Aggregation-induced emission type photosensitizer as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of photosensitive materials, and particularly relates to an aggregation-induced emission type photosensitizer as well as a preparation method and application thereof. The aggregation-induced emission type photosensitizer provided by the invention has a structure as shown in any one of formulas I-III. The aggregation-induced emission (AIE) photosensitizer has large Stokes shift, can emit light in a near infrared region I (NIR-I), and is beneficial to penetrating deep biological tissues and reducing light damage to the biological tissues; meanwhile, the AIE type photosensitizer has relatively strong I type active oxygen generation capability, and is expected to be used as a photosensitizer for photodynamic therapy. Formula I, Formula II and Formula III.

Description

Technical Field

[0001] This invention belongs to the field of photosensitive materials technology, specifically relating to an aggregation-induced emission type photosensitizer, its preparation method, and its application. Background Technology

[0002] Cancer is one of the diseases that seriously threaten human health. Traditional treatments such as surgery, chemotherapy and radiotherapy have significant side effects, causing great physical and mental suffering to patients.

[0003] Photodynamic therapy (PDT) is a clinical treatment method that utilizes photosensitizers (PSs) to generate reactive oxygen species (ROS) under appropriate excitation light source irradiation. These ROS oxidize and damage surrounding biomolecules, thereby killing cancer cells or pathogenic microorganisms. PDT offers advantages such as being non-invasive, highly selective, having low drug resistance, and minimal local treatment side effects, thus attracting widespread attention in cancer treatment. Among these, type I free radical ROS, due to their low oxygen concentration dependence, show better therapeutic effects on hypoxic tumors compared to type II ROS (singlet oxygen). Aggregation-induced emission (AIE) photosensitizers exhibit restricted intramolecular motion in an aggregated state, resulting in reduced non-radiative activity and enhanced radiative activity, exhibiting fluorescence enhancement properties. Furthermore, aggregation can increase ROS generation efficiency, providing a new opportunity for PDT's anti-cancer applications. Therefore, the development and design of drugs possessing both AIE properties and strong ROS generation capabilities is of great significance. Summary of the Invention

[0004] In view of this, the purpose of this invention is to provide an aggregation-induced emission (AIE) photosensitizer, its preparation method, and its application. The photosensitizer provided by this invention possesses both AIE properties and a strong ability to generate type I reactive oxygen species.

[0005] This invention provides an aggregation-induced emission photosensitizer having the structure shown in any one of Formulas I to III: Formula I, Formula II, Formula III; In Equations I and II, R1 is or In Equation III, R2 is .

[0006] This invention also provides a method for preparing the aggregation-induced emission photosensitizer described in the above technical solution, comprising the following steps: Under a protective atmosphere, an amino compound having the structure shown in Formula IV or Formula V, hydrochloric acid, and sodium nitrite are mixed and subjected to a diazotization reaction. The resulting reaction system, a cyano compound having the structure shown in Formula VI or Formula VII, an inorganic base, and an organic solvent are mixed and subjected to a Suzuki reaction to obtain an intermediate having the structure shown in Formulas VIII to X. An aggregation-induced emission photosensitizer is obtained by mixing an intermediate having the structure shown in Formulas VIII to X, N,N-diisopropylethylamine, boron trifluoride diethyl ether, and an organic solvent and carrying out a coordination reaction. Formula IV, Formula V, Formula VI, Formula VII Formula VIII, Formula IX Formula X; In Equations IV to X, R1 and R2 are defined as in Equations I to III.

[0007] Preferably, the diazotization reaction is carried out at a temperature of -25 to 0°C for a time of 1 to 24 hours.

[0008] Preferably, the molar ratio of the amino compound, sodium nitrite, cyano compound and inorganic base is 1:(1.1~1.5):(1.1~1.5):(6~10).

[0009] Preferably, the temperature of the Suzuki reaction is 10~30℃ and the time is 8~24h.

[0010] Preferably, the molar ratio of the intermediate, N,N-diisopropylethylamine and boron trifluoride ethyl ether is 1:(5~10):(10~20).

[0011] Preferably, the coordination reaction is carried out at a temperature of 0-25°C for 8-24 hours.

[0012] The present invention also provides the application of the aggregation-induced emission photosensitizer described in the above technical solution or the aggregation-induced emission photosensitizer prepared by the preparation method described in the above technical solution in the preparation of anti-tumor products or tumor diagnostic products.

[0013] Preferably, the tumor includes breast cancer, stomach cancer, esophageal cancer, liver cancer, uterine cancer, or lung cancer.

[0014] Compared with the prior art, the present invention has the following beneficial effects: This invention provides an aggregation-induced emission photosensitizer having the structure shown in any of Formulas I to III. This invention covalently bonds a boron difluoride acceptor with strong electron-withdrawing ability to a triphenylamine (or tetraphenylethylene) donor with strong electron donation, designing and synthesizing a photosensitizer with a molecular weight below 1000 that possesses type I reactive oxygen species generation capability and aggregation-induced emission (AIE) properties.

[0015] The present invention also provides a method for preparing the aggregation-induced emission photosensitizer described in the above technical solution. The preparation method has few steps, is simple to operate, is easy to separate and purify, and is suitable for industrial production. Attached Figure Description

[0016] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0017] Figure 1 The absorption spectrum of 20 μM TPA-BTB in dimethyl sulfoxide solution is shown. Figure 2 The fluorescence spectrum of 20 μM TPA-BTB in dimethyl sulfoxide solution is shown. Figure 3 This is a particle size distribution diagram of TPA-BTB aggregates in aqueous solution; Figure 4 The graph shows the change of the fluorescence intensity ratio of TPA-BTB at 625 nm with the volume fraction of hexane in Hex / DCM mixed solutions with different n-hexane volumes. Figure 5 The mixed solution of TPA-BTB and reactive oxygen species scavenger DCFH under white light irradiation (light power: 100 mW / cm²) 2 The fluorescence spectrum of ( ) changes with illumination time; Figure 6 The mixed solution of TPA-BTB and reactive oxygen species scavenger DCFH under white light irradiation (light power: 100 mW / cm²) 2 The graph shows the change in fluorescence intensity at 530 nm over time. Figure 7 The mixed solution of TPA-BTB and hydroxyl radical (•OH) scavenger APF under white light irradiation (light power: 100mW / cm²) 2 The graph shows the change in the ratio of real-time fluorescence intensity to initial fluorescence intensity at 525 nm over illumination time. Figure 8The mixed solution of TPA-BTB and hydrogen peroxide scavenger DHR 123 under white light irradiation (light power: 100mW / cm²) 2 The graph shows the change in the ratio of real-time fluorescence intensity to initial fluorescence intensity at 525 nm over illumination time. Figure 9 Figure 1 shows the results of dark toxicity and phototoxicity of different concentrations of TPA-BTB on mouse breast cancer cells; Figure 10 Inverted fluorescence microscopy images of live and dead cancer cells stained with commercial live cancer cell probe Calcein-AM and commercial dead cancer cell probe PI during photodynamic killing of mouse breast cancer cells with 10 μMTPA-BTB. Figure 11 The absorption and fluorescence spectra of 20 μM TPA-PYB in dimethyl sulfoxide solution are shown. Detailed Implementation

[0018] This invention provides an aggregation-induced emission photosensitizer having the structure shown in any one of Formulas I to III: Formula I, Formula II, Formula III; In Equations I and II, R1 is or In Equation III, R2 is .

[0019] In this invention, the aggregation-induced emission photosensitizer is preferably any structure of the following formula: , , or .

[0020] This invention also provides a method for preparing the aggregation-induced emission photosensitizer described in the above technical solution, comprising the following steps: Under a protective atmosphere, an amino compound having the structure shown in Formula IV or Formula V, hydrochloric acid, and sodium nitrite are mixed and subjected to a diazotization reaction. The resulting reaction system, a cyano compound having the structure shown in Formula VI or Formula VII, an inorganic base, and an organic solvent are mixed and subjected to a Suzuki reaction to obtain an intermediate having the structure shown in Formulas VIII to X. An aggregation-induced emission photosensitizer is obtained by mixing an intermediate having the structure shown in Formulas VIII to X, N,N-diisopropylethylamine, boron trifluoride diethyl ether, and an organic solvent and carrying out a coordination reaction. Formula IV, Formula V, Formula VI, Formula VII Formula VIII, Formula IX Formula X; In Equations IV to X, R1 and R2 are defined as in Equations I to III.

[0021] Unless otherwise specified, all materials and equipment used in this invention are commercially available products in the field.

[0022] In this invention, under a protective atmosphere, an amino compound having the structure shown in Formula IV or Formula V, hydrochloric acid, and sodium nitrite are mixed and subjected to a diazotization reaction. The resulting reaction system, a cyano compound having the structure shown in Formula VI or Formula VII, an inorganic base, and an organic solvent are mixed and subjected to a Suzuki reaction to obtain an intermediate having the structure shown in Formulas VIII to X.

[0023] The present invention does not have any special requirements for the protective atmosphere; it can be carried out in a conventional protective atmosphere, such as a nitrogen atmosphere or an inert gas atmosphere.

[0024] In this invention, the preferred molar ratio of the amino compound, HCl in hydrochloric acid, and sodium nitrite is (1~1.1):(20~30):1.2.

[0025] In this invention, the temperature of the diazotization reaction is preferably -25~0℃, and the time is preferably 1~24h, specifically 1h.

[0026] In this invention, the inorganic base preferably includes sodium acetate and / or sodium carbonate.

[0027] This invention does not have any special requirements regarding the type of organic solvent; any organic solvent well-known to those skilled in the art can be used, such as ethanol. This invention also does not have any special requirements regarding the amount of organic solvent used, as long as it is sufficient to allow the reaction to proceed smoothly.

[0028] In this invention, the molar ratio of the amino compound, sodium nitrite, cyano compound and inorganic base is preferably 1:(1.1~1.5):(1.1~1.5):(6~10), specifically 1:1.2:1.1:6.

[0029] In this invention, the Suzuki reaction is preferably carried out at room temperature (25°C) with stirring for 8-24 hours, specifically overnight. This invention preferably uses a TLC plate (thin-layer chromatography plate) to monitor the reaction.

[0030] In this invention, the Suzuki reaction preferably further includes: extracting the reaction solution with dichloromethane and water, concentrating the obtained organic phase; performing column chromatography on the concentrate to obtain a purified reaction solution; mixing the purified reaction solution with a mixed solvent of dichloromethane and n-hexane, recrystallizing, and separating the solid and liquid phases to obtain an intermediate; the volume ratio of dichloromethane to water is preferably 1:1; the eluent for the column chromatography includes ethyl acetate and n-hexane, the volume ratio of ethyl acetate to n-hexane is preferably 1:3; and the volume ratio of dichloromethane to n-hexane is preferably 1:10.

[0031] In this invention, the intermediate preferably has a structure shown in any of the following formulas: , , or .

[0032] After obtaining the intermediate having the structure shown in Formulas VIII to X, the present invention mixes the intermediate having the structure shown in Formulas VIII to X, N,N-diisopropylethylamine, boron trifluoride diethyl ether and an organic solvent to carry out a coordination reaction to obtain an aggregation-induced emission type photosensitizer.

[0033] In this invention, the molar ratio of the intermediate, N,N-diisopropylethylamine and boron trifluoride diethyl ether is preferably 1:(5~10):(10~20), and more specifically, it can be 1:7:10.

[0034] In this invention, the organic solvent is preferably dichloromethane.

[0035] The present invention does not have any special requirements for the mixing method; any mixing method known to those skilled in the art can be used.

[0036] In this invention, the temperature of the coordination reaction is preferably 0~25℃, and the time is preferably 8~24h, specifically, it can be stirred overnight at room temperature.

[0037] In this invention, the coordination reaction preferably further includes: post-treatment of the obtained reaction solution, which preferably includes the following steps: concentrating the reaction solution; performing column chromatography on the concentrate to obtain a purified reaction solution; mixing the purified reaction solution with a mixed solvent of dichloromethane and n-hexane, and recrystallizing to separate the solid and liquid phases. This invention does not have special requirements for the concentration method; conventional concentration methods, such as rotary evaporation, are acceptable. The eluent for the column chromatography includes ethyl acetate and n-hexane, with the volume ratio of ethyl acetate to n-hexane preferably being 1:3; and the volume ratio of dichloromethane to n-hexane preferably being 1:10.

[0038] The present invention also provides the application of the aggregation-induced emission photosensitizer described in the above technical solution or the aggregation-induced emission photosensitizer prepared by the preparation method described in the above technical solution in the preparation of anti-tumor products or tumor diagnostic products.

[0039] In this invention, the tumor preferably includes breast cancer, gastric cancer, esophageal cancer, liver cancer, uterine cancer, or lung cancer.

[0040] To further illustrate the present invention, the aggregation-induced emission photosensitizer, its preparation method, and its application provided by the present invention will be described in detail below with reference to the accompanying drawings and embodiments, but these should not be construed as limiting the scope of protection of the present invention.

[0041] Example 1 The chemical reaction formula for preparing the photosensitizer with photodynamic activity in this embodiment is as follows: .

[0042] The specific preparation steps are as follows: Under an inert atmosphere, compound 1 (1 mmol) was added to a 100 mL double-necked round-bottom flask, followed by 10 mL of 2 mol / L dilute hydrochloric acid solution. An aqueous solution of sodium nitrite (1.2 mmol) was added dropwise over half an hour at 0 °C. After the addition was complete, the mixture was stirred for 1 hour. The resulting diazonium salt solution was then added dropwise to an ethanolic solution of compound 2 (1.1 mmol) and sodium acetate (6 mmol). The resulting solution was stirred overnight at room temperature. After the reaction was complete, the reaction solution was concentrated under reduced pressure and subjected to column chromatography using ethyl acetate:n-hexane = 1:3 (v:v) as eluent. Recrystallization was performed using a mixed solvent of dichloromethane:n-hexane = 1:10 (v:v) to give an orange-red solid 3 in 63% yield.

[0043] Compound 3 (0.448 mmol) was added to a 100 mL double-necked round-bottom flask, followed by a solution of N,N-diisopropylethylamine (DIPEA) (3.142 mmol) in DCM (dichloromethane), and finally boron trifluoride diethyl ether (4.48 mol). The resulting solution was stirred overnight at room temperature. After the reaction was complete, the reaction solution was concentrated under reduced pressure and subjected to column chromatography with ethyl acetate:n-hexane = 1:3 (v:v) as the eluent. Recrystallization was performed with a mixed solvent of dichloromethane:n-hexane = 1:10 (v:v) to give a red solid II-b (denoted as TPA-BTB) in 56% yield.

[0044] The red solid product obtained in this embodiment was characterized, and the specific NMR data are as follows: TPA-BTB (red solid): 1 H NMR (600 MHz, CDCl3) δ 8.29 (d,J = 8.3 Hz, 2H), 7.97 (d, J = 8.1 Hz, 2H), 7.74 (d, J = 8.9 Hz, 2H), 7.64 (t, J = 7.6 Hz, 2H), 7.15–7.08 (m, 10H). 13 C NMR (151 MHz, CDCl3), δ 157.46, 147.71, 147.17, 142.69,138.76, 129.44, 129.14, 128.76, 127.79, 125.01, 123.67, 122.75, 122.60,122.07, 119.80, 114.98, 103.96. HRMS: [M+Na] + calcd: 516.1237; found 516.1240. Based on the characterization data above, it can be seen that the obtained aggregation-induced emission photosensitizer TPA-BTB with the ability to generate type I reactive oxygen species is a compound with the structure shown in formula II-b.

[0045] Performance testing: (1) Photoluminescence ability test of photosensitizer: 20 μL of TPA-BTB (Ⅱ-b) dimethyl sulfoxide solution (2 mM) was added to 2 mL of dimethyl sulfoxide to obtain 20 μM TPA-BTB solution, and the absorption spectrum and fluorescence spectrum of the mixed solution were measured.

[0046] Figure 1 The absorption spectrum of 20 μM TPA-BTB in dimethyl sulfoxide solution; Figure 2 The fluorescence spectrum of 20 μM TPA-BTB in dimethyl sulfoxide solution is given by... Figure 1 and Figure 2 It can be seen that under irradiation with 400 nm excitation light, TPA-BTB emits fluorescence at 490 nm and has a Stokes shift of 90 nm, indicating that TPA-BTB has good luminescence ability.

[0047] (2) Photosensitizer aggregate particle size test: 20 μL TPA-BTB DMSO solution (2 mM) was added to 2 mL PBS solution (5 mM, pH 7.4) to obtain 20 μM TPA-BTB solution, and the particle size distribution of aggregates in the mixed solution was determined.

[0048] Figure 3 This is a particle size distribution diagram of TPA-BTB aggregates in aqueous solution. Figure 3 It can be seen that the particle size distribution of TPA-BTB aggregates in aqueous solution is concentrated at around 84 nm, which is a moderate particle size, indicating that TPA-BTB aggregates can effectively bind to cancer cells.

[0049] (3) AIE property test of TPA-BTB: TPA-BTB DMSO solution (1 mM) was added to Hex / DCM mixed solutions with different n-hexane volume fractions to obtain TPA-BTB solution with a concentration of 10 μM. The ratio of real-time fluorescence intensity to initial fluorescence intensity in mixed solutions with different n-hexane volume fractions was measured at 625 nm with 550 nm as the excitation wavelength.

[0050] Figure 4 The fluorescence intensity ratio of TPA-BTB at 625 nm in Hex / DCM mixed solutions with different n-hexane volume fractions varies with the n-hexane volume fraction. The n-hexane volume fractions corresponding to low to high values ​​are 0%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, and 99%, respectively, with an excitation wavelength of 500 nm. Figure 4 As can be seen, the fluorescence emission intensity ratio of TPA-BTB gradually increases with the increase of the n-hexane volume fraction, reaching its strongest value at 90%, indicating that TPA-BTB has AIE properties.

[0051] (4) Test of reactive oxygen species generation capacity of photosensitizer: 20 μL of TPA-BTB dimethyl sulfoxide solution (2 mM) was added to 2 mL of PBS solution (pH 7.4, 5 mM). The reactive oxygen species scavenger 2',7'-dichlorodihydrofluorescein (DCFH) was added to the above solution. Using 489 nm as the excitation light source, the fluorescence spectrum of the mixed solution at 500~600 nm was measured. Then, the mixed solution was irradiated with a solar simulator, and the fluorescence spectrum of the mixed solution at 500~600 nm was measured as a function of irradiation time.

[0052] Figure 5 The fluorescence spectrum of the mixed solution changes with illumination time (0~10 min, tested once per minute). Figure 6 The fluorescence intensity at 530 nm changes with illumination time. From... Figure 5 and Figure 6 It can be seen that as the illumination time increases, the fluorescence intensity of the reactive oxygen species scavenger DCFH gradually increases and eventually reaches a plateau and remains stable, indicating that TPA-BTB has the ability to generate reactive oxygen species and is a potential photodynamic anticancer photosensitizer.

[0053] (5) The specific steps for testing the hydroxyl radical (•OH) generation capacity of TPA-BTB are as follows: Aminophenyl fluorescein (APF) was used as an indicator to detect •OH in the solution. When hydroxyl radicals are generated in the system, APF will be oxidized and emit strong fluorescence at 515 nm. 10 µM TPA-BTB was dissolved in 2 mL of PBS solution containing 1 μL of APF (concentration: 5 mM). The mixture was then placed in a cuvette and tested using a solar simulator (0.1 W / cm²). 2 Irradiation was performed. Fluorescence changes at 525 nm were recorded using a fluorescence spectrophotometer (excitation wavelength: 490 nm).

[0054] Figure 7 The fluorescence value of TPA-BTB in a mixed solution with the hydroxyl radical scavenger APF in water changes with illumination time. When the solution is exposed to solar simulator irradiation in the presence of these two nanoparticles, the fluorescence signal of the APF probe increases significantly, indicating that the nanoparticles have the ability to generate hydroxyl radicals.

[0055] (6) The hydrogen peroxide (H2O2) generation capacity test of TPA-BTB is as follows: Dihydrorhodamine 123 (DHR 123) was used as an indicator to detect H2O2 in solution. When H2O2 is generated in the system, DHR 123 will be oxidized and emit strong fluorescence at 525 nm. 10 µM TPA-BTB was dissolved in 2 mL of PBS solution containing 5 μL of DHR 123 (concentration: 1 mM). The mixture was then placed in a cuvette and tested using a solar simulator (0.1 W / cm²). 2 Irradiation was performed. Fluorescence changes at 525 nm were recorded using a fluorescence spectrophotometer (excitation wavelength: 480 nm).

[0056] Figure 8 The fluorescence value of TPA-BTB in a mixed solution with hydrogen peroxide scavenger DHR 123 in water changes with illumination time. When the solution was exposed to solar simulator irradiation in the presence of these two nanoparticles, the fluorescence signal of the DHR 123 probe increased significantly, indicating that the nanoparticles have the ability to generate hydrogen peroxide.

[0057] (7) The cytotoxicity test of TPA-BTB is performed as follows: Logarithmic growth phase 4T1 cells were evenly seeded into 96-well plates (approximately 5000 cells / well) and pre-cultured at 37 ℃ in a 5% CO2 incubator for 24 h. Subsequently, the culture medium in the 96-well plates was replaced with fresh medium containing different concentrations of TPA-BTB, and the plates were incubated for another 20 h. Then, they were placed under solar simulator irradiation (0.1... Cells were incubated for 30 min, with a dark control group (cells not exposed to light) reserved. After incubation for another 4 h, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetraazolium bromide (MTT solution, 10 μL, 5 mg / mL) was added and cultured for another 4 h. Then, the medium containing MTT was removed, and 100 μL of DMSO was added to each well to dissolve the formazan. Finally, the absorbance at 490 nm was measured using a microplate reader. Cells incubated with only the medium served as a control. The results are expressed as the percentage of viable cells after TPA-BTB treatment relative to the control group. Relative cell viability was calculated using the following formula: Cell viability (%) = (OD) sample -OD background ) / (OD control -OD background )×100% (Formula 1).

[0058] Figure 9 The effects of different concentrations of TPA-BTB on the dark toxicity and phototoxicity of 4T1 cells were investigated. Figure 9 It can be seen that even under light-free conditions, with a TPA-BTB concentration as high as 10 μM, the survival rate of 4T1 cells remained above 80%, indicating that TPA-BTB has good biocompatibility and negligible toxicity under dark conditions. However, after 30 minutes of irradiation using a solar simulator, TPA-BTB exhibited significant concentration-dependent cytotoxicity; at a concentration of 6 μM, the survival rate of 4T1 cells dropped to below 30%, demonstrating a highly efficient photoactivated killing ability against tumor cells.

[0059] Logarithmic growth phase 4T1 cells were evenly seeded into 96-well plates (approximately 5000 cells / well) and pre-cultured at 37 ℃ in a 5% CO2 incubator for 24 h. Subsequently, the culture medium in the 96-well plates was replaced with fresh medium containing different concentrations of TPA-BTB, and the plates were incubated for another 20 h. 1 mL of the cultured mouse breast cancer cells was washed twice with PBS solution (5 mM, pH 7.4) (1 mL each time), and then diluted with PBS to a concentration of 2 × 10⁻⁶. 7CFU / mL was added to 5 μL of DMSO solution (2 mM) containing TPA-BTB. The cell suspension was incubated in a shaker at 37℃ and 220 r / min for 30 min, and then irradiated with a solar simulator equipped with a 400 nm filter for 40 min. Different commercial probes were added, and the cells were observed and photographed under an inverted fluorescence microscope, serving as the experimental group. The control group followed the same method, except that TPA-BTB was not added; observation and photography were then performed.

[0060] Figure 10 Inverted fluorescence microscopy images of live and dead cancer cells obtained by photodynamic killing of mouse thymoma cells with 10 μM TPA-BTB stained with commercial live cancer cell probe Calcein-AM (green fluorescence) and commercial dead cancer cell probe PI (red fluorescence). Figure 10 As can be seen, in the phototoxicity images of the experimental group, there was almost no fluorescence signal from the commercially available live cancer cell probe Calcein-AM, while all the fluorescence signals were from the commercially available dead cancer cell probe PI. This means that the cancer cells were all in a dead state at this time, indicating that TPA-BTB photodynamic therapy can effectively kill mouse thymoma cells. Figure 9 The results were consistent.

[0061] Example 2 The only difference from Example 1 is that compound 2 is replaced with .

[0062] The orange solid product obtained in this embodiment was characterized, and the specific NMR data are as follows: TPA-PYB (orange solid, 36% yield): ¹H NMR (600 MHz, CDCl₃) δ 8.67 (d, J = 5.7 Hz, 2H), 8.25 (d, J = 7.5 Hz, 2H), 7.93 (d, J = 8.4 Hz, 2H), 7.62 (d, J = 8.7 Hz, 2H), 7.17 – 7.12 (m, 10H). ¹³C NMR (151 MHz, CDCl₃) δ 147.44, 146.60, 142.61, 141.46, 139.95, 139.32, 129.41, 129.33, 124.93, 124.58, 123.58,123.22, 123.12, 121.47, 121.45, 121.43, 120.52, 115.47, 14.10. HRMS: [M + Na] 154calcd: 460.1516; found 460.1526. The obtained photosensitizer has the following structural formula: .

[0063] Performance testing: Photoluminescence ability test of photosensitizer: 20 μL of TPA-PYB(Ⅱ-b) dimethyl sulfoxide solution (2 mM) was added to 2 mL of dimethyl sulfoxide to obtain a 20 μM TPA-PYB solution, and the absorption spectrum and fluorescence spectrum of the mixed solution were measured.

[0064] Figure 11 The left-middle image shows the absorption spectrum of 20 μM TPA-PYB in dimethyl sulfoxide solution, and the right-middle image shows the fluorescence spectrum of 20 μM TPA-PYB in dimethyl sulfoxide solution. Figure 11 It can be seen that under irradiation with 400 nm excitation light, TPA-PYB emits fluorescence at 715 nm and has a Stokes shift of 95 nm, indicating that TPA-PYB has good luminescence ability.

[0065] Example 3 The only difference from Example 1 is that compound 1 is replaced with .

[0066] The orange-yellow solid product obtained in this embodiment was characterized, and the specific NMR data are as follows: TPE-BTB (orange-yellow solid, 63% yield): ¹H NMR (600 MHz, CDCl₃) δ 8.03 (d, J = 8.2 Hz, 2H), 7.99 (d, J = 8.0 Hz, 2H), 7.59 (t, J = 7.2 Hz, 2H), 7.52 (t, J = 7.6 Hz, 2H), 7.22 (d, J = 8.6 Hz, 4H), 7.16 (t, J = 7.2 Hz, 14H). ¹³C NMR (151 MHz, CDCl₃) δ 157.55, 143.57, 143.52, 143.44, 143.37, 142.68, 141.88, 139.96, 132.13, 131.42, 131.32, 129.25, 128.86, 127.98, 127.90, 127.78,127.65, 126.81, 126.63, 126.56, 122.63, 120.29, 120.27, 120.00, 119.98,119.96, 114.70. HRMS: [M+H]+ calcd: 581.1778; found 581.1760. The obtained photosensitizer has the following structural formula: .

[0067] Example 4 The only difference from Example 1 is that compound 1 is replaced with The amount of compound 2 was adjusted to twice the number of mol in Example 1.

[0068] The orange-red solid product obtained in this embodiment was characterized, and the specific NMR data are as follows: TPE-2BTB (orange-red solid, 54% yield): ¹H NMR (600 MHz, CDCl₃) δ 8.30 (d, J = 8.3 Hz, 4H), 7.97 (d, J = 8.3 Hz, 4H), 7.75 – 7.70 (m, 4H), 7.66 – 7.61 (m, 4H), 7.10 (td, J = 18.1, 16.8, 5.7 Hz, 10H). ¹³C NMR (151 MHz, CDCl₃) δ 162.52, 157.54, 143.24, 143.17, 142.94, 142.68, 140.82, 132.73, 132.16, 131.61, 131.43, 129.25, 128.86, 128.49, 128.05, 128.01, 127.97, 127.80,127.04, 126.79, 122.64, 122.61, 120.46, 120.26, 120.00, 115.29, 114.69,104.48, 67.97, 36.45, 31.44. HRMS: [M+Na]+ calcd: 815.1737; found 851.1743. The obtained photosensitizer has the following structural formula: .

[0069] As can be seen from the above embodiments, the aggregation-induced emission photosensitizer with type I reactive oxygen species provided by the present invention has a simple synthesis step, simple separation and purification operation, a large Stokes shift, easily generates near-infrared fluorescence, and has excellent ability to generate type I reactive oxygen species.

[0070] Although the above embodiments have provided a detailed description of the present invention, they are only some embodiments of the present invention, not all embodiments. People can obtain other embodiments based on the present invention without creative effort, and these embodiments all fall within the protection scope of the present invention.

Claims

1. An aggregation-induced emission photosensitizer, characterized in that, It has the structure shown in any of Equations I to III: Formula I, Formula II, Formula III; In Equations I and II, R1 is or In Equation III, R2 is .

2. The method for preparing the aggregation-induced emission photosensitizer according to claim 1, characterized in that, Includes the following steps: Under a protective atmosphere, an amino compound having the structure shown in Formula IV or Formula V, hydrochloric acid, and sodium nitrite are mixed and subjected to a diazotization reaction. The resulting reaction system, a cyano compound having the structure shown in Formula VI or Formula VII, an inorganic base, and an organic solvent are mixed and subjected to a Suzuki reaction to obtain an intermediate having the structure shown in Formulas VIII to X. An aggregation-induced emission photosensitizer is obtained by mixing an intermediate having the structure shown in Formulas VIII to X, N,N-diisopropylethylamine, boron trifluoride diethyl ether, and an organic solvent and carrying out a coordination reaction. Formula IV, Formula V, Formula VI, Formula VII Formula VIII, Formula IX Formula X; In Equations IV to X, R1 and R2 are defined as in Equations I to III.

3. The preparation method according to claim 2, characterized in that, The diazotization reaction is carried out at a temperature of -25 to 0°C for a time of 1 to 24 hours.

4. The preparation method according to claim 2, characterized in that, The inorganic base includes sodium acetate and / or sodium carbonate.

5. The preparation method according to claim 2 or 4, characterized in that, The molar ratio of the amino compound, sodium nitrite, cyano compound and inorganic base is 1:(1.1~1.5):(1.1~1.5):(6~10).

6. The preparation method according to claim 2, characterized in that, The Suzuki reaction was carried out at a temperature of 10-30°C for 8-24 hours.

7. The preparation method according to claim 2 or 6, characterized in that, The molar ratio of the intermediate, N,N-diisopropylethylamine, and boron trifluoride ethyl ether is 1:(5~10):(10~20).

8. The preparation method according to claim 2, characterized in that, The coordination reaction is carried out at a temperature of 0~25℃ for 8~24h.

9. The use of the aggregation-induced emission photosensitizer according to claim 1 or the aggregation-induced emission photosensitizer prepared by any one of claims 2 to 8 in the preparation of antitumor products or tumor diagnostic products.

10. The application according to claim 9, characterized in that, The tumors include breast cancer, stomach cancer, esophageal cancer, liver cancer, uterine cancer, or lung cancer.

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