing the ability to generate reactive oxygen species and further improving the photodynamic therapy effect. The development and application of aggregation-induced emission (AIE)-type highly efficient photosensitizers will open up a new path for tumor localization and treatment. Description of the Drawings

[0040] Figure 1 1H NMR spectrum of the compound BP-M-Br prepared in step S11. 1 1H NMR spectrum.

[0041] Figure 2 1H NMR spectrum of the compound TPE-Py prepared in step S12. 1 1H NMR spectrum.

[0042] Figure 3 1H NMR spectrum of the compound TPE-Pys-M prepared in step S13. 1 1H NMR spectrum.

[0043] Figure 4 1H NMR spectrum of the compound TPE-Pys-M prepared in step S13. 13 13C NMR spectrum.

[0044] Figure 5 1H NMR spectrum of the compound TPE-Pys-B prepared in step S13. 1 1H NMR spectrum.

[0045] Figure 6 1H NMR spectrum of the compound TPE-Pys-B prepared in step S13. 13 13C NMR spectrum.

[0046] Figure 7 1H NMR spectrum of the compound TPE-Pys-BP prepared in step S13. 1 1H NMR spectrum.

[0047] Figure 8 1H NMR spectrum of the compound TPE-Pys-BP prepared in step S13.13 13C NMR spectrum

[0048] Figure 9 1H NMR spectrum of the compound BK-Py prepared in step S21 1 1H NMR spectrum

[0049] Figure 10 1H NMR spectrum of the compound BK-Pys-M prepared in step S22 1 1H NMR spectrum

[0050] Figure 11 1H NMR spectrum of the compound BK-Pys-M prepared in step S22 13 13C NMR spectrum

[0051] Figure 12 1H NMR spectrum of the compound BK-Pys-B prepared in step S22 1 1H NMR spectrum

[0052] Figure 13 1H NMR spectrum of the compound BK-Pys-B prepared in step S22 13 13C NMR spectrum

[0053] Figure 14 1H NMR spectrum of the compound BK-Pys-BP prepared in step S22 1 1H NMR spectrum

[0054] Figure 15 1H NMR spectrum of the compound BK-Pys-BP prepared in step S22 13 13C NMR spectrum

[0055] Figure 16 1H NMR spectrum of the compound BP-M-Pys prepared in step S23 1 1H NMR spectrum

[0056] Figure 17 1H NMR spectrum of the compound BKB-CHO prepared in step S24 1 1H NMR spectrum

[0057] Figure 18 1H NMR spectrum of the compound BKT-CHO prepared in step S25 1 1H NMR spectrum

[0058] Figure 19 1H NMR spectrum of the compound BKD-Pys-BP prepared in step S26 1 1H NMR spectrum

[0059] Figure 20 1H NMR spectrum of the compound BKD-Pys-BP prepared in step S26 13 13C NMR spectrum

[0060] Figure 21 The 1 H NMR spectrum of the compound BKB-Pys-BP prepared in step S26.

[0061] Figure 22 The 13 C NMR spectrum of the compound BKB-Pys-BP prepared in step S26.

[0062] Figure 23 The 1 H NMR spectrum of the compound BKT-Pys-BP prepared in step S26.

[0063] Figure 24 The 13 C NMR spectrum of the compound BKT-Pys-BP prepared in step S26.

[0064] Figure 25 The UV absorption spectra in dimethyl sulfoxide and the photoluminescence spectra in the solid state of the products (TPE-Py, TPE-Pys-M, TPE-Pys-B, TPE-Pys-BP) obtained in steps S12 and S13.

[0065] Figure 26 The AIE characteristic spectra of the products (TPE-Py, TPE-Pys-M, TPE-Pys-B, TPE-Pys-BP) obtained in steps S12 and S13 in a mixed solvent of dichloromethane and n-hexane.

[0066] Figure 27 The line graph of the reactive oxygen species generation ability of the products (TPE-Py, TPE-Pys-M, TPE-Pys-B, TPE-Pys-BP) obtained in steps S12 and S13.

[0067] Figure 28 The UV absorption spectra in dimethyl sulfoxide and the photoluminescence spectra in the solid state of the products (BK-Py, BK-Pys-M, BK-Pys-B, BK-Pys-BP, BKD-Pys-BP, BKB-Pys-BP, BKT-Pys-BP) obtained in steps S21, 22 and S26.

[0068] Figure 29 The AIE characteristic spectra of the products (BK-Py, BK-Pys-M, BK-Pys-B, BK-Pys-BP, BKD-Pys-BP, BKB-Pys-BP, BKT-Pys-BP) obtained in steps S21, 22 and S26 in a mixed solvent of dichloromethane and n-hexane.

[0069] Figure 30Line graph of the reactive oxygen species generation ability of the products (BK-Py, BK-Pys-M, BK-Pys-B, BK-Pys-BP, BKD-Pys-BP, BKB-Pys-BP, BKT-Pys-BP) obtained in steps S21, 22 and S26. Detailed implementation mode

[0070] The following will describe in detail the implementation schemes of this patent application in combination with the embodiments. However, those skilled in the art will understand that the following embodiments are only used to illustrate this patent application and should not be regarded as limiting the scope of this patent application. For those not specified in the embodiments, they are carried out according to the conventional conditions or the conditions recommended by the manufacturer. For the reagents or instruments not specified for the manufacturer, they are all conventional products that can be obtained through commercial purchase.

[0071] It should be noted that:

[0072] In this patent application, if there is no special indication, all the implementation modes and preferred implementation methods mentioned in this article can be combined with each other to form a new technical solution.

[0073] In this patent application, if there is no special indication, the percentage (%) or part refers to the weight percentage or weight part relative to the composition.

[0074] In this patent application, if there is no special indication, the various components involved or their preferred components can be combined with each other to form a new technical solution.

[0075] In this patent application, unless otherwise stated, the numerical range "a~b" represents the abbreviated representation of any real number combination between a and b, where a and b are both real numbers. For example, the numerical range "6~15" means that all the real numbers between "4~6" have been fully listed in this article, and "4~6" is just the abbreviated representation of these numerical combinations.

[0076] The "range" disclosed in this patent application can be in the form of one or more lower limits and one or more upper limits respectively.

[0077] In this patent application, unless otherwise stated, each reaction or operation step can be carried out in sequence or in reverse order. Preferably, the reaction methods in this article are carried out in sequence.

[0078] Unless otherwise stated, the professional and scientific terms used in this article have the same meaning as those familiar to those skilled in the art. In addition, any method or material similar or equivalent to the recorded content can also be applied to this patent application.

[0079] This patent application provides a pyridinium salt-based organic photosensitizer, which is a pyridinium salt based on tetraphenylethylene and has one of the following molecular structures:

[0080]

[0081] From left to right, the second to the fourth pyridinium salt-based organic photosensitizers are respectively named: 1-methyl-4-(4-(1,2,2-triphenylvinyl)phenyl)pyridin-1-ium iodide (abbreviation: TPE-Pys-M), 1-benzyl-4-(4-(1,2,2-triphenylvinyl)phenyl)pyridin-1-ium bromide (abbreviation: TPE-Pys-B), and 1-(4-benzoylbenzyl)-4-(4-(1,2,2-triphenylvinyl)phenyl)pyridin-1-ium bromide (abbreviation: TPE-Pys-BP).

[0082] This patent application also provides a pyridinium salt organic photosensitizer based on N-phenylcarbazole and has one of the following molecular structures:

[0083]

[0084] From left to right, the second to the seventh pyridinium salt-based organic photosensitizers are respectively named: 4-(4-(9H-carbazol-9-yl)phenyl)-1-methylpyridin-1-ium iodide (abbreviation: BK-Pys-M), 4-(4-(9H-carbazol-9-yl)phenyl)-1-benzylpyridin-1-ium bromide (abbreviation: BK-Pys-B), 4-(4-(9H-carbazol-9-yl)phenyl)-1-(4-benzoylbenzyl)pyridin-1-ium bromide (abbreviation: BK-Pys-BP), (E)-4-(4-(9H-carbazol-9-yl)styryl)-1-(4-benzoylbenzyl)pyridin-1-ium bromide (abbreviation: BKD-Pys-BP), (E)-4-(2-(4'-(9H-carbazol-9-yl)-[1,1'-biphenyl]-4-yl)vinyl)-1-(4-benzoylbenzyl)pyridin-1-ium bromide (abbreviation: BKB-Pys-BP), and (E)-4-(2-(5-(4-(9H-carbazol-9-yl)phenyl)thiophen-2-yl)vinyl)-1-(4-benzoylbenzyl)pyridin-1-ium bromide (abbreviation: BKT-Pys-BP).

[0085] The pyridinium salt-based organic photosensitizer based on tetraphenylethylene and N-phenylcarbazole provided in this patent application can be used as an aggregation-induced emission material. The pyridinium salt-based organic photosensitizer in this patent application combines the strong electron-withdrawing ability of pyridinium salt with the electron-donating characteristics of tetraphenylethylene or carbazole, making the HOMO-LUMO orbitals of the molecule more separated, which is beneficial to reducing ΔEst; at the same time, the strong intersystem crossing ability of benzophenone can enhance the orbital spin coupling (SOC), thereby enhancing the ability to generate reactive oxygen species and further improving the photodynamic therapy effect. The development and application of AIE-type highly efficient photosensitizers will open up a new path for tumor localization and treatment.

[0086] This patent application also provides a method for synthesizing a pyridinium salt-based organic photosensitizer based on tetraphenylethylene. The method includes the following steps:

[0087] S11. Preparation of intermediate 4-bromomethylbenzophenone (BP-M-Br)

[0088] 4-Methylbenzophenone and N-bromosuccinimide (NBS) are irradiated under a high-pressure mercury lamp (125 W), and the bromination reaction of NBS is initiated by benzoyl peroxide (BPO) to obtain 4-bromomethylbenzophenone (BP-M-Br) with bromine substitution at the benzyl position.

[0089] S12. Preparation of the final product 4-(4-(1,2,2-triphenylethenyl)phenyl)pyridine (TPE-Py)

[0090] Using the Suzuki coupling reaction, 1-(4-bromophenyl)-1,2,2-triphenylethylene, 4-pyridineboronic acid, potassium carbonate, and tetrakis(triphenylphosphine)palladium are dissolved in a mixed system of tetrahydrofuran and methanol, and reacted at 80 °C under N 2 protection to prepare 4-(4-(1,2,2-triphenylethenyl)phenyl)pyridine (TPE-Py).

[0091] S13. Preparation of the final products TPE-Pys-M, TPE-Pys-B, and TPE-Pys-BP

[0092] Using the Menshutkin reaction, the product TPE-Py obtained in step S12 is refluxed with methyl iodide, benzyl bromide, and the product BP-M-Br in step S11 in tetrahydrofuran to obtain 1-methyl-4-(4-(1,2,2-triphenylethenyl)phenyl)pyridinium-1-iodide (TPE-Pys-M), 1-benzyl-4-(4-(1,2,2-triphenylethenyl)phenyl)pyridinium-1-bromide (TPE-Pys-B), and 1-(4-benzoylbenzyl)-4-(4-(1,2,2-triphenylethenyl)phenyl)pyridinium-1-bromide (TPE-Pys-BP) respectively.

[0093] In step S11 of some preferred embodiments of this patent application, the molar ratio of 4-methylbenzophenone to NBS is 1:(1.05 - 1.1), and the addition amount of BPO is 5 mg / 1 mol of reaction. In this NBS bromination reaction, BPO is used as an initiator, and the addition time is when the temperature rises to about 50 °C.

[0094] In some preferred embodiments of this patent application, the reaction in step S11 requires photoinitiation. A self-ballasted high-pressure mercury lamp is used as a light source to provide energy. The power of the mercury lamp used is 125 W. During use, the lamp is turned off once every 1 h and restarted for lighting after 15 minutes.

[0095] In some preferred embodiments of this patent application, the reaction in step S11 uses CCl 4 as a reaction solvent, and dissolution is ensured as much as possible before the reaction. The conditions for this methyl bromination reaction are heating under reflux under an inert gas protection. The inert atmosphere includes a nitrogen atmosphere, an argon atmosphere, and a helium atmosphere. More preferably, the inert atmosphere in this step is selected as a nitrogen (N 2 ) atmosphere.

[0096] In some preferred embodiments of this patent application, after step S11 ends, the reaction solution is cooled to room temperature and then the crude product is obtained by rotary evaporation. The crude product is dissolved in dichloromethane and then mixed with silica gel. Then, petroleum ether is used as an eluent for silica gel column chromatography to separate the required product.

[0097] In a more preferred embodiment of this patent application, the specific operation steps of step S11 are as follows:

[0098] 4-Methylbenzophenone (0.98 g, 196.24 g / mol, 5 mmol) and N-bromosuccinimide (NBS, 0.98 g, 177.98 g / mol, 5.5 mmol) are added to a 100 mL three-necked round-bottom flask. Benzoyl peroxide (BPO, 25 mg) is placed separately in a balloon. Then, CCl 4 (30 mL) is used to dissolve the raw materials. The reaction is heated to 50 °C in an N 2 environment. Then, BPO is added to the reaction system in small portions. After the addition is complete, the temperature is raised to 80 °C and the high-pressure mercury lamp (125 W) is turned on. The high-pressure mercury lamp is turned off once every 1 hour, and the total lighting time is 4 hours. Finally, the reaction solution is concentrated under reduced pressure, and the product is separated by column chromatography using petroleum ether as an eluent, and a white solid can be obtained (yield: 95%).

[0099] The reaction equation is as follows:

[0100]

[0101] AsFigure 1 As shown, the intermediate BP-M-Br can be obtained through nuclear magnetic resonance spectrum characterization. The nuclear magnetic data of this intermediate BP-M-Br are as follows: 1 H NMR(400MHz,CDCl 3 )δ(TMS,ppm):7.82 - 7.77(m,4H),7.60(dd,J=10.5,4.3Hz,1H),7.53 - 7.46(m,4H),4.54(s,2H).

[0102] In step S12 of some preferred embodiments of this patent application, the catalyst selected for the Suzuki reaction is tetrakis(triphenylphosphine)palladium, the base used is potassium carbonate or sodium carbonate, and the molar ratio of 1-(4-bromophenyl)-1,2,2-triphenylethylene, 4-pyridineboronic acid, potassium carbonate and tetrakis(triphenylphosphine)palladium is 1:1.5:2:(5% - 8%).

[0103] In some preferred embodiments of this patent application, the reaction solvent selected in step S12 is tetrahydrofuran (THF) and methanol (CH 3 OH) (volume ratio = 1:1). During use, tetrahydrofuran is preferably added first, and then methanol is added to ensure dissolution. The reaction conditions are heating under reflux under the protection of an inert gas. The inert atmosphere includes a nitrogen atmosphere, an argon atmosphere and a helium atmosphere, and the inert atmosphere in this step is a nitrogen atmosphere. Finally, the reaction temperature is set at 80 °C and the reaction time is 24 hours.

[0104] In some preferred embodiments of this patent application, after step S12, the reaction solution is cooled to room temperature. After removing the reaction solution by reduced pressure concentration, the crude product is dissolved in dichloromethane and mixed with silica gel. Then, column chromatography is used, and a mixed solution of petroleum ether and ethyl acetate is used as the eluent for column chromatography separation and purification. The volume ratio is (ethyl acetate:petroleum ether = 50:1). Finally, one of the final products, TPE-Py, is obtained.

[0105] In a more preferred embodiment of this patent application, the specific operation steps of step S12 are as follows:

[0106] 1-(4-bromophenyl)-1,2,2-triphenylethylene (2.87g, 410.07g / mol, 7mmol), 4-pyridineboronic acid (1.3g, 122.92g / mol, 10.5mmol), tetrakis(triphenylphosphine)palladium (Pd(PPh 3 ) 4 , 0.48g, 1155.57g / mol, 0.42mmol) and potassium carbonate (K 2 CO 3, 1.93 g, 138.21 g / mol, 14 mmol) was added to a 100 mL two-necked round-bottom flask in this order, and then tetrahydrofuran and methanol were added to the round-bottom flask at a volume ratio of 1:1. The reaction was heated to 80 °C in an N 2 atmosphere and reacted for 24 h. After the reaction, the crude product was obtained by concentration under reduced pressure and purified by column chromatography. The eluent was ethyl acetate: petroleum ether = 50:1 (volume ratio), and finally a white solid was obtained (yield: 80%).

[0107] The reaction equation is as follows:

[0108]

[0109] As Figure 2 shown, the compound TPE-Py can be obtained through nuclear magnetic resonance spectrum characterization. The nuclear magnetic data of the compound TPE-Py are as follows: 1 H NMR (400 MHz, CDCl 3 ) δ 8.60 (d, J = 6.2 Hz, 2H), 7.44 (d, J = 6.2 Hz, 2H), 7.39 (d, J = 8.4 Hz, 2H), 7.17 - 7.09 (m, 11H), 7.08 - 7.00 (m, 6H).

[0110] In some preferred embodiments of this patent application, in step S13, the solvents selected for the Menshutkin reaction are dichloromethane, ethanol, and tetrahydrofuran. More preferably, the polar aprotic solvent tetrahydrofuran is used as the reaction solvent to completely dissolve the raw materials, but the solvent should not be in excess, and just enough to dissolve is appropriate. The reaction temperature is 80 °C, and the reaction time is 24 h.

[0111] In some preferred embodiments of this patent application, in step S13, since methyl iodide is volatile, it is more preferably to react with a molar ratio of TPE-Py to methyl iodide of 1:(2 - 3), rather than 1:(1 - 1.05); the other two products are both reacted with a molar ratio of 1:(1 - 1.05). Solids will precipitate during the reaction, and the product adsorbed on the edge of the round-bottom flask can be scraped back into the solvent with a spatula to ensure full reaction.

[0112] In some preferred embodiments of this patent application, after step S13, the reaction solution is fully cooled to precipitate the product in solid form, followed by suction filtration to collect the filter residue, and then the crude product is washed with a small amount of n-hexane multiple times. More preferably, a centrifuge is used for washing and impurity removal. Finally, the product is dried under vacuum to obtain a product that basically meets the requirements for analysis and testing. More preferably, column chromatography separation can also be carried out using neutral alumina, and the eluents are used in the order of dichloromethane, ethyl acetate, and methanol.

[0113] In a more preferred embodiment of this patent application, the specific operation steps of step S13 are as follows:

[0114] Step 131 Preparation of TPE-Pys-M

[0115] Dissolve TPE-Py (0.21 g, 409.53 g / mol, 0.5 mmol) in 20 mL of tetrahydrofuran. Subsequently, accurately measure methyl iodide (0.21 g, 141.9 g / mol, 1.5 mmol) and add it to the reaction solution. Heat the reaction solution to 80 °C and react for 24 h. After the reaction is completed, filter the precipitate in the reaction solution, and wash the filter residue several times with a mixed solution of tetrahydrofuran and n-hexane to obtain a crude product. The crude product is separated by column chromatography using neutral alumina, and the eluents are used in the order of dichloromethane, ethyl acetate, and methanol. The finally obtained product is a yellow solid (yield: 86%).

[0116] The reaction equation is as follows:

[0117]

[0118] As Figure 3 shown by the proton nuclear magnetic resonance spectrum and Figure 4 carbon nuclear magnetic resonance spectrum, the characterization of the compound TPE-Pys-M can be obtained. The nuclear magnetic data are as follows: 1 HNMR (400 MHz, CDCl 3 ) δ 9.24 (d, J = 6.7 Hz, 2H), 8.12 (d, J = 6.7 Hz, 2H), 7.54 (d, J = 8.4 Hz, 2H), 7.22 (d, J = 8.4 Hz, 2H), 7.17 - 7.09 (m, 9H), 7.06 - 6.99 (m, 6H), 4.63 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ) δ 155.79, 148.93, 145.41, 143.37, 142.97, 142.93, 142.79, 139.22, 132.89, 131.31, 131.28, 131.23, 130.91, 128.09, 128.03, 127.77, 127.24, 127.21, 126.99, 124.32, 48.63.

[0119] Step 132 Preparation of TPE-Pys-B

[0120] TPE-Py (0.21 g, 409.53 g / mol, 0.5 mmol) was dissolved in 20 mL of tetrahydrofuran. Subsequently, benzyl bromide (0.094 g, 171.04 g / mol, 0.55 mmol) was accurately measured and added to the reaction solution. Then, the temperature was raised to 80 °C and the reaction was carried out for 24 h. After monitoring the completion of the reaction by thin-layer chromatography, the precipitate in the reaction solution was filtered, and the filter residue was washed several times with a mixed solution of tetrahydrofuran and n-hexane to obtain the crude product. The crude product was separated by column chromatography on neutral alumina, and the eluents were used in the order of dichloromethane, ethyl acetate, and methanol. The final product obtained was a yellow-green solid (yield: 88%).

[0121] The reaction equation is as follows:

[0122]

[0123] As Figure 5 shown by the 1H NMR spectrum of Figure 6 and the 13C NMR spectrum of 1 H NMR (400 MHz, DMSO) δ 9.19 (d, J = 6.7 Hz, 2H), 8.48 (d, J = 6.8 Hz, 2H), 7.91 (d, J = 8.4 Hz, 2H), 7.55 (d, J = 6.3 Hz, 2H), 7.45 (d, J = 7.1 Hz, 3H), 7.25 - 7.11 (m, 11H), 7.08 - 6.97 (m, 6H), 5.84 (s, 2H). 13 C NMR (101 MHz, DMSO) δ 154.65, 148.04, 145.15, 143.20, 143.18, 143.03, 142.71, 139.86, 135.07, 132.36, 131.58, 131.17, 131.14, 131.06, 129.73, 129.67, 129.14, 128.55, 128.53, 128.35, 128.22, 127.54, 127.36, 124.92, 62.64.

[0124] Step 133 Preparation of TPE-Pys-BP

[0125] Dissolve TPE-Py (0.41 g, 409.53 g / mol, 1 mmol) and BP-M-Br (0.31 g, 275.15 g / mol, 1.1 mmol) in 30 mL of tetrahydrofuran. Then, heat the reaction solution to 80 °C and react for 24 h. A large amount of solid will precipitate during the reaction. After monitoring the reaction by thin-layer chromatography until it ends, filter the precipitate in the reaction solution, and wash the filter residue several times with a mixed solution of tetrahydrofuran and n-hexane to obtain the crude product. The crude product is separated by column chromatography on neutral alumina, and the eluents are used in the order of dichloromethane, ethyl acetate, and methanol. Finally, the product obtained is a yellow-green solid (yield: 85%).

[0126] The reaction equation of this reaction is as follows:

[0127]

[0128] As Figure 7 shown by the 1H NMR spectrum of Figure 8 and the 13C NMR spectrum of 1 H NMR (400 MHz, DMSO) δ 9.24 (d, J = 6.5 Hz, 2H), 8.53 (d, J = 6.6 Hz, 2H), 7.93 (d, J = 8.3 Hz, 2H), 7.79 (d, J = 8.1 Hz, 2H), 7.71 (dd, J = 12.1, 7.8 Hz, 5H), 7.57 (t, J = 7.5 Hz, 2H), 7.26 - 7.11 (m, 11H), 7.02 (dd, J = 17.3, 9.4 Hz, 6H), 5.98 (s, 2H). 13 C NMR (101 MHz, DMSO) δ 195.72, 154.82, 148.07, 145.40, 143.19, 143.02, 142.74, 139.85, 139.28, 138.06, 137.07, 133.48, 132.39, 131.54, 131.17, 131.15, 131.06, 130.73, 130.15, 129.15, 128.54, 128.35, 128.26, 127.56, 127.37, 124.99, 62.09.

[0129] This patent application also provides a method for synthesizing N-phenylcarbazole pyridinium salt-based organic photosensitizers. The method includes the following steps:

[0130] S21. Preparation of the final product 9-(4-(4-pyridyl)phenyl)-9H-carbazole (BK-Py)

[0131] Using the Suzuki coupling reaction, 9-(4-bromophenyl)carbazole, 4-pyridineboronic acid, potassium carbonate and tetrakis(triphenylphosphine)palladium are dissolved in a mixed system of tetrahydrofuran and methanol, and the reaction is carried out under N 2 protection and at 80 °C to prepare 9-(4-(4-pyridyl)phenyl)-9H-carbazole (BK-Py);

[0132] S22. Preparation of the final products ammonium 4-(4-(9H-carbazol-9-yl)phenyl)-1-methylpyridin-1-ium iodide (BK-Pys-M), ammonium 4-(4-(9H-carbazol-9-yl)phenyl)-1-benzylpyridin-1-ium bromide (BK-Pys-B) and ammonium 4-(4-(9H-carbazol-9-yl)phenyl)-1-(4-benzoylbenzyl)pyridin-1-ium bromide (BK-Pys-BP)

[0133] Using the Menshutkin reaction, the product BK-Py obtained in step S21 is refluxed with iodomethane, benzyl bromide and the product BP-M-Br in step S11 in tetrahydrofuran to obtain ammonium 4-(4-(9H-carbazol-9-yl)phenyl)-1-methylpyridin-1-ium iodide (BK-Pys-M), ammonium 4-(4-(9H-carbazol-9-yl)phenyl)-1-benzylpyridin-1-ium bromide (BK-Pys-B) and ammonium 4-(4-(9H-carbazol-9-yl)phenyl)-1-(4-benzoylbenzyl)pyridin-1-ium bromide (BK-Pys-BP);

[0134] S23. Preparation of the intermediate 1-(4-benzoylbenzyl)-4-methylpyridin-1-ium bromide (BP-M-Pys)

[0135] Using the Menshutkin reaction, 4-bromomethyl benzophenone and 4-methylpyridine are refluxed in tetrahydrofuran to obtain 1-(4-benzoylbenzyl)-4-methylpyridin-1-ium bromide (BP-M-Pys);

[0136] S24. Preparation of the intermediate 9-(4-bromophenyl)carbazole-4-carbaldehyde (BKB-CHO)

[0137] Using the Suzuki coupling reaction, 9-(4-bromophenyl)carbazole, 4-formylphenylboronic acid, potassium carbonate and tetrakis(triphenylphosphine)palladium are dissolved in a mixed system of tetrahydrofuran and methanol, and the reaction is carried out under N 2 protection and at 80 °C to prepare 9-(4-bromophenyl)carbazole-4-carbaldehyde (BKB-CHO);

[0138] S25. Preparation of the intermediate 9-(4-bromophenyl)carbazole-4-thiophenecarbaldehyde (BKT-CHO)

[0139] Using the Suzuki coupling reaction, 9-(4-bromophenyl)carbazole, 5-formyl-2-thiopheneboronic acid, potassium carbonate and tetrakis(triphenylphosphine)palladium were dissolved in a mixed system of tetrahydrofuran and methanol, and the reaction was carried out at 80 °C under N 2 protection to prepare 9-(4-bromophenyl)carbazole-4-thiophenealdehyde (BKT-CHO);

[0140] S26. Preparation of the final products BKD-Pys-BP, BKB-Pys-BP and BKT-Pys-BP

[0141] The product BP-M-Pys obtained in step S23 was subjected to dehydration condensation with N-(4-formylphenyl)carbazole, BKB-CHO and BKT-CHO under the catalysis of a small amount of piperidine to obtain (E)-4-(4-(9H-carbazol-9-yl)styryl)-1-(4-benzoylbenzyl)pyridinium bromide (BKD-Pys-BP), (E)-4-(2-(4'-(9H-carbazol-9-yl)-[1,1'-biphenyl]-4-yl)vinyl)-1-(4-benzoylbenzyl)pyridinium bromide (BKB-Pys-BP) and (E)-4-(2-(5-(4-(9H-carbazol-9-yl)phenyl)thiophen-2-yl)vinyl)-1-(4-benzoylbenzyl)pyridinium bromide (BKT-Pys-BP).

[0142] In step S21 of some preferred embodiments of this patent application, the catalyst selected for the Suzuki reaction is tetrakis(triphenylphosphine)palladium (5%-8% eq), the base used is potassium carbonate (2eq), the boric acid is in excess (1.5eq), and the solvent system used for the reaction is tetrahydrofuran and methanol (volume ratio = 1:1). After refluxing for 24 h in an N 2 atmosphere, the progress of the reaction was monitored by thin-layer chromatography.

[0143] In some preferred embodiments of this patent application, after step S21 is completed, the reaction solution is cooled to room temperature, concentrated under reduced pressure to remove the reaction solution, and the crude product is separated and purified by column chromatography. The eluent used is petroleum ether and ethyl acetate, with a ratio of 50:1, and finally BK-Py is obtained.

[0144] In a more preferred embodiment of this patent application, the specific operating steps of step S21 are as follows:

[0145] 9-(4-bromophenyl)-carbazole (0.96 g, 322.21 g / mol, 3 mmol), 4-pyridineboronic acid (0.55 g, 122.92 g / mol, 4.5 mmol), tetrakis(triphenylphosphine)palladium (Pd(PPh 3 ) 4, 0.21 g, 1155.57 g / mol, 0.18 mmol) and potassium carbonate (K 2 CO 3 , 0.83 g, 138.21 g / mol, 6 mmol) were successively added into a 100 mL two-necked round-bottom flask, and then tetrahydrofuran and methanol were added to the flask in a ratio of 1:1. The reaction was heated to 80 °C in an N 2 atmosphere and reacted for 24 h. After the reaction, the crude product was obtained by concentration under reduced pressure and separated and purified by column chromatography. The eluent was a mixed system of ethyl acetate and petroleum ether (volume ratio = 50:1), and finally a white solid was obtained (yield: 83%).

[0146] The reaction equation is as follows:

[0147]

[0148] As Figure 9 shown in the NMR spectrum, the characterization of the product TPE-Py can be obtained. The NMR data are as follows: 1 H NMR (400 MHz, CDCl 3 ) δ 8.72 (d, J = 5.9 Hz, 2H), 8.16 (d, J = 7.7 Hz, 2H), 7.85 (d, J = 8.5 Hz, 2H), 7.69 (d, J = 8.4 Hz, 2H), 7.58 (dd, J = 4.5, 1.5 Hz, 2H), 7.51 - 7.38 (m, 4H), 7.31 (t, J = 7.0 Hz, 2H).

[0149] In some preferred embodiments of the present patent application, the solvents selected for the Menshutkin reaction in step S22 are dichloromethane, ethanol, and tetrahydrofuran. More preferably, the polar aprotic solvent tetrahydrofuran is used as the reaction solvent to completely dissolve the raw materials, but the solvent should not be in excess, and just enough to dissolve is appropriate.

[0150] In some preferred embodiments of the present patent application, the reaction temperature in step S22 is 80 °C and the reaction time is 24 h.

[0151] In some preferred embodiments of the present patent application, the molar ratio of BK-Py to methyl iodide in step S22 is 1:(1 - 1.05). Considering that methyl iodide is volatile, the molar ratio of 1:(2 - 3) is used for the reaction; while the reaction of BK-Py with benzyl bromide and BP-M-Br is carried out at a molar ratio of 1:(1 - 1.05).

[0152] In some preferred embodiments of the present patent application, after the product in step S22 precipitates inside the flask, it is scraped back into the reaction solution with a spatula to make it react fully.

[0153] In some preferred embodiments of the present patent application, after the reaction in step S22 is completed, the reaction solution is sufficiently cooled, and the product precipitates out in solid form. Then, suction filtration is carried out to collect the filter residue. Subsequently, the crude product is washed with a mixture of n-hexane and tetrahydrofuran in small portions multiple times; more preferably, a centrifuge is used for washing and impurity removal, and finally, the product is obtained by vacuum drying, and the obtained product basically meets the requirements for analysis and testing; more preferably, column chromatography separation can also be carried out using neutral alumina, and the order of the eluents used is dichloromethane, ethyl acetate, and methanol.

[0154] In a more preferred embodiment of the present patent application, the specific operation steps of step S22 are as follows:

[0155] Preparation of BK-Pys-M in step 221

[0156] Dissolve BK-Py (0.16 g, 320.40 g / mol, 0.5 mmol) in 20 mL of tetrahydrofuran. Subsequently, accurately measure methyl iodide (0.21 g, 141.9 g / mol, 1.5 mmol) and add it to the reaction solution. Heat the reaction solution to 80 °C and react for 24 h. After the reaction is completed, filter the precipitate in the reaction solution, and wash the filter residue with a mixture of tetrahydrofuran and n-hexane several times to obtain the crude product. The crude product is separated by column chromatography using neutral alumina, and the order of using the eluent is dichloromethane, ethyl acetate, and methanol. The finally obtained product is a yellow solid (yield: 85%).

[0157] The reaction equation is as follows:

[0158]

[0159] As Figure 10 shown by the 1H NMR and Figure 11 13C NMR spectra, the characterization of compound BK-Pys-M can be obtained. The NMR data of compound BK-Pys-M are as follows: 1 H NMR (600 MHz, dmso) δ 9.09 (d, J = 6.8 Hz, 2H), 8.63 (d, J = 6.7 Hz, 2H), 8.39 (d, J = 8.4 Hz, 2H), 8.29 (d, J = 7.8 Hz, 2H), 7.94 (d, J = 8.1 Hz, 2H), 7.53 (d, J = 8.1 Hz, 2H), 7.49 (t, J = 7.6 Hz, 2H), 7.35 (t, J = 7.3 Hz, 2H), 4.40 (s, 3H). 1313C NMR (151 MHz, dmso) δ 153.67, 146.12, 140.70, 140.02, 132.49, 130.46, 127.69, 126.95, 124.53, 123.61, 121.14, 121.11, 110.22, 47.64。

[0160] Step 222 Preparation of BK-Pys-B

[0161] Dissolve BK-Py (0.16 g, 320.40 g / mol, 0.5 mmol) in 20 mL of tetrahydrofuran. Subsequently, accurately measure benzyl bromide (0.094 g, 171.04 g / mol, 0.55 mmol) and add it to the reaction solution. Then, heat the reaction solution to 80 °C and react for 24 h. After monitoring the completion of the reaction by thin-layer chromatography, filter the precipitate in the reaction solution, and wash the filter residue several times with a mixed solution of tetrahydrofuran and n-hexane to obtain the crude product. The crude product is separated by column chromatography on neutral alumina, and the eluents are used in the order of dichloromethane, ethyl acetate, and methanol. The final product obtained is a yellow-green solid (yield: 86%).

[0162] The reaction equation is as follows:

[0163]

[0164] As Figure 12 shown by the 1H NMR spectrum of Figure 13 and the 13C NMR spectrum of 1 1H NMR (400 MHz, CDCl 3 ) δ 9.55 (d, J = 5.8 Hz, 2H), 8.26 (d, J = 5.4 Hz, 2H), 8.15 (d, J = 7.8 Hz, 2H), 8.00 (d, J = 8.4 Hz, 2H), 7.83 (d, J = 8.3 Hz, 2H), 7.70 (d, J = 7.5 Hz, 2H), 7.50 (d, J = 8.2 Hz, 2H), 7.47–7.42 (m, 5H), 7.34 (t, J = 7.0 Hz, 2H), 6.31 (s, 2H). 13 13C NMR (101 MHz, DMSO) δ 154.58, 145.35, 140.88, 140.03, 136.79, 134.99, 132.50, 130.70, 129.91, 129.76, 129.33, 127.71, 127.00, 125.43, 123.67, 121.20, 110.28, 62.94。

[0165] Step 223 Preparation of BK-Pys-BP

[0166] Dissolve BK-Py (0.16 g, 320.40 g / mol, 0.5 mmol) and BP-M-Br (0.15 g, 275.15 g / mol, 0.55 mmol) in 20 mL of tetrahydrofuran. Then, heat the reaction solution to 80 °C and react for 24 h. A large amount of solid will precipitate during the reaction. After monitoring the reaction by thin-layer chromatography until it is completed, filter the precipitate in the reaction solution, and wash the filter residue several times with a mixed solution of tetrahydrofuran and n-hexane to obtain the crude product. The crude product is separated by neutral alumina column chromatography, and the eluents are used in the order of dichloromethane, ethyl acetate, and methanol. Finally, the product obtained is a yellow-green solid (yield: 87%).

[0167] The reaction equation of this reaction is as follows:

[0168]

[0169] As Figure 14 shown by the 1H NMR spectrum of Figure 15 and the 13C NMR spectrum of 1 H NMR (600 MHz, dmso) δ 9.39 (d, J = 7.0 Hz, 2H), 8.72 (d, J = 7.0 Hz, 2H), 8.41 (d, J = 8.7 Hz, 2H), 8.29 (d, J = 7.7 Hz, 2H), 7.96 (d, J = 8.6 Hz, 2H), 7.84 (d, J = 8.4 Hz, 2H), 7.80 (d, J = 8.3 Hz, 2H), 7.76 (d, J = 7.0 Hz, 2H), 7.71 (t, J = 7.4 Hz, 1H), 7.59 (t, J = 7.8 Hz, 2H), 7.53 (d, J = 8.2 Hz, 2H), 7.49 (t, J = 7.6 Hz, 2H), 7.35 (t, J = 6.9 Hz, 2H), 6.07 (s, 2H). 13 C NMR (151 MHz, dmso) δ 195.69, 154.72, 145.56, 140.92, 140.00, 139.07, 138.16, 137.05, 133.45, 132.41, 130.75, 130.69, 130.12, 129.31, 129.11, 127.68, 126.95, 125.46, 123.65, 121.15, 110.24, 67.45, 62.32.

[0170] In some preferred embodiments of the present patent application, in step S23, the solvent used in the Menshutkin reaction is tetrahydrofuran, the reaction molar ratio of BP-M-Br to 4-methylpyridine is 1:1, the reaction refluxes at 80 °C for 24 h, and the product precipitates in solid form during the reaction.

[0171] In some preferred embodiments of the present patent application, after step S23, since the product has a low melting point and is oily at room temperature, the reaction solution is filtered while it is hot. The oily product on the filter paper is washed with a small amount of n-hexane multiple times, then dissolved in dichloromethane and distilled under reduced pressure to remove dichloromethane as completely as possible, and finally BP-M-Pys is obtained.

[0172] In a more preferred embodiment of the present patent application, the specific operation steps of step S23 are as follows:

[0173] Preparation of BP-M-Pys

[0174] Dissolve BP-M-Br (1.5 g, 275.15 g / mol, 5.5 mmol) and 4-methylpyridine (0.51 g, 93.13 g / mol, 5.5 mmol) in 30 mL of tetrahydrofuran, reflux at 80 °C for 24 h. After monitoring the end of the reaction by thin-layer chromatography, filter the product, wash it with a small amount of n-hexane multiple times, dissolve it in dichloromethane and spin-dry it. The product is a brown oily substance.

[0175] The reaction equation of this reaction is as follows:

[0176]

[0177] As Figure 16 shown by the 1H NMR spectrum, the characterization of the compound BP-M-Pys can be obtained. The 1H NMR data of the compound BP-M-Pys are as follows: 1 H NMR(400MHz,CDCl 3 )δ9.47(d,J=6.6Hz,2H),7.85(t,J=6.9Hz,4H),7.75–7.66(m,4H),7.57(t,J=7.4Hz,1H),7.44(t,J=7.7Hz,2H),6.36(s,2H),2.61(s,3H).

[0178] In some preferred embodiments of the present patent application, in step S24, the catalyst selected for the Suzuki reaction is tetrakis(triphenylphosphine)palladium (5%-8% eq), the base used is potassium carbonate (2 eq). Due to the influence of the side reaction of boric acid self-coupling, 4-formylphenylboronic acid should be in excess (1.5 eq). The solvent system used in this reaction is tetrahydrofuran and methanol (1:1). After the reaction refluxes in a N2 atmosphere for 24 h, monitor the reaction process by thin-layer chromatography.

[0179] In some preferred embodiments of this patent application, after step S24 ends, the reaction solution is cooled to room temperature. After removing the reaction solution by reduced pressure concentration, the crude product is separated and purified by column chromatography. The eluent used is petroleum ether and ethyl acetate, and the ratio is 100:1. Finally, BKD-CHO is obtained.

[0180] In a more preferred embodiment of this patent application, the specific operation steps of step S24 are as follows:

[0181] Preparation of BKB-CHO

[0182] 9-(4-Bromophenyl)-carbazole (0.96 g, 322.21 g / mol, 3 mmol), 4-formylphenylboronic acid (0.67 g, 149.94 g / mol, 4.5 mmol), tetrakis(triphenylphosphine)palladium (Pd(PPh 3 ) 4 , 0.21 g, 1155.57 g / mol, 0.18 mmol) and potassium carbonate (K 2 CO 3 , 0.83 g, 138.21 g / mol, 6 mmol) are successively added to a 100 mL two-necked round-bottom flask. Then, tetrahydrofuran and methanol are added to the flask in a ratio of 1:1. This reaction is heated to 80 °C in an N 2 atmosphere and reacted for 24 h. After the reaction ends, the crude product is obtained by reduced pressure concentration and separated and purified by column chromatography. The eluent is ethyl acetate:petroleum ether volume ratio = 100:1. Finally, a white solid is obtained (yield: 80%).

[0183] The reaction equation is as follows:

[0184]

[0185] As Figure 17 shown in the NMR spectrum of, the characterization of compound BKB-CHO can be obtained. The NMR data are: 1 H NMR (400 MHz, CDCl 3 ) δ 10.09 (s, 1H), 8.16 (d, J = 7.7 Hz, 2H), 8.01 (d, J = 8.3 Hz, 2H), 7.86 (dd, J = 8.2, 6.0 Hz, 4H), 7.69 (d, J = 8.5 Hz, 2H), 7.51 - 7.38 (m, 4H), 7.31 (t, J = 7.4 Hz, 2H).

[0186] In some preferred embodiments of the present patent application, in step S25, the catalyst selected for the Suzuki reaction is tetrakis(triphenylphosphine)palladium (5%-8% eq), the base used is potassium carbonate (2 eq), 5-formyl-2-thiopheneboronic acid should be in excess (1.5 eq), and the solvent system used is tetrahydrofuran and methanol (1:1).

[0187] In some preferred embodiments of the present patent application, in step S25, since the reaction involves a heterocyclic thiophene group, the reaction conversion rate will decrease. Therefore, the reaction conditions are optimized to reflux for 48 h, and the reaction process is monitored by thin-layer chromatography.

[0188] In some preferred embodiments of the present patent application, after step S25 is completed, the reaction solution is cooled to room temperature, and after removing the reaction solution by concentration under reduced pressure, the crude product is separated and purified by column chromatography. The eluent used is petroleum ether and ethyl acetate, and the volume ratio is 100:1. Finally, BKT-CHO is obtained.

[0189] In a more preferred embodiment of the present patent application, the specific operation steps of step S25 are as follows:

[0190] Preparation of BKT-CHO

[0191] 9-(4-Bromophenyl)-carbazole (0.96 g, 322.21 g / mol, 3 mmol), 5-formyl-2-thiopheneboronic acid (0.71 g, 155.97 g / mol, 4.5 mmol), tetrakis(triphenylphosphine)palladium (Pd(PPh 3)4 , 0.21 g, 1155.57 g / mol, 0.18 mmol) and potassium carbonate (K 2 CO 3 , 0.83 g, 138.21 g / mol, 6 mmol) are successively added to a 100 mL two-necked round-bottom flask, and then tetrahydrofuran and methanol are added to the flask in a ratio of 1:1. The reaction is heated to 80 °C in an N 2 atmosphere and reacted for 48 h. After the reaction is completed, the crude product is obtained by concentration under reduced pressure, and is separated and purified by column chromatography. The eluent is ethyl acetate:petroleum ether = 100:1, and finally a white solid is obtained (yield: 35%).

[0192] The reaction equation is as follows:

[0193]

[0194] As Figure 18 shown, by testing and characterizing the nuclear magnetic resonance spectrum of the product obtained from the reaction in step 25, it can be known that the compound BKT-CHO has been obtained. The nuclear magnetic data is: 1 H NMR (400 MHz, CDCl 3)δ9.93(s,1H),8.15(d,J=7.7Hz,2H),7.90(d,J=8.5Hz,2H),7.79(d,J=3.9Hz,1H),7.66(d,J=8.5Hz,2H),7.51-7.40(m,5H),7.35-7.28(m,2H).

[0195] In some preferred embodiments of the present patent application, since the reaction in step S26 belongs to a dehydration condensation reaction, anhydrous organic solvents with extremely low water content are preferably used as much as possible, so that the reaction equilibrium shifts to the right during the reaction. Therefore, dry ethanol is used for the reaction.

[0196] In some preferred embodiments of the present patent application, in step S26, due to solubility problems, a mixed system of dichloromethane and dry ethanol is used, and piperidine is used as a base for catalysis in the reaction.

[0197] In some preferred embodiments of the present patent application, after step S26 is completed, the reaction solution is cooled to room temperature, and after the reaction solution is removed by concentration under reduced pressure, the crude product is separated and purified by column chromatography. Therefore, neutral alumina is used for column separation, and the eluents are used in the order of dichloromethane, ethyl acetate, and methanol. Finally, BKD-Pys-BP, BKB-Pys-BP, and BKT-Pys-BP are obtained.

[0198] In a more preferred embodiment of the present patent application, the specific operation steps of step S26 are as follows:

[0199] Step 261 Preparation of BKD-Pys-BP

[0200] N-(4-formylphenyl)carbazole (0.30 g, 271.32 g / mol, 1.1 mmol) and BP-M-Pys (0.37 g, 368.27 g / mol, 1 mmol) are added to a 50 mL round-bottom flask and dissolved in 30 mL (10 + 20) of a dry dichloromethane and ethanol mixture. Then, two drops of piperidine are added dropwise to the reaction solution, and the reaction is carried out at 80 °C for 48 h. After the reaction is completed, it is cooled to room temperature, and after the reaction solution is concentrated under reduced pressure, it is separated by column chromatography on neutral alumina. The eluents are used in the order of dichloromethane, ethyl acetate, and methanol. The product is an orange solid (yield: 43%).

[0201] The reaction equation is as follows:

[0202]

[0203] As Figure 19 shown by the 1H NMR spectrum of 11H NMR (400 MHz, CDCl 3 ) δ 9.28 (d, J = 5.6 Hz, 2H), 8.23 (d, J = 5.7 Hz, 2H), 8.14 (d, J = 7.7 Hz, 2H), 8.03 (d, J = 16.2 Hz, 1H), 7.93 (d, J = 8.3 Hz, 2H), 7.88 - 7.73 (m, 6H), 7.66 (d, J = 8.3 Hz, 2H), 7.61 (t, J = 7.4 Hz, 1H), 7.52–7.45 (m, 4H), 7.44 (s, 2H), 7.31 (t, J = 7.5 Hz, 3H), 6.27 (s, 2H). 13 13C NMR (101 MHz, CDCl 3 ) δ 195.84, 153.93, 144.44, 141.86, 140.20, 138.88, 137.21, 136.78, 133.16, 133.00, 131.56, 131.04, 130.11, 129.38, 128.50, 127.10, 126.19, 125.30, 124.52, 123.76, 122.50, 120.56, 120.46, 109.79, 44.61.

[0204] Step 262 Preparation of BKB-Pys-BP

[0205] BKB-CHO (0.38 g, 347.42 g / mol, 1.1 mmol) and BP-M-Pys (0.37 g, 368.27 g / mol, 1 mmol) were added into a 50 mL round-bottom flask and dissolved in 30 mL of a dry dichloromethane and ethanol mixture (10 + 20). Then two drops of piperidine were added to the reaction solution, and the reaction was carried out at 80 °C for 48 h. After the reaction, it was cooled to room temperature. After concentrating the reaction solution under reduced pressure, it was separated by column chromatography on neutral alumina. The eluents were used in the following order: dichloromethane, ethyl acetate, and methanol. The product was a red solid (yield: 47%).

[0206] The reaction equation is as follows:

[0207]

[0208] As Figure 21 shown by the 1H NMR spectrum of 22 and the 13C spectrum of 22, the characterization of compound BKB-Pys-BP can be obtained. The NMR data of compound BKB-Pys-BP are as follows: 11H NMR (400 MHz, DMSO) δ 9.18 (d, J = 6.6 Hz, 2H), 8.36 (d, J = 6.6 Hz, 2H), 8.28 (d, J = 7.8 Hz, 2H), 8.17 (d, J = 16.3 Hz, 1H), 8.08 (d, J = 8.4 Hz, 2H), 7.96 (q, J = 8.4 Hz, 4H), 7.83 (d, J = 8.2 Hz, 21H), 7.79 - 7.69 (m, 8H), 7.58 (t, J = 7.6 Hz, 2H), 7.48 (d, J = 3.2 Hz, 4H), 7.36 - 7.29 (m, 2H), 5.94 (s, 1H). 13 13C NMR (101 MHz, DMSO) δ 195.74, 153.93, 152.17, 145.10, 141.48, 141.33, 140.45, 139.29, 138.53, 138.08, 137.19, 137.10, 135.03, 133.50, 130.79, 130.17, 129.54, 129.15, 128.90, 127.86, 127.58, 126.82, 124.83, 123.94, 123.33, 121.09, 120.70, 110.18, 25.60。

[0209] Preparation of 263BKT - Pys - BP

[0210] BKT - CHO (0.39 g, 353.44 g / mol, 1.1 mmol) and BP - M - Pys (0.37 g, 368.27 g / mol, 1 mmol) were added into a 50 mL round - bottom flask and dissolved in 30 mL of a mixed solution of dry dichloromethane and ethanol (10 + 20). Then two drops of piperidine were added dropwise into the reaction solution, and the reaction was carried out at 80 °C for 48 h. After the reaction was completed, it was cooled to room temperature. After concentrating the reaction solution under reduced pressure, it was separated by column chromatography on neutral alumina. The eluents were used in the following order: dichloromethane, ethyl acetate, and methanol. The product was an orange solid (yield: 30%).

[0211] The reaction equation is as follows:

[0212]

[0213] As Figure 23 shown by the 1H NMR spectrum of 1 1H NMR (400 MHz, CDCl 3)δ9.23(d, J = 5.5 Hz, 2H), 8.13(d, J = 7.7 Hz, 2H), 8.08 - 8.01(m, 3H), 7.81 - 7.72(m, 8H), 7.57(d, J = 7.0 Hz, 3H), 7.52 - 7.39(m, 7H), 7.37(d, J = 7.1 Hz, 1H), 7.30(d, J = 7.8 Hz, 2H), 6.84(d, J = 15.8 Hz, 1H), 6.24(s, 2H). 13 C NMR(101 MHz, CDCl 3 )δ195.84, 153.55, 148.18, 144.14, 140.42, 139.77, 138.73, 138.10, 137.49, 136.78, 135.56, 134.71, 132.92, 132.02, 130.99, 130.11, 129.33, 128.47, 127.38, 127.34, 126.11, 125.05, 123.76, 123.59, 120.56, 120.43, 120.33, 109.72, 44.55。

[0214] A series of preparation methods of pyridinium organic photosensitizers with tetraphenylethylene pyridinium salt or N - phenylcarbazole as the core and methods for improving the efficiency of reactive oxygen species generation provided by this patent application are organic pyridinium small molecules prepared by using classical reactions such as NBS bromination reaction, Suzuki coupling and Menshutkin. By designing a Donor - Accept (D - A) system, the separation degree of the HOMO - LUMO orbitals is increased, which is beneficial to reducing ΔEst; the introduction of benzophenone further improves the intersystem crossing rate, enabling more excited - state energy to transfer to the triplet state, and then promoting the efficient generation of reactive oxygen species. This design strategy can greatly improve the reactive oxygen species generation ability of the photosensitizer and can be used for application research in aspects such as photodynamic therapy.

[0215] In addition, the pyridinium organic photosensitizers provided by this patent application can be used as photosensitizer materials for photodynamic therapy. By utilizing the hydrophilic characteristics of N + ions and the electrostatic interaction with some subcellular structures to achieve targeting, they have high targeting ability, can achieve efficient photodynamic therapy, and have good application prospects.

[0216] Performance Test

[0217] Taking the compounds TPE - Py, TPE - Pys - M, TPE - Pys - B and TPE - Pys - BP prepared in steps S12 and S13 as test objects, the test results are as Figures 25 to 27 shown.

[0218] Figure 25 Figure (a) shows the absorption spectra of compounds TPE-Py, TPE-Pys-M, TPE-Pys-B, and TPE-Pys-BP in solution state measured by Shimadzu UV-2700 UV-Visible Spectrophotometer, with a concentration of 1×10 -5 mol / L. From the UV-visible spectral analysis, it can be seen that after converting pyridine to pyridinium salt, due to the enhanced D-A intensity in the molecular system, the wavelength undergoes an obvious red shift. Figure 25 Figure (b) shows the fluorescence emission spectra of compounds TPE-Py, TPE-Pys-M, TPE-Pys-B, and TPE-Pys-BP in solid state measured by Edinburgh FLS980. The excitations are 323 nm, 366 nm, 372 nm, and 374 nm respectively.

[0219] Figure 26 Figure shows the aggregation-induced emission (AIE) characteristic curves of compounds TPE-Py, TPE-Pys-M, TPE-Pys-B, and TPE-Pys-BP measured by Edinburgh FLS980. The concentration of the test solution is 1×10 -5 mol / L, and the selected solvent system is dichloromethane and n-hexane. As Figure 26 can be seen, all four compounds have typical AIE characteristics. As a typical propeller-shaped compound, tetraphenylethylene shows restricted intramolecular motion due to aggregation in a poor solvent environment, thus increasing its radiative transition pathway and exhibiting strong fluorescence emission in the aggregated state.

[0220] Figure 27 Figure shows the test of reactive oxygen species (ROS) generation level. In this test, 2,7-dichlorodihydrofluorescein diacetate (DCFH) is selected as the ROS generation indicator (1×10 -5 mol / L), and the ROS generation ability of TPE-Py, TPE-Pys-M, TPE-Pys-B, and TPE-Pys-BP (concentration: 1×10 -6 mol / L) is tested under different illumination times (0 s, 15 s, 30 s, 45 s, 60 s, 75 s, 90 s, 120 s, 150 s, 180 s). The principle of this test is that DCFH itself has no fluorescence, and this compound can be rapidly oxidized by ROS (phenol is oxidized to quinone structure), thus generating a strong fluorescent product 2',7'-dichlorofluorescein (DCF). The change in fluorescence intensity at 525 nm can be detected in real time by a fluorescence spectrometer. The higher the fluorescence intensity, the more ROS are generated.

[0221] From Figure 27It can be seen that the levels of reactive oxygen species generation of TPE-Py, TPE-Pys-M, and TPE-Pys-B are almost negligible; while when the benzophenone structure is introduced, the level of reactive oxygen species of TPE-Pys-BP increases significantly, exceeding that of the commercial Rose Bengal (RB), and there is no benzophenone structure in the RB molecular structure. Therefore, this design strategy can be used as a method for enhancing reactive oxygen species, which provides a reference for the preparation of highly efficient reactive oxygen species-generating photosensitizers and can be applied to the field of photodynamic therapy.

[0222] Taking the compounds BK-Py, BK-Pys-M, BK-Pys-B, BK-Pys-BP, BKD-Pys-BP, BKB-Pys-BP, and BKT-Pys-BP prepared in Step 21, Step 22, and Step 26 as test objects, the test results are as Figures 28 to 30 shown.

[0223] Figure 28 (a) of is the ultraviolet absorption spectra of BK-Py, BK-Pys-M, BK-Pys-B, BK-Pys-BP, BKD-Pys-BP, BKB-Pys-BP, and BKT-Pys-BP in the solution (DMSO) state, with a concentration of 1×10 -5 mol / L. It can be seen from the ultraviolet absorption that with the increase of the D-A intensity and conjugation degree of the system, the ultraviolet absorption shows an obvious red shift. Figure 28 (b) of is the fluorescence spectrum of the solid compound, and the excitations are: 323 nm, 376 nm, 385 nm, 387 nm, 408 nm, 392 nm, and 443 nm respectively. The spectral distribution also indicates that the system has synthesized a fluorescent material with spectral emission in the full visible region (400 - 685 nm).

[0224] Figure 29 (a) and (b) of are the aggregation-induced emission (AIE) characteristic curves of the compounds BK-Py, BK-Pys-M, BK-Pys-B, BK-Pys-BP, BKD-Pys-BP, BKB-Pys-BP, and BKT-Pys-BP obtained by Edinburgh FLS980 test. The concentration of the test solution is 1×10 -5 mol / L, and the selected solvent system is dichloromethane and n-hexane. From Figure 29 it can be seen that after modifying BK-Py into pyridinium salt, the transformation from ACQ to AIE properties is successfully achieved.

[0225] Figure 30 For the test of the level of reactive oxygen species generation, Figure 30 (a) of uses DCFH as the reactive oxygen species generation indicator for this test (1×10 -5mol / L), the ability of BK-Py, BK-Pys-M, BK-Pys-B, BK-Pys-BP, BKD-Pys-BP, BKB-Pys-BP and BKT-Pys-BP (concentration: 1×10 -6 mol / L) to generate reactive oxygen species was tested under different light exposure times (0 s, 15 s, 30 s, 45 s, 60 s, 75 s, 90 s, 120 s, 150 s, 180 s). As can be seen from Figure 30 a of, with the introduction of benzophenone, there is a transformation of reactive oxygen species from non-existent to existent. From Figure 30 b of, by comparing the ability of BKD-Pys-BP, BKB-Pys-BP and BKT-Pys-BP to generate reactive oxygen species, it can also be concluded that with the introduction of thiophene, the ability to generate reactive oxygen species is greatly enhanced, which can be used as an efficient photosensitizer in the integrated application of tumor diagnosis and treatment.

[0226] The preparation of a series of tetraphenylethylene pyridinium salts and pyridinium salt compounds with N-phenylcarbazole as the core provided by this patent application and the method for improving the efficiency of reactive oxygen species generation are organic pyridinium salt small molecules prepared by using classical reactions such as NBS bromination reaction, Suzuki coupling and Menshutkin. By designing a Donor-Accept (D-A) system, the separation degree of the HOMO-LOMO orbitals is increased, which is beneficial to reducing ΔEst; the introduction of benzophenone further improves the intersystem crossing rate, enabling more excited state energy to transfer to the triplet state, thereby promoting the efficient generation of reactive oxygen species. This design strategy can greatly improve the ability of the photosensitizer to generate reactive oxygen species and can be used in the applied research of photodynamic therapy and other aspects.

[0227] In the description of this specification, the description with reference to terms such as "one embodiment", "some embodiments", "schematic embodiments", "examples", "specific examples", or "some examples" means that the specific features, structures, materials or characteristics described in connection with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic expressions of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in a suitable manner in any one or more embodiments or examples.

[0228] Although several embodiments of this patent application have been shown and described, those of ordinary skill in the art can understand that various changes, modifications, substitutions and variations can be made to these embodiments without departing from the principles and purposes of the present invention, and the scope of the present invention is defined by the claims and their equivalents.

Claims

1. An organic photosensitizer of pyridinium salt Characterized in that The organic photosensitizer of pyridinium salt is a pyridinium salt based on tetraphenylethylene and has the molecular structure shown below:

2. A preparation method of the organic photosensitizer of pyridinium salt according to claim 1 Characterized in that It includes the following steps: S11. Preparation of intermediate 4-bromomethyl benzophenone (BP-M-Br) 4-Methyl benzophenone and N-bromosuccinimide (NBS) are irradiated by a high-pressure mercury lamp, and the NBS bromination reaction is initiated by benzoyl peroxide (BPO) to obtain 4-bromomethyl benzophenone (BP-M-Br) with bromine substitution at the benzyl position; S12. Preparation of 4-(4-(1,2,2-triphenylvinyl)phenyl)pyridine (TPE-Py) Using the Suzuki coupling reaction, 1-(4-bromophenyl)-1,2,2-triphenylethylene, 4-pyridineboronic acid, potassium carbonate and tetrakis(triphenylphosphine)palladium are dissolved in a mixed system of tetrahydrofuran and methanol, and reacted at 80 °C under N 2 protection to prepare 4-(4-(1,2,2-triphenylethenyl)phenyl)pyridine (TPE-Py); S13. Preparation of the final product TPE-Pys-BP Using the Menschutkin reaction, the product TPE-Py obtained in step S12 and the product BP-M-Br in step S11 are refluxed in tetrahydrofuran to obtain 1-(4-benzoylbenzyl)-4-(4-(1,2,2-triphenylvinyl)phenyl)pyridinium-1-bromide (TPE-Pys-BP).

3. The preparation method of the organic photosensitizer of pyridinium salt according to claim 2 Characterized in that The NBS bromination in step S11 requires protection by an inert gas, and the reaction time is 3 to 6 hours.

4. The preparation method of the organic photosensitizer of pyridinium salt according to claim 2 Characterized in that The solvent used in the step S12 is tetrahydrofuran and methanol, and the volume ratio of the two is 1:

1. The catalyst used is Pd(PPh 3 ) 4 .

5. An organic photosensitizer for photodynamic therapy Characterized in that The organic photosensitizer uses the organic photosensitizer of pyridinium salt as described in claim 1.

Images