Synthesis method and application of a new photosensitizer

Abstract

The present invention discloses a synthesis method and application of a novel photosensitizer. The photosensitizer has the following structure: #imgabs0#, wherein the substituent R is selected from any one of bromine, N,N-dimethylaminophenyl, and p-cyanophenyl. This photosensitizer is prepared from indole derivatives and pyrrole-2-carboxaldehyde derivatives via piperidine- and acetic acid-catalyzed condensation followed by coupling with phenylboronic acid. The synthesis method is simple, separation and purification are convenient, and the yield is high. The introduction of aromatic rings via a cross-coupling reaction increases the molecular conjugation, red-shifts the absorption and emission spectra, and promotes the generation of singlet oxygen.

Description

Technical Field

[0001] The present invention relates to a synthesis method and application of a photosensitizer, and more specifically, to a synthesis method and application of a novel photosensitizer. Background Art

[0002] Compared to fluorescein, rhodamine, or cyanine dyes, boron dipyrrole fluoride fluorescent dyes offer advantages such as higher selectivity, higher sensitivity, excellent optical stability, and pH insensitivity, making them widely used in biomarkers, fluorescent probes, and bioimaging. The introduction of bromine atoms into the boron dipyrrole fluoride fluorescent dyes of the present invention results in a lower fluorescence quantum yield and a larger molar extinction coefficient, making them suitable for reactive oxygen species detection and fluorescence imaging. Photodynamic therapy (PDT) has become an effective alternative for cancer treatment, as PDT can achieve controlled ablation of tumor cells by modulating incident light. Photosensitizers, particularly those based on organic fluorescent compounds, play a crucial role in PDT's efficacy. Not only can photosensitizers be activated by light to harvest toxic reactive oxygen species to degrade tumors or cancerous masses, but their fluorescence signals can also be used to dynamically monitor tumor status. Traditional organic fluorescent photosensitizers, such as porphyrin derivatives and phthalocyanine derivatives, often have low tumor specificity, and nonspecific uptake in normal tissues can lead to unwanted side effects. Therefore, the development of fluorescent molecules with low side effects and high singlet oxygen generation efficiency is highly desirable. To address the above problems, the present invention discloses a method for synthesizing and applying a photosensitizer, which can generate singlet oxygen in living cells, thereby killing cancerous tumors, and has the advantages of being easy to detect, sensitive, and having a wide detection range. Summary of the Invention

[0003] The main purpose of the present invention is to provide a synthesis method and application of a photosensitizer.

[0004] The technical solutions of the present invention are as follows:

[0005] A synthesis method and application of a photosensitizer, the chemical structure of the compound is:

[0006]

[0007] Wherein, the substituent R is any one selected from bromine, N,N-dimethylaminophenyl, and p-cyanophenyl. As a preferred embodiment, the chemical structure of the compound is:

[0008]

[0009] Any one of .

[0010] The synthesis method and application of the photosensitizer include the following synthesis path:

[0011]

[0012] The method comprises the following steps:

[0013] (1) Add compound 1 and toluene or DMF to a reaction flask at room temperature, stir to dissolve, then add compound 2, piperidine, and acetic acid, and heat under reflux to obtain a reaction solution;

[0014] (2) The reaction solution in step (1) was subjected to rotary evaporation and then separated by silica gel column chromatography to obtain product I-1.

[0015] (3) adding 1,4-dioxane and compound 3 to compound I-1 in step (2), stirring and dissolving, then adding tetrakistriphenylphosphine palladium or bis(triphenylphosphine)palladium dichloride or palladium acetate, and potassium hydroxide aqueous solution, heating to obtain a reaction solution;

[0016] (4) The reaction solution in step (3) is washed with water, extracted, dried, concentrated, and purified to obtain product I, a new photosensitizer.

[0017] Compound 1 is an indole derivative, and compound 2 is a derivative of pyrrole-2-carboxaldehyde; the feeding molar ratio of compound 1 to compound 2 is 1:1-10.

[0018] The order of adding the materials in step (1) is compound 1, toluene or DMF, compound 2, piperidine, and acetic acid. Piperidine and acetic acid both act as activating reactants and need to be added last. The feeding ratio of compound 1 to piperidine is 1:1-10; the feeding ratio of compound 1 to acetic acid is 1:1-10.

[0019] The heating temperature of step (1) is 30 to 150° C., and the heating time is 2 to 18 hours.

[0020] The order of adding the materials in step (3) is as follows: compound I-1, 1,4-dioxane, compound 3, then tetrakistriphenylphosphine palladium or bis(triphenylphosphine)palladium dichloride or palladium acetate, and potassium hydroxide aqueous solution. The feeding ratio of compound I-1, compound 3, and tetrakistriphenylphosphine palladium is 1:1-10:0.01-1.

[0021] The pH value of the potassium hydroxide aqueous solution is adjusted to a weak alkalinity of 7-8. The reaction requires an alkaline environment, and the base reacts with the arylboronic acid to generate a tetravalent borate intermediate species.

[0022] The heating temperature of step (3) is 30 to 120° C., and the heating time is 0.5 to 24 hours.

[0023] The beneficial effects of the present invention are as follows:

[0024] (1) The compound of the present invention is an ideal photosensitizer for the further study of B16 cell tumors.

[0025] (2) The synthesis method and application of the photosensitizer described in the present invention are simple, have strong penetrating ability, and can be used for photodynamic therapy.

[0026] (3) The synthesis reaction conditions of the present invention adopt a new catalyst, wherein the catalyst can be tetrakistriphenylphosphine palladium or bis(triphenylphosphine)palladium dichloride or palladium acetate. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 This is a spectrum of compound I-1 obtained in Example 1.

[0028] Figure 2 This is a spectrum of compound I-2 obtained in Example 1.

[0029] Figure 3 This is a spectrum of compound I-3 obtained in Example 11.

[0030] Figure 4 This is a graph showing the cell viability of compounds I-1, I-2, and I-3 obtained in Examples 12-18. DETAILED DESCRIPTION

[0031] The present invention is further described below with reference to the following examples. However, the scope of protection claimed in the present invention is not limited to the scope described in the examples.

[0032] Example 1

[0033] Compound 1 2,3,3-trimethylindole (159 mg, 1 mmol) was weighed and dissolved in 30.00 mL of toluene. 4-bromopyrrole-2-carboxaldehyde (172 mg, 1 mmol), piperidine (0.09 mL, 1 mmol), and acetic acid (0.06 mL, 1 mmol) were added in sequence. The mixture was heated and stirred at 90°C for 8 hours until the reaction was complete. The reactant was rotary evaporated and purified by column chromatography to obtain an orange solid I-1 (165.7 mg) with a yield of 35.4%. Weigh compound I-1 (100 mg, 0.21 mmol), take 6 mL of 1,4-dioxane and dissolve it in a mixture, then add 4-diphenylaminophenylboronic acid (60.7 mg, 0.21 mmol), tetrakistriphenylphosphine palladium (2.43 mg, 0.0021 mmol), and potassium hydroxide aqueous solution (potassium hydroxide 23.5 mg, 0.42 mmol, deionized water 210 μL) in sequence. Heat and stir at 60°C for 8 hours until the reaction is complete. Wash the reactant with water, dry it, and purify it by column chromatography to obtain an orange solid I-2 (50.3 mg) with a yield of 37.8%.

[0034] Example 2

[0035] Compound 1, 2,3,3-trimethylindole (159 mg, 1 mmol), was dissolved in 30.00 mL of toluene. 4-bromopyrrole-2-carboxaldehyde (344 mg, 2 mmol), piperidine (0.09 mL, 1 mmol), and acetic acid (0.06 mL, 1 mmol) were then added sequentially. The mixture was heated at 90°C with stirring for 8 hours until the reaction was complete. The reactants were rotary evaporated and purified by column chromatography to afford I-1 (270.0 mg), an orange solid, with a yield of 57.7%. When the amount of 4-bromopyrrole-2-carboxaldehyde was doubled compared to Example 1, the yield increased by 22.3%. Compound I-1 (100 mg, 0.21 mmol) was weighed and dissolved in 6 mL of 1,4-dioxane. Then, 4-diphenylaminophenylboronic acid (121.4 mg, 0.42 mmol), tetrakistriphenylphosphine palladium (2.43 mg, 0.0021 mmol), and a potassium hydroxide aqueous solution (23.5 mg, 0.42 mmol, 210 μL of deionized water) were added sequentially. The mixture was heated and stirred at 60°C for 8 hours until the reaction was complete. The reactants were washed with water, dried, and purified by column chromatography to obtain an orange solid I-2 (78.7 mg) with a yield of 59.1%. When the amount of 4-diphenylaminophenylboronic acid was doubled compared to Example 1, the yield increased by 21.3%.

[0036] Example 3

[0037] Compound 1 (2,3,3-trimethylindole) (159 mg, 1 mmol) was weighed and dissolved in 30.00 mL of toluene. 4-bromopyrrole-2-carboxaldehyde (172 mg, 1 mmol), piperidine (0.18 mL, 2 mmol), and acetic acid (0.12 mL, 2 mmol) were then added sequentially. The mixture was heated and stirred at 90°C for 8 hours until complete reaction. The reactants were rotary evaporated and purified by column chromatography to obtain an orange solid (178.3 mg) of I-1 (38.1% yield). When the amounts of piperidine and acetic acid were doubled compared to Example 1, the yield remained unchanged. Compound I-1 (100 mg, 0.21 mmol) was weighed and dissolved in 6 mL of 1,4-dioxane. Then, 4-diphenylaminophenylboronic acid (60.7 mg, 0.21 mmol), tetrakistriphenylphosphine palladium (2.43 mg, 0.0021 mmol), and a potassium hydroxide aqueous solution (23.5 mg, 0.42 mmol, 210 μL of deionized water) were added sequentially. The mixture was heated and stirred at 90°C for 6 hours until the reaction was complete. The reactants were washed with water, dried, and purified by column chromatography to obtain an orange solid I-2 (85.5 mg) with a yield of 64.2%. When the reaction temperature was increased by 30°C relative to Example 1, the reaction time was reduced by 2 hours, resulting in a 26.4% increase in yield.

[0038] Example 4

[0039] Compound 1 (2,3,3-trimethylindole) (159 mg, 1 mmol) was weighed and dissolved in 30.00 mL of toluene. 4-bromopyrrole-2-carboxaldehyde (172 mg, 1 mmol), piperidine (0.09 mL, 1 mmol), and acetic acid (0.06 mL, 1 mmol) were then added sequentially. The mixture was heated and stirred at 120°C for 6 hours until the reaction was complete. The reactants were rotary evaporated and purified by column chromatography to obtain an orange solid (303.7 mg) of I-1 (64.9% yield). When the reaction temperature was increased by 30°C relative to Example 1, the reaction time was reduced by 2 hours, and the yield increased by 29.5%. Compound I-1 (100 mg, 0.21 mmol) was weighed and dissolved in 6 mL of 1,4-dioxane. Then, 4-diphenylaminophenylboronic acid (60.7 mg, 0.21 mmol), tetrakistriphenylphosphine palladium (4.86 mg, 0.0042 mmol), and a potassium hydroxide aqueous solution (23.5 mg, 0.42 mmol, 210 μL of deionized water) were added sequentially. The mixture was heated and stirred at 60° C. for 8 hours until the reaction was complete. The reactants were washed with water, dried, and purified by column chromatography to obtain an orange solid I-2 (60.0 mg) with a yield of 45.1%. When the amount of tetrakistriphenylphosphine palladium was doubled compared to Example 1, the yield increased by 7.3%.

[0040] Example 5

[0041] Compound 1 (2,3,3-trimethylindole) (159 mg, 1 mmol) was weighed and dissolved in 30.00 mL of toluene. 4-bromopyrrole-2-carboxaldehyde (172 mg, 1 mmol), piperidine (0.09 mL, 1 mmol), and acetic acid (0.06 mL, 1 mmol) were then added sequentially. The mixture was heated and stirred at 140°C for 6 hours until the reaction was complete. The reactants were rotary evaporated and purified by column chromatography to obtain an orange solid (131 mg) of I-1 (28.0% yield). When the reaction temperature was increased by 30°C and the reaction time was reduced by 2 hours relative to Example 1, the yield decreased by 7.4%. Compound I-1 (100 mg, 0.21 mmol) was weighed and dissolved in 6 mL of 1,4-dioxane. Then, 4-diphenylaminophenylboronic acid (60.7 mg, 0.21 mmol), tetrakistriphenylphosphine palladium (2.43 mg, 0.0021 mmol), and a potassium hydroxide aqueous solution (47.0 mg, 0.84 mmol, 210 μL of deionized water) were added sequentially. The mixture was heated and stirred at 60° C. for 8 hours until the reaction was complete. The reactants were washed with water, dried, and purified by column chromatography to obtain an orange solid I-2 (30.0 mg) with a yield of 22.5%. When the amount of potassium hydroxide was doubled compared to Example 1, that is, when the concentration of the potassium hydroxide aqueous solution was doubled compared to Example 1, the yield decreased by 15.3%.

[0042] Example 6

[0043] Compound 1 (2,3,3-trimethylindole) (159 mg, 1 mmol) was weighed and dissolved in 30.00 mL of toluene. 4-bromopyrrole-2-carboxaldehyde (172 mg, 1 mmol), piperidine (0.09 mL, 1 mmol), and acetic acid (0.06 mL, 1 mmol) were then added sequentially. The mixture was heated and stirred at 60°C for 12 hours until the reaction was complete. The reactants were rotary evaporated and purified by column chromatography to obtain an orange solid (105.8 mg) of I-1 (22.6% yield). When the reaction temperature was reduced by 30°C and the reaction time was increased by 4 hours compared to Example 1, the yield decreased by 12.8%. Compound I-1 (100 mg, 0.21 mmol) was weighed and dissolved in 12 mL of 1,4-dioxane. 4-Diphenylaminophenylboronic acid (60.7 mg, 0.21 mmol), tetrakistriphenylphosphine palladium (2.43 mg, 0.0021 mmol), and a potassium hydroxide aqueous solution (23.5 mg, 0.42 mmol, 210 μL of deionized water) were then added sequentially. The mixture was stirred and heated at 60°C for 8 hours until the reaction was complete. The reactants were washed with water, dried, and purified by column chromatography to obtain an orange solid I-2 (45.8 mg) with a yield of 34.4%. When the amount of 1,4-dioxane was doubled compared to Example 1, the yield did not change significantly.

[0044] Example 7

[0045] Compound 1 (2,3,3-trimethylindole) (159 mg, 1 mmol) was weighed and dissolved in 60.00 mL of toluene. 4-bromopyrrole-2-carboxaldehyde (172 mg, 1 mmol), piperidine (0.09 mL, 1 mmol), and acetic acid (0.06 mL, 1 mmol) were then added sequentially. The mixture was heated and stirred at 90°C for 8 hours until complete reaction. The reactants were rotary evaporated and purified by column chromatography to obtain an orange solid (157.7 mg) of I-1 (33.7% yield). When the amount of toluene was doubled compared to Example 1, the yield did not change significantly. Compound I-1 (100 mg, 0.21 mmol) was weighed and dissolved in 6 mL of 1,4-dioxane. Then, 4-diphenylaminophenylboronic acid (60.7 mg, 0.21 mmol), tetrakistriphenylphosphine palladium (2.43 mg, 0.0021 mmol), and a potassium hydroxide aqueous solution (23.50 mg, 0.42 mmol, 210 μL of deionized water) were added sequentially. The mixture was heated and stirred at 30°C for 16 hours until the reaction was complete. The reactants were washed with water, dried, and purified by column chromatography to obtain an orange solid I-2 (15.8 mg) with a yield of 11.9%. When the reaction temperature was reduced by 30°C and the reaction time was increased by 8 hours compared to Example 1, the yield decreased by 25.9%.

[0046] Example 8

[0047] Compound 1 2,3,3-trimethylindole (159 mg, 1 mmol) was weighed and dissolved in 30.00 mL of toluene. 4-bromopyrrole-2-carboxaldehyde (172 mg, 1 mmol), piperidine (0.09 mL, 1 mmol), and acetic acid (0.06 mL, 1 mmol) were added in sequence. The mixture was heated and stirred at 90°C for 8 hours until the reaction was complete. The reactant was rotary evaporated and purified by column chromatography to obtain an orange solid I-1 (174.1 mg) with a yield of 37.2%. Weigh compound I-1 (100 mg, 0.21 mmol), take 6 mL of 1,4-dioxane and dissolve it in a mixture, then add 4-diphenylaminophenylboronic acid (60.7 mg, 0.21 mmol), tetrakistriphenylphosphine palladium (2.43 mg, 0.0021 mmol), and potassium hydroxide aqueous solution (potassium hydroxide 23.5 mg, 0.42 mmol, deionized water 210 μL) in sequence. Heat and stir at 60°C for 8 hours until the reaction is complete. Wash the reactant with water, dry it, and purify it by column chromatography to obtain an orange solid I-2 (50.3 mg) with a yield of 37.8%.

[0048] Example 9

[0049] Compound 1 (2,3,3-trimethylindole) (159 mg, 1 mmol) was weighed and dissolved in 30.00 mL of toluene. Piperidine (0.09 mL, 1 mmol) and acetic acid (0.06 mL, 1 mmol) were then added sequentially, followed by the addition of 4-bromopyrrole-2-carboxaldehyde (172 mg, 1 mmol). The mixture was heated and stirred at 90°C for 8 hours until complete. The reaction mixture was rotary evaporated and purified by column chromatography to afford an orange solid (58.5 mg) of I-1 (12.5% ​​yield). When the order of adding piperidine and acetic acid was changed to before adding 4-bromopyrrole-2-carboxaldehyde, as compared to Example 1, the yield decreased by 22.9%. Compound I-1 (100 mg, 0.21 mmol) was weighed and dissolved in 6 mL of 1,4-dioxane. Then, 4-diphenylaminophenylboronic acid (60.7 mg, 0.21 mmol), bis(triphenylphosphine)palladium dichloride (1.47 mg, 0.0021 mmol), and a potassium hydroxide aqueous solution (23.5 mg, 0.42 mmol, 210 μL of deionized water) were added sequentially. The mixture was heated and stirred at 60°C for 8 hours until the reaction was complete. The reactants were washed with water, dried, and purified by column chromatography to obtain an orange solid I-2 (19.3 mg) with a yield of 14.5%. When the catalyst was changed from tetrakistriphenylphosphine palladium to bis(triphenylphosphine)palladium dichloride, the yield decreased by 23.3%.

[0050] Example 10

[0051] Compound 1 (2,3,3-trimethylindole) (159 mg, 1 mmol) was weighed and dissolved in 30.00 mL of DMF. 4-bromopyrrole-2-carboxaldehyde (172 mg, 1 mmol), piperidine (0.09 mL, 1 mmol), and acetic acid (0.06 mL, 1 mmol) were then added sequentially. The mixture was heated and stirred at 90°C for 8 hours until the reaction was complete. The reactants were rotary evaporated and purified by column chromatography to obtain an orange solid (107.2 mg) of I-1 (22.9% yield). When the solvent was changed from toluene to DMF, the yield decreased by 12.5%. Compound I-1 (100 mg, 0.21 mmol) was weighed and dissolved in 6 mL of 1,4-dioxane. 4-Diphenylaminophenylboronic acid (60.7 mg, 0.21 mmol), palladium acetate (0.47 mg, 0.0021 mmol), and a potassium hydroxide aqueous solution (23.5 mg, 0.42 mmol, 210 μL of deionized water) were then added sequentially. The mixture was heated and stirred at 60°C for 8 hours until complete reaction. The reactants were washed with water, dried, and purified by column chromatography to afford an orange solid, I-2 (6.9 mg), in a yield of 5.2%. When the catalyst was changed from tetrakistriphenylphosphine palladium to palladium acetate, the yield decreased by 32.6%.

[0052] Example 11

[0053] Compound 1 2,3,3-trimethylindole (159 mg, 1 mmol) was weighed and dissolved in 30.00 mL of toluene. 4-bromopyrrole-2-carboxaldehyde (172 mg, 1 mmol), piperidine (0.09 mL, 1 mmol), and acetic acid (0.06 mL, 1 mmol) were added in sequence. The mixture was heated and stirred at 90°C for 8 hours until the reaction was complete. The reactant was rotary evaporated and purified by column chromatography to obtain an orange solid I-1 (173.6 mg) with a yield of 37.1%. Weigh compound I-1 (100 mg, 0.21 mmol), take 6 mL of 1,4-dioxane and dissolve it in a mixture, then add 4-cyanophenylboronic acid (27.5 mg, 0.21 mmol), tetrakistriphenylphosphine palladium (2.43 mg, 0.0021 mmol), and potassium hydroxide aqueous solution (potassium hydroxide 23.5 mg, 0.42 mmol, deionized water 210 μL) in sequence. Heat and stir at 60°C for 8 hours until the reaction is complete. Wash the reactant with water, dry it, and purify it by column chromatography to obtain an orange solid I-3 (43.9 mg) with a yield of 33.0%.

[0054] Example 12 Singlet oxygen generation efficiency of compound I-1

[0055] Weigh compound I-1 (4.69 mg, 0.01 mmol) and dissolve it in 1 mL of DCM to prepare a 0.01 mol / L mother solution. Then take 10 μL of the mother solution and dissolve it in 3 mL of DCM to prepare a 0.01 μmol / L test solution. Weigh compound DPBF (2.70 mg, 0.01 mmol) and dissolve it in 1 mL of ethanol to prepare a 0.01 mol / L mother solution. Then take 20 μL of the mother solution and dissolve it in the test solution containing compound I-1. Under 416 nm light source, use DPBF (1,3-diphenylisobenzofuran) to obtain a 0.01 mol / L mother solution. 1 O 2- Singlet oxygen generation efficiency was calculated using a specific trap, using 8-phenyl-1,3,5,7-tetramethyl-2,6-bromo-BODIPY (2Br-BDP) as a reference (ΦΔ = 0.31 in DCM). After laser irradiation, the maximum absorption band of DPBF at 415 nm decreased, and the post-irradiation cell survival rate dropped from 100% to 38%, indicating singlet oxygen generation. The absorbance of DPBF gradually decreased with irradiation time. Based on the degradation of DPBF, the singlet oxygen generation efficiency of I-1 was calculated to be 0.57.

[0056] Example 13 Singlet oxygen generation efficiency of compound I-1

[0057] Weigh compound I-1 (4.69 mg, 0.01 mmol) and dissolve it in 1 mL of DCM to prepare a 0.01 mol / L mother solution. Then take 20 μL of the mother solution and dissolve it in 3 mL of DCM to prepare a 0.02 μmol / L test solution. Weigh compound DPBF (2.70 mg, 0.01 mmol) and dissolve it in 1 mL of ethanol to prepare a 0.01 mol / L mother solution. Then take 20 μL of the mother solution and dissolve it in the test solution containing compound I-1. Under 416 nm light source, use DPBF (1,3-diphenylisobenzofuran) to obtain a 0.01 mol / L mother solution. 1 O 2- Singlet oxygen generation efficiency was calculated using a specific trap, using 8-phenyl-1,3,5,7-tetramethyl-2,6-bromo-BODIPY (2Br-BDP) as a reference (ΦΔ = 0.31 in DCM). After laser irradiation, the maximum absorption band of DPBF at 415 nm decreased, and the cell viability after irradiation dropped from 100% to 25%, indicating singlet oxygen generation. The absorbance of DPBF gradually decreased with irradiation time. Based on the degradation of DPBF, the singlet oxygen generation efficiency of I-1 was calculated to be 0.77.

[0058] Example 14 Singlet oxygen generation efficiency of compound I-1

[0059] Weigh compound I-1 (4.69 mg, 0.01 mmol) and dissolve it in 1 mL DCM to prepare a 0.01 mol / L mother solution. Then take 10 μL of the mother solution and dissolve it in 3 mL DCM to prepare a 0.01 μmol / L test solution. Weigh compound DPBF (2.70 mg, 0.01 mmol) and dissolve it in 1 mL acetonitrile to prepare a 0.01 mol / L mother solution. Then take 20 μL of the mother solution and dissolve it in the test solution containing compound I-1. Under 416 nm light source, use DPBF (1,3-diphenylisobenzofuran) to obtain a 0.01 mol / L mother solution. 1 O 2- Singlet oxygen generation efficiency was calculated using a specific trap, using 8-phenyl-1,3,5,7-tetramethyl-2,6-bromo-BODIPY (2Br-BDP) as a reference (ΦΔ = 0.31 in DCM). After laser irradiation, the maximum absorption band of DPBF at 415 nm decreased, and the cell viability after irradiation dropped from 100% to 46%, indicating singlet oxygen generation. The absorbance of DPBF gradually decreased with irradiation time. Based on the degradation of DPBF, the singlet oxygen generation efficiency of I-1 was calculated to be 0.51.

[0060] Example 15 Singlet oxygen generation efficiency of compound I-1

[0061] Weigh compound I-1 (4.69 mg, 0.01 mmol) and dissolve it in 1 mL of DCM to prepare a 0.01 mol / L mother solution. Then take 10 μL of the mother solution and dissolve it in 3 mL of DCM to prepare a 0.01 μmol / L test solution. Weigh compound DPBF (2.70 mg, 0.01 mmol) and dissolve it in 1 mL of methanol to prepare a 0.01 mol / L mother solution. Then take 20 μL of the mother solution and dissolve it in the test solution containing compound I-1. Under 416 nm light source, the DPBF (1,3-diphenylisobenzofuran) 1 O 2- Singlet oxygen generation efficiency was calculated using a specific trap, using 8-phenyl-1,3,5,7-tetramethyl-2,6-bromo-BODIPY (2Br-BDP) as a reference (ΦΔ = 0.31 in DCM). After laser irradiation, the maximum absorption band of DPBF at 415 nm decreased, and the cell viability after irradiation dropped from 100% to 42%, indicating singlet oxygen generation. The absorbance of DPBF gradually decreased with irradiation time. Based on the degradation of DPBF, the singlet oxygen generation efficiency of I-1 was calculated to be 0.57.

[0062] Example 16 Singlet oxygen generation efficiency of compound I-1

[0063] Weigh compound I-1 (4.69 mg, 0.01 mmol) and dissolve it in 1 mL of DCM to prepare a 0.01 mol / L mother solution. Then take 10 μL of the mother solution and dissolve it in 3 mL of DCM to prepare a 0.01 μmol / L test solution. Weigh compound DPBF (2.70 mg, 0.01 mmol) and dissolve it in 1 mL of ethanol to prepare a 0.01 mol / L mother solution. Then take 20 μL of the mother solution and dissolve it in the test solution containing compound I-1. Under 450 nm light source, use DPBF (1,3-diphenylisobenzofuran) to obtain a 0.01 mol / L mother solution. 1 O 2- Singlet oxygen generation efficiency was calculated using a specific trap, using 8-phenyl-1,3,5,7-tetramethyl-2,6-bromo-BODIPY (2Br-BDP) as a reference (ΦΔ = 0.31 in DCM). After laser irradiation, the maximum absorption band of DPBF at 415 nm decreased, and the cell viability after irradiation dropped from 100% to 58%, indicating singlet oxygen generation. The absorbance of DPBF gradually decreased with irradiation time. Based on the degradation of DPBF, the singlet oxygen generation efficiency of I-1 was calculated to be 0.44.

[0064] Example 17 Singlet oxygen generation efficiency of compound I-2

[0065] Weigh compound I-2 (6.34 mg, 0.01 mmol) and dissolve it in 1 mL DCM to prepare a 0.01 mol / L mother solution. Then take 10 μL of the mother solution and dissolve it in 3 ml DCM to prepare a 0.01 μmol / L test solution. Weigh compound DPBF (2.70 mg, 0.01 mmol) and dissolve it in 1 mL ethanol to prepare a 0.01 mol / L mother solution. Then take 20 μL of the mother solution and dissolve it in the test solution containing compound I-2. Under 412 nm light source, use DPBF (1,3-diphenylisobenzofuran) to obtain a 0.01 mol / L mother solution. 1 O 2- Singlet oxygen generation efficiency was calculated using a specific trap, using 8-phenyl-1,3,5,7-tetramethyl-2,6-bromo-BODIPY (2Br-BDP) as a reference (ΦΔ = 0.31 in DCM). After laser irradiation, the maximum absorption band of DPBF at 415 nm decreased, and the cell viability after irradiation dropped from 100% to 60%, indicating singlet oxygen generation. The absorbance of DPBF gradually decreased with irradiation time. Based on the degradation of DPBF, the singlet oxygen generation efficiency of I-2 was calculated to be 0.43.

[0066] Example 18 Singlet oxygen generation efficiency of compound I-1

[0067] Weigh compound I-3 (4.92 mg, 0.01 mmol) and dissolve it in 1 mL of DCM to prepare a 0.01 mol / L mother solution. Then take 10 μL of the mother solution and dissolve it in 3 mL of DCM to prepare a 0.01 μmol / L test solution. Weigh compound DPBF (2.70 mg, 0.01 mmol) and dissolve it in 1 mL of ethanol to prepare a 0.01 mol / L mother solution. Then take 20 μL of the mother solution and dissolve it in the test solution containing compound I-3. Under 436 nm light source, use DPBF (1,3-diphenylisobenzofuran) to obtain a 0.01 mol / L mother solution. 1 O 2- Singlet oxygen generation efficiency was calculated using a specific trap, using 8-phenyl-1,3,5,7-tetramethyl-2,6-bromo-BODIPY (2Br-BDP) as a reference (ΦΔ = 0.31 in DCM). After laser irradiation, the maximum absorption band of DPBF at 415 nm decreased, and the cell viability after irradiation dropped from 100% to 74%, indicating singlet oxygen generation. The absorbance of DPBF gradually decreased with irradiation time. Based on the degradation of DPBF, the singlet oxygen generation efficiency of I-3 was calculated to be 0.35.

Claims

1. A photosensitizer, characterized in that The chemical structural formula of the photosensitizer is: The substituent R is any one selected from bromine, N,N-dimethylaminophenyl, and p-cyanophenyl.

2. The method for synthesizing a photosensitizer according to claim 1, characterized in that: The method comprises the following synthetic route: Wherein, the substituent R is selected from any one of N,N-dimethylaminophenyl and p-cyanophenyl; (1) Add compound 1 and toluene or DMF to a reaction flask at room temperature, stir to dissolve, then add compound 2, piperidine, and acetic acid, and heat under reflux to obtain a reaction solution; (2) The reaction solution in step (1) was subjected to rotary evaporation, and then separated by silica gel column chromatography to obtain product I-1; (3) adding 1,4-dioxane and compound 3 to compound I-1 in step (2), stirring and dissolving, then adding a catalyst, adjusting the pH with a potassium hydroxide aqueous solution, and heating to obtain a reaction solution; (4) The reaction solution in step (3) is washed with water, extracted, dried, concentrated, and purified to obtain product I, i.e., a photosensitizer.

3. The method according to claim 2, characterized in that In the step (1), the feed ratio of compound 1, compound 2, piperidine and acetic acid is 1:1-10:1-10:1-10.

4. The method according to claim 2, characterized in that The order of adding materials in step (1) is compound 1, toluene or DMF, compound 2, piperidine, and acetic acid.

5. The method according to claim 2, characterized in that The heating reflux reaction temperature in step (1) is 30 to 150° C., and the heating time is 2 to 18 hours.

6. The method according to claim 2, characterized in that The catalyst in step (3) is selected from tetrakistriphenylphosphine palladium, bis(triphenylphosphine)palladium dichloride or palladium acetate.

7. The method according to claim 2, characterized in that In the step (3), the feed ratio of compound I-1 to compound 3 is 1:1-100.

8. The method according to claim 2, characterized in that The heating reaction temperature in step (3) is 30-120° C., and the reaction time is 0.5-24 h.

9. Use of the photosensitizer according to claim 1 in preparing drugs for photodynamic therapy.

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