Novel selenium-rhodamine photosensitizer and synthesis method thereof

Abstract

The invention aims to provide a novel selenium-rhodamine photosensitizer and a synthesis method thereof, and belongs to the technical field of fluorescent dyes, the method has the advantages of simple route, cheap and easily available raw materials, simple product purification, and easy quantitative preparation and further functionalization of the selenium-rhodamine photosensitizer. The synthesized photosensitizer has the properties of good water solubility, light stability, high singlet oxygen yield and the like, and has important value in development and application of photodynamic therapy reagents.

Description

Technical Field

[0001] The invention belongs to the technical field of fluorescent dyes, and in particular relates to a novel selenium-rhodamine photosensitizer and a synthesis method thereof. Background Art

[0002] As a common malignant disease, cancer has become the biggest threat to human health and safety worldwide. Photodynamic therapy (PDT) is a treatment method that relies on photosensitizers (PS) to produce highly cytotoxic reactive oxygen species (ROS) under light irradiation conditions to kill cancer cells. Photosensitizers, light of a specific wavelength, and oxygen are the three elements of photodynamic therapy. When light is excited, PS is excited from the ground state (S0) to the singlet state (S1), and then to the excited triplet state (T1) through intersystem crossing (ISC). The photosensitizer in the excited triplet state reacts with oxygen molecules in the environment and converts them into superoxide anion radicals (O2 - •) or singlet oxygen ( 1 O2), the process of producing superoxide free radicals is usually called type I photodynamic process, and the process of producing singlet oxygen is called type II photodynamic process. Singlet oxygen or superoxide anion free radicals produced under light have significant biological toxicity, which can damage cells and biological tissues by oxidizing biological molecules such as proteins, nucleic acids, and liposomes in cells, and ultimately lead to apoptosis or necrosis of cancer cells. Photosensitizers are the key basic materials for photodynamic therapy technology. Most commercial photosensitizers are derived from fluorescent dyes, and their photophysical properties, such as absorption and emission wavelengths, molar absorption coefficients, solubility, singlet oxygen yield, etc., will have an important impact on the effect of photodynamic therapy.

[0003] In recent years, through the chemical modification of the structure of rhodamine dyes, many fluorescent dyes with excellent properties have been developed, which has substantially promoted the progress of fluorescence technology in the field of biomedical imaging. For example, through the single-atom modification of the 10-position oxygen atom, a series of rhodamine derivatives, such as carbon-rhodamine, selenium-rhodamine, silicon-rhodamine, germanium-rhodamine, and phosphorus-rhodamine, have been reported one after another. These rhodamine derivatives have different properties and are widely used in the development and application of fluorescent probes, super-resolution fluorescence imaging, and photodynamic therapy agents. Among them, compared with carbon-rhodamine, silicon-rhodamine and phosphorus-rhodamine dyes, selenium-rhodamine dyes significantly improve the intersystem crossing efficiency due to their inherent heavy atom effect, resulting in high singlet oxygen efficiency. In addition, selenium-rhodamine dyes also have longer excitation and emission wavelengths (>600 nm), good photostability and water solubility, so they have important application prospects in photodynamic therapy. However, the synthesis of traditional selenium-rhodamine dyes is complicated (US 2006 / 0040908 A1, CN 115010698 A), the overall synthesis rate is low, and it is limited to some specific dye structures, which to some extent limits its application in the field of photodynamic therapy. Therefore, it is particularly important to develop a new method for efficiently preparing selenium-rhodamine photosensitizers. Summary of the invention

[0004] The purpose of the present invention is to provide a novel selenium-rhodamine photosensitizer and a synthesis method thereof, which has a simple route, cheap and readily available raw materials, simple product purification, and is easy to quantitatively prepare and further functionalize the selenium-rhodamine photosensitizer. The synthesized photosensitizer has properties such as good water solubility, photostability, and high singlet oxygen yield, and has important value in the development and application of photodynamic therapy agents.

[0005] The present invention adopts the following technical solution: A novel selenium-rhodamine photosensitizer, the general structural formula of which is as follows: ; wherein R1 and R2 are each independently selected from any one of H, C1-10 straight-chain alkyl, branched alkyl, and benzyl; or R1 forms a 6-membered nitrogen-containing heterocyclic ring with the N, C1 and C3 to which it is connected or with the N, C4 and C5 to which it is connected, and / or R2 forms a 6-membered nitrogen-containing heterocyclic ring with the N, C1 and C2 to which it is connected or with the N, C5 and C6 to which it is connected; X - Including F - , Cl - Br - ,I - 、ClO4 - 、CH3COO - CF3COO - Any one of .

[0006] A method for synthesizing a novel selenium-rhodamine photosensitizer comprises the following steps: Step 1, Synthesis of Intermediate 1 3-iodoaniline and potassium carbonate were dissolved in anhydrous acetonitrile, and a halogenated hydrocarbon was added thereto at room temperature, and then the mixture was heated to 85°C and refluxed for reaction for 12 hours. After the reaction was completed, the mixture was cooled and filtered to remove the remaining potassium carbonate. The filtrate was diluted with water and extracted with dichloromethane, and the organic phase was collected and dried over anhydrous sodium sulfate. After the solvent was spin-dried, the crude product was separated by column chromatography to obtain a colorless oily intermediate compound 1; Step 2: Synthesis of Intermediate 2 The intermediate 1 was dissolved in dry dimethyl sulfoxide, potassium phosphate, selenium powder and a catalytic amount of cuprous iodide were added thereto, and the mixture was heated to 110°C under nitrogen protection for 12 hours. After the reaction was completed and cooled to room temperature, an appropriate amount of water was added to the reaction system, and the reaction system was filtered to remove the potassium phosphate and selenium powder remaining in the reaction, and then extracted with dichloromethane three times. The collected organic phase was dried over anhydrous sodium sulfate, filtered, and then dried under reduced pressure. The crude product was separated by column chromatography to obtain an orange-red oily liquid 2; Step 3: Synthesis of Intermediate 3 The intermediate 2 was dissolved in dry dimethyl sulfoxide, and the intermediate 1, potassium carbonate, reduced iron powder and a catalytic amount of copper sulfide were added thereto. The mixture was heated to 100°C under nitrogen protection for 6 hours. After the reaction was completed, the mixture was cooled to room temperature, and the reaction solution was diluted with an appropriate amount of dichloromethane. The reaction solution was filtered under reduced pressure through diatomaceous earth to remove the potassium carbonate, reduced iron powder and copper sulfide remaining in the reaction. Then, 3 times the volume of water was added to the filtrate, and the mixture was extracted with dichloromethane. The collected organic phase was dried over anhydrous sodium sulfate, filtered, and then dried under reduced pressure. The crude product was separated by column chromatography to obtain a light yellow solid compound 3. Step 4: Synthesis of Intermediate 4 Under ice bath conditions, the intermediate 3 was dissolved in dry N, N-dimethylformamide, and a DMF solution containing N-bromosuccinimide was added through a dropping funnel within 10 minutes, and then reacted at room temperature for 6 hours. An appropriate amount of distilled water was added to the system to quench the reaction, and then diluted with brine, followed by extraction with ethyl acetate three times. The collected organic phase was dried over anhydrous sodium sulfate, filtered, and then dried under reduced pressure. The crude product was separated by column chromatography to obtain a white solid compound 4; Step 5: Synthesis of Selenium-Rhodamine Photosensitizer Under nitrogen protection, the intermediate 4 is dissolved in tetrahydrofuran, cooled to -78°C in a liquid nitrogen acetone bath, and then tert-butyl lithium tetrahydrofuran solution is added dropwise within 10 minutes, the reaction is maintained at -78°C and stirred for 1 hour, and then methyl isonicotinate or its derivative is added dropwise, reacted at -78°C for 30 minutes and then warmed to room temperature, stirred overnight, quenched with 2 mol / L dilute hydrochloric acid aqueous solution, and then stirred at room temperature for 30 minutes, and diluted with saturated ammonium chloride aqueous solution, and then extracted with dichloromethane, and the collected organic phase is dried over anhydrous sodium sulfate, filtered, and then decompressed and dried. The crude product is separated by neutral alumina column chromatography, and further crystallized with a mixed solvent of ether and ethanol to obtain a pure selenium-rhodamine photosensitizer.

[0007] Furthermore, the halogenated hydrocarbon in the first step includes bromoalkane or iodoalkane; and the molar ratio of the 3-iodoaniline, halogenated hydrocarbon and potassium carbonate is 1:2.2:2.2.

[0008] Furthermore, in the second step, the molar ratio of the intermediate 1, potassium phosphate, selenium powder and cuprous iodide is 1:3:3:0.1.

[0009] Furthermore, in the third step, the molar ratio of the intermediate 1, the intermediate 2, potassium carbonate, the reduced iron powder and the copper sulfide is 1:1:2:1.2:0.1.

[0010] Furthermore, in the fourth step, the molar ratio of the intermediate 3 to N-bromosuccinimide is 1:2.2.

[0011] Furthermore, in the fifth step, the molar ratio of the intermediate 4, tert-butyl lithium, methyl isonicotinate or its derivative is 1:4:2.

[0012] The beneficial effects of the present invention are as follows: The method adopted by the present invention has the advantages of simple route, high yield and easy separation and purification. The prepared selenium-rhodamine photosensitizer has a large molar extinction coefficient (ε max =0.99×10 5 M -1 cm -1 ), high singlet oxygen yield ( Φ Δ = 90.6%), good water solubility (SeR1 in the concentration range of 0-40 μM shows a good linear relationship with its absorbance at 590 nm), etc., and is of great value in the development and application of photodynamic therapy agents. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Figure 1 For intermediate 1 1 HNMR spectrum; Figure 2 is the HRMS spectrum of intermediate 1; Figure 3 For intermediate 2 1 HNMR spectrum; Figure 4 is the HRMS spectrum of intermediate 2; Figure 5 For intermediate 3 1 HNMR spectrum; Figure 6 is the HRMS spectrum of intermediate 3; Figure 7 For intermediate 4 1 HNMR spectrum; Figure 8 is the HRMS spectrum of intermediate 4; Fig. 9 Selenium-rhodamine photosensitizer SeR1 1 HNMR spectrum; Fig.10 is the HRMS spectrum of selenium-rhodamine photosensitizer SeR1; Fig.11 Selenium-rhodamine photosensitizer SeR2 1 HNMR spectrum; Fig.12 is the HRMS spectrum of selenium-rhodamine photosensitizer SeR2; Fig.13 is the normalized UV-visible absorption spectrum of selenium-rhodamine photosensitizer SeR1 in dichloromethane (DCM), acetonitrile (MeCN), methanol (MeOH), and PBS buffer solution; Fig.14 is the normalized fluorescence emission spectrum of selenium-rhodamine photosensitizer SeR1 in dichloromethane (DCM), acetonitrile (MeCN), methanol (MeOH), and PBS buffer solution; Fig.15 The figure shows the change of the UV-visible absorption spectrum of the singlet oxygen indicator 9,10-anthracenebis(methylene)-dimalonic acid (ABDA) in PBS under light conditions caused by the selenium-rhodamine photosensitizer SeR1 as a function of light exposure time; Fig.16 This is a graph showing the change in absorbance at 380 nm of ABDA induced by selenium-rhodamine photosensitizer SeR1 and commercial dye Rose Bengal under light conditions over time; Fig.17 , 18 is the concentration-dependent absorption spectrum change of SeR1 and the corresponding intensity change at 590 nm; Fig.19 is a synthetic method route map of the present invention; Fig. 20This is a flow chart of the synthesis method of the selenium-rhodamine photosensitizer SeR1 in Example 1; Fig.21 This is a flow chart of the synthesis method of selenium-rhodamine photosensitizer SeR2 in Example 2. DETAILED DESCRIPTION

[0014] In order to make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all the embodiments; based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0015] Example 1 Synthesis method of selenium-rhodamine photosensitizer SeR1 (1) Synthesis of intermediate 1 Under nitrogen protection, 3-iodoaniline (5.00 g, 22.85 mmol) and potassium carbonate (6.95 g, 50.27 mmol) were dissolved in dry acetonitrile, iodomethane (7.14 g, 50.27 mmol) was added thereto at room temperature, and then the mixture was heated to 85 °C and refluxed for 12 hours. After the reaction was completed, the temperature was lowered, and the potassium carbonate remaining in the reaction was removed by suction filtration. The filtrate was diluted with water and then extracted with dichloromethane. The organic phase was collected and dried over anhydrous sodium sulfate and spin-dried. The crude product was separated by silica gel column chromatography (eluent: petroleum ether) to obtain colorless oily intermediate 1 (4.4 g, yield 78%). 1 H NMR (600 MHz, CDCl3) δ(ppm): 7.07 (d, J =7.2 Hz, 2H), 6.97 (t, J 1 =8.0 Hz, J 2 =8.0 Hz, 1H), 6.70 (m, 1H),2.96 (s, 6H).ESI-MS: [M+H] + Calcd for 247.993, Found 247.993.

[0016] (2) Synthesis of intermediate 2 The intermediate 1 (2.47 g, 10 mmol) was dissolved in 25 mL of dry DMSO, potassium phosphate (6.37 g, 30 mmol), selenium powder (2.37 g, 30 mmol) and a catalytic amount of cuprous iodide (0.19 g, 1 mmol) were added thereto, and the mixture was heated to 110 °C under nitrogen protection for 12 hours. After the reaction was completed and cooled to room temperature, an appropriate amount of water was added to the reaction system, and the potassium phosphate and selenium powder remaining in the reaction were removed by vacuum filtration, and then extracted three times with dichloromethane. The collected organic phase was dried over anhydrous sodium sulfate, filtered, and then vacuum-dried. The crude product was separated by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 20 / 1, v / v) to obtain an orange-red oily intermediate 2 (3.15 g, yield 80%). 1 H-NMR (600 MHz, CDCl3) δ(ppm): δ 7.13 (t, J1= 7.8 Hz, J2=8.4 Hz, 2H), δ 7.01 (d, J=8.4 Hz, 4H), 6.62(d, J = 7.8 Hz, 2H), δ 2.93 (s, 12H). ESI-MS: [M+H] + calcd for 401.003, Found401.003.

[0017] (3) Synthesis of intermediate 3 Intermediate 2 (4.01 g, 10 mmol) was dissolved in 40 mL of dry DMSO, and intermediate 1 (2.47 g, 10 mmol), potassium carbonate (4.15 g, 30 mmol), reduced iron powder (0.67 g, 12 mmol) and catalytic amount of copper sulfide (0.095 g, 1 mmol) were added thereto. The mixture was heated to 100 °C under nitrogen protection for 6 hours and cooled to room temperature after the reaction. The reaction solution was diluted with an appropriate amount of dichloromethane and filtered under reduced pressure through diatomaceous earth to remove the remaining potassium carbonate, reduced iron powder and copper sulfide. Then, 3 times the volume of water was added to the filtrate, and the mixture was extracted with dichloromethane. The collected organic phase was dried over anhydrous sodium sulfate, filtered, and then dried under reduced pressure. The crude product was separated by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 10 / 1, v / v) to obtain a light yellow solid intermediate 3 (2.8 g, yield 87%). 1H-NMR (600 MHz, CDCl3) δ (ppm): δ7.18 - 7.12 (m, 2H), 6.91 (d, J = 3.5 Hz, 2H), 6.84 (t, J = 7.1 Hz, 2H), 6.65(d, J = 5.3 Hz, 2H), 2.92 (d, J = 4.9 Hz, 12H).ESI-MS: [M+H] + calcd for321.086, Found 321.086.

[0018] (4) Synthesis of intermediate 4 The intermediate 3 (2.00 g, 6.23 mmol) was dissolved in 10 mL of dry DMF, and 10 mL of DMF solution containing N-bromosuccinimide (2.44 g, 13.71 mmol) was added dropwise through a dropping funnel under an ice bath within 10 minutes, and then reacted at room temperature for 6 hours. An appropriate amount of distilled water was added to the system to quench the reaction, and then diluted with brine, followed by extraction with ethyl acetate three times. The collected organic phase was dried over anhydrous sodium sulfate, filtered, and then dried under reduced pressure. The crude product was separated by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 60:1, v / v) to obtain a white solid intermediate 4 (2.25 g, yield 75%) 1 H-NMR (600 MHz, CDCl3) δ (ppm): δ 7.40 (d, J = 8.8 Hz, 2H), 6.66 (d, J = 3.0Hz, 2H), 6.51 (dd, J 1 = 3.0, J 2 = 8.8 Hz, 2H), 2.82 (s, 12H).ESI-MS: [M+H] + calcdfor 478.906, Found 478.905.

[0019] (5) Synthesis of Selenium-Rhodamine Photosensitizer SeR1 Under nitrogen protection, intermediate 4 (239 mg, 0.51 mmol) was dissolved in dry tetrahydrofuran (10 mL), cooled to -78 °C in a liquid nitrogen acetone bath, and then 1.3 mol / L tert-butyl lithium tetrahydrofuran solution (1.69 mL, 2.20 mmol) was slowly added dropwise, and the reaction was stirred at -78 °C for 1 hour. Then methyl isonicotinate (151 mg, 1.11 mmol) was added dropwise, reacted at -78 °C for 30 minutes, and then warmed to room temperature and stirred overnight. The reaction was then quenched with 10 mL of 2 mol / L dilute hydrochloric acid aqueous solution, and then stirred at room temperature for 30 minutes. Saturated ammonium chloride aqueous solution was added for dilution, and then extracted with dichloromethane. The collected organic phase was dried over anhydrous sodium sulfate, filtered, and then dried under reduced pressure. The crude product was separated by neutral alumina column chromatography (eluent: dichloromethane / ethanol = 20:1, v / v) to obtain a purple solid SeR1 (124 mg, yield 62%). 1 H-NMR (600 MHz, DMSO-d6) δ (ppm): δ 8.85 (d, J = 5.0 Hz, 2H), 7.78 (d, J = 2.6 Hz, 2H),7.49 (d, J = 5.0 Hz, 2H), 7.16 (d, J = 9.8 Hz, 2H), 7.08 (dd, J 1 = 2.6Hz, J 2 = 9.8 Hz, 2H), 3.24 (s, 12H).ESI-MS: [M] + Calcd for 408.097, Found 408.097.

[0020] Example 2 Synthesis of Selenium-Rhodamine Photosensitizer SeR2 The synthesis process of the first 4 steps is the same as that of Example 1, and the synthesis of the 5th step is as follows: Under nitrogen protection, intermediate 4 (268.8 mg, 0.6 mmol) was dissolved in dry tetrahydrofuran (10 mL), cooled to -78 °C in a liquid nitrogen acetone bath, and then a 1.3 mol / L tert-butyl lithium tetrahydrofuran solution (1.85 mL, 2.40 mmol) was slowly added dropwise, and the reaction was stirred at -78 °C for 1 hour. Then 3-methylisonicotinic acid methyl ester (181.3 mg, 1.2 mmol) was added dropwise, reacted at -78 °C for 30 minutes, and then warmed to room temperature and stirred overnight. Subsequently, the reaction was quenched with 10 mL of 2 mol / L dilute hydrochloric acid aqueous solution, and then stirred at room temperature for 30 minutes. Saturated ammonium chloride aqueous solution was added for dilution, and then extracted with dichloromethane. The collected organic phase was dried over anhydrous sodium sulfate, filtered, and then dried under reduced pressure. The crude product was separated by neutral alumina column chromatography (eluent: dichloromethane / ethanol = 20:1, v / v) to obtain a purple solid SeR2 (177 mg, yield 70%). 1 HNMR (600 MHz, DMSO- d 6) δ 8.74 (s, 1H), 8.66 (d, J = 4.9 Hz, 1H), 7.76 (m, 2H), 7.35 (d, J = 4.9 Hz, 1H), 7.09 (m, 4H), 3.23 (s, 12H), 1.92 (s, 3H). ESI-MS:[M] + Calcd for 422.113, Found 422.110.

[0021] Example 3 Determination of Photophysical Properties of Selenium-Rhodamine Photosensitizer SeR1 (1) Absorption and emission spectra of selenium-rhodamine photosensitizer SeR1 in different solvents SeR1 was prepared into a 2 mmol / L stock solution in DMF, 2 μL of the stock solution was taken into a cuvette, and diluted to 2 mL with different solvents to obtain a concentration of 2 μmol / L -1 The photophysical properties of SeR1 were measured in dichloromethane, acetonitrile, methanol and PBS buffer solutions, and their normalized absorption and emission spectra were given, as shown in Figure 2. Fig.13 , 14 , as shown in Table 1.

[0022] Table 1 Photophysical properties of selenium-rhodamine photosensitizer SeR1 in various solvents (2) Determination of singlet oxygen yield of selenium-rhodamine photosensitizer SeR1 in aqueous phase 9,10-Anthracenediyl-bis(methylene)-dimalonic acid (ABDA) was used as 1 O2 capture agent, with commercial dye Rose Bengal as reference (in PBS, Φ Δ =0.75), the singlet oxygen yield of SeR1 was tested. After adding 2 μM SeR1 to the PBS solution containing ABDA, the singlet oxygen yield of SeR1 was tested at a power of 5 mW / cm 2 Under the 565 nm LED light source, the absorbance of ABDA at 380 nm decreased regularly (e.g. Fig.15 ), the slope of the curve of ABDA absorbance (380 nm) versus time (as shown in Fig.16 As shown in the figure, it can be judged that SeR1 has the ability to generate singlet oxygen, and it is significantly higher than Rose Bengal. The singlet oxygen yield of SeR1 in the corresponding solvent is calculated according to the formula ( Φ Δ ): ; Where k is the slope of the curve of ABDA absorbance at 380 nm versus time under laser irradiation (565 nm, 5 mW·cm -2 , tested every 30s). F is the absorption correction factor, specifically F = 1-10 -OD (OD is the mean absorbance of the photosensitizer at 565 nm).

[0023] The singlet oxygen quantum yield of SeR1 was calculated by the formula ( Φ Δ ) was 90.6%, which indicates that SeR1 can be used as a highly efficient photosensitizer in photodynamic therapy related research.

[0024] (3) Determination of the solubility of selenium-rhodamine photosensitizer SeR1 in aqueous phase The solubility of SeR1 in 10 mM PBS solution was tested. Fig. 20 , 21 As shown, it was found that in the concentration range of 0-40 μM, the absorbance of SeR1 at 590 nm showed a good linear relationship with the concentration (Pearson coefficient was 0.997), indicating that SeR1 has good water solubility.

[0025] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A novel selenium-rhodamine photosensitizer, characterized in that: The general structural formula of the selenium-rhodamine photosensitizer is as follows: ； wherein R1 and R2 are each independently selected from any one of H, C1-10 straight-chain alkyl, branched alkyl, and benzyl; or R1 forms a 6-membered nitrogen-containing heterocyclic ring with the N, C1 and C3 to which it is connected or with the N, C4 and C5 to which it is connected, and / or R2 forms a 6-membered nitrogen-containing heterocyclic ring with the N, C1 and C2 to which it is connected or with the N, C5 and C6 to which it is connected; X - Including F - , Cl - Br - ,I - 、ClO4 - 、CH3COO - CF3COO - Any one of .

2. A method for synthesizing the novel selenium-rhodamine photosensitizer as claimed in claim 1, characterized in that: The steps include: Step 1, Synthesis of Intermediate 1 3-iodoaniline and potassium carbonate were dissolved in anhydrous acetonitrile, and a halogenated hydrocarbon was added thereto at room temperature, and then the mixture was heated to 85°C and refluxed for reaction for 12 hours. After the reaction was completed, the mixture was cooled and filtered to remove the remaining potassium carbonate. The filtrate was diluted with water and extracted with dichloromethane, and the organic phase was collected and dried over anhydrous sodium sulfate. After the solvent was spin-dried, the crude product was separated by column chromatography to obtain a colorless oily intermediate compound 1; Step 2: Synthesis of Intermediate 2 The intermediate 1 was dissolved in dry dimethyl sulfoxide, potassium phosphate, selenium powder and a catalytic amount of cuprous iodide were added thereto, and the mixture was heated to 110°C under nitrogen protection for 12 hours. After the reaction was completed and cooled to room temperature, an appropriate amount of water was added to the reaction system, and the reaction system was filtered to remove the potassium phosphate and selenium powder remaining in the reaction, and then extracted with dichloromethane three times. The collected organic phase was dried over anhydrous sodium sulfate, filtered, and then dried under reduced pressure. The crude product was separated by column chromatography to obtain an orange-red oily liquid 2; Step 3: Synthesis of Intermediate 3 The intermediate 2 was dissolved in dry dimethyl sulfoxide, and the intermediate 1, potassium carbonate, reduced iron powder and a catalytic amount of copper sulfide were added thereto. The mixture was heated to 100°C under nitrogen protection for 6 hours. After the reaction was completed, the mixture was cooled to room temperature, and the reaction solution was diluted with an appropriate amount of dichloromethane. The reaction solution was filtered under reduced pressure through diatomaceous earth to remove the potassium carbonate, reduced iron powder and copper sulfide remaining in the reaction. Then, 3 times the volume of water was added to the filtrate, and the mixture was extracted with dichloromethane. The collected organic phase was dried over anhydrous sodium sulfate, filtered, and then dried under reduced pressure. The crude product was separated by column chromatography to obtain a light yellow solid compound 3. Step 4: Synthesis of Intermediate 4 Under ice bath conditions, the intermediate 3 was dissolved in dry N, N-dimethylformamide, and a DMF solution containing N-bromosuccinimide was added through a dropping funnel within 10 minutes, and then reacted at room temperature for 6 hours. An appropriate amount of distilled water was added to the system to quench the reaction, and then diluted with brine, followed by extraction with ethyl acetate three times. The collected organic phase was dried over anhydrous sodium sulfate, filtered, and then dried under reduced pressure. The crude product was separated by column chromatography to obtain a white solid compound 4; Step 5: Synthesis of Selenium-Rhodamine Photosensitizer Under nitrogen protection, the intermediate 4 is dissolved in tetrahydrofuran, cooled to -78°C in a liquid nitrogen acetone bath, and then tert-butyl lithium tetrahydrofuran solution is added dropwise within 10 minutes, the reaction is maintained at -78°C and stirred for 1 hour, and then methyl isonicotinate or its derivative is added dropwise, and the reaction is carried out at -78°C for 30 minutes and then warmed to room temperature and stirred overnight. The reaction is quenched with a 2 mol / L dilute hydrochloric acid aqueous solution, and then stirred at room temperature for 30 minutes, and a saturated ammonium chloride aqueous solution is added for dilution, and then extracted with dichloromethane. The collected organic phase is dried over anhydrous sodium sulfate, filtered, and then dried under reduced pressure. The crude product was separated by neutral alumina column chromatography and further crystallized with a mixed solvent of ether and ethanol to obtain pure selenium-rhodamine photosensitizer.

3. The method for synthesizing a novel selenium-rhodamine photosensitizer according to claim 2, characterized in that: In the first step, the halogenated hydrocarbon includes bromoalkane or iodoalkane; the molar ratio of the 3-iodoaniline, halogenated hydrocarbon and potassium carbonate is 1:2.2:2.

2.

4. The method for synthesizing a novel selenium-rhodamine photosensitizer according to claim 2, characterized in that: In the second step, the molar ratio of the intermediate 1, potassium phosphate, selenium powder and cuprous iodide is 1:3:3:0.

1.

5. The method for synthesizing a novel selenium-rhodamine photosensitizer according to claim 2, characterized in that: In the third step, the molar ratio of intermediate 1, intermediate 2, potassium carbonate, reduced iron powder and copper sulfide is 1:1:2:1.2:0.

1.

6. The method for synthesizing a novel selenium-rhodamine photosensitizer according to claim 2, characterized in that: In the fourth step, the molar ratio of the intermediate 3 to N-bromosuccinimide is 1:2.

2.

7. The method for synthesizing a novel selenium-rhodamine photosensitizer according to claim 2, characterized in that: In the fifth step, the molar ratio of the intermediate 4, tert-butyl lithium, methyl isonicotinate or its derivative is 1:4:2.

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