Synthesis of near-infrared photodynamic sensitizers platinum complexes and their application in pharmaceutical field
By synthesizing a platinum complex of near-infrared photodynamic sensitizer, the shortcomings of visible light photosensitizers in the treatment of deep tissue tumors have been overcome, achieving deeper tissue penetration and more efficient cancer cell killing effects.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- SHENZHEN UNIV
- Filing Date
- 2023-09-28
- Publication Date
- 2026-06-16
Smart Images
Figure CN117534711B_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of pharmaceutical chemistry, and in particular to the synthesis of platinum complexes of near-infrared photodynamic sensitizers and their application in the pharmaceutical field. Background Technology
[0002] In recent years, cancer has become a major disease threatening human life and health, and is one of the leading causes of death worldwide. In 2021, there were more than 20 million new cancer cases globally. Platinum-based anti-tumor drugs have been used for various types of tumors due to their broad anti-tumor spectrum in clinical practice. Platinum (II) complexes such as cisplatin, oxaliplatin, and carboplatin are common anti-cancer drugs and have achieved some success in clinical application. However, their significant side effects, adverse tumor accumulation, and drug resistance have hindered their clinical application (Angew. Chem. Int. Ed. 2023, 62, e202301074 (1 of 12)).
[0003] Photodynamic therapy (PDT) is a novel anticancer therapy with significant advantages such as precise spatiotemporal control, non-invasiveness, negligible drug resistance, and few side effects, making it a highly attractive cancer treatment method. Under light irradiation, photosensitizers can be activated to generate large amounts of reactive oxygen species (ROS), leading to cell apoptosis / necrosis. Its reaction mechanism can be divided into two types: Type I mechanism involves the activated photosensitizer (PS) directly participating in electron transfer and reacting with oxygen or biological substrates to form oxygen free radicals, while Type II mechanism involves singlet oxygen (…). 1 O2 is generated by direct energy transfer between the excited photosensitizer and O2. These reactive oxygen species can induce tumor cell death and even trigger an immune response.
[0004] However, most traditional metal complex photosensitizers have relatively short absorption and emission wavelengths, mostly in the visible light region (400-700 nm). Short-wavelength photons have limited tissue penetration depth, causing significant damage to biological tissues and resulting in severe light scattering, which is detrimental to the diagnosis and treatment of diseases in deep tissues. Therefore, there is a need to develop a metal complex photosensitizer with deeper tissue penetration compared to visible light photosensitizers, and significantly reduced scattering and autofluorescence effects from biological tissues.
[0005] Therefore, existing technologies still need to be improved and developed. Summary of the Invention
[0006] In view of the shortcomings of the prior art, the present invention provides the synthesis of near-infrared photodynamic sensitizer platinum complexes and their application in the pharmaceutical field, aiming to solve the problem that existing type I photosensitizers in the visible light region are not conducive to photodynamic therapy of deep tissue tumors.
[0007] Specifically, the technical solution of the present invention is as follows:
[0008] This invention provides a platinum complex of near-infrared photodynamic sensitizer, the chemical structural formula of which is shown below:
[0009]
[0010] Optionally, the near-infrared photodynamic sensitizer platinum complex has an absorption wavelength of 622 nm in tetrahydrofuran solution.
[0011] Optionally, the near-infrared photodynamic sensitizer platinum complex emits at a wavelength of 762 nm in tetrahydrofuran solution.
[0012] The present invention also provides a method for synthesizing the platinum complex of the near-infrared photodynamic sensitizer, comprising the following steps:
[0013] S1. In a mixed solvent of tetrahydrofuran and deionized water, 4-boronic acid triphenylamine, 4,7-dibromo-[1,2,5]thiadiazo[3,4-c]pyridine, potassium carbonate, and tetra(triphenylphosphine)palladium (0) were added. The mixture was heated under reflux for the first time in an inert atmosphere. After purification, the ligand 4,7-bis[-4-(N,N-diphenylamino)phenyl][1,2,5]thiadiazo[3,4-c]pyridine was obtained.
[0014] S2. K2PtCl4 and the ligand are added to a mixed solvent of ethylene glycol ethyl ether and deionized water, and then subjected to a second heating under an inert atmosphere and refluxed. After cooling to room temperature, an intermediate product is obtained.
[0015] S3. Dissolve the intermediate product obtained in step S2 in an organic solvent, add silver trifluoromethanesulfonate, and perform a third heating and reflux under an inert atmosphere. Filter to obtain a dark green filtrate.
[0016] S4. Add 2,2'-bipyridine to the dark green filtrate, and perform a fourth heating under reflux in an inert atmosphere and in the dark to obtain the near-infrared photodynamic sensitizer platinum complex after purification.
[0017] Optionally, in step S1, the molar ratio of 4-boronic acid triphenylamine, 4,7-dibromo-[1,2,5]thiadiazolo[3,4-c]pyridine, potassium carbonate, and tetra(triphenylphosphine)palladium(0) is 2.2:1:5:0.1.
[0018] Optionally, in step S2, the molar ratio of K2PtCl4 to 4,7-bis[-4-(N,N-diphenylamino)phenyl][1,2,5]thiadiazolo[3,4-c]pyridine is 1-1.2:1.
[0019] Optionally, in step S3, the molar ratio of the intermediate product to silver trifluoromethanesulfonate is 1:2-5.
[0020] Optionally, in step S4, the ratio of the theoretical molar amount of solute to the molar amount of 2,2'-bipyridine in the dark green filtrate is 1:1.5-2.
[0021] Optionally, the temperature of the first heating reflux is 80°C, and the time of the first heating reflux is 3-5 hours; and / or, the temperature of the second heating reflux is 115°C-120°C, and the time of the second heating reflux is 8-12 hours; and / or, the temperature of the third heating reflux is 80°C, and the time of the third heating reflux is 4-8 hours; and / or, the temperature of the fourth heating reflux is 80°C, and the time of the fourth heating reflux is 24 hours.
[0022] The present invention further provides the application of the platinum complex of the near-infrared photodynamic sensitizer in the pharmaceutical field, wherein the platinum complex of the near-infrared photodynamic sensitizer is used to prepare drugs for tumor photodynamic therapy.
[0023] Beneficial effects:
[0024] This invention provides a synthesis of a platinum complex of near-infrared photodynamic sensitizer and its application in the pharmaceutical field. Compared with traditional photosensitizers, the platinum complex of near-infrared photodynamic sensitizer obtained by the synthesis method of this invention has deeper tissue penetration and does not produce singlet oxygen in the absence of light. 1 O2 and superoxide anion O2 ·- It exhibits minimal cytotoxicity, showing no significant cytotoxicity against mouse 4T1 breast cancer cells; under 633nm light irradiation, the platinum complex of the near-infrared photodynamic sensitizer can generate a large amount of singlet oxygen. 1 O2 and superoxide anion O2 ·- It can oxidize intracellular reducing substances (such as NADH), thereby disrupting the intracellular redox balance and leading to cancer cell death. It exhibits good anti-tumor activity against mouse 4T1 cells. The platinum complex of the near-infrared photodynamic sensitizer has an IC50 of 0.98 μM against mouse 4T1 breast cancer cells, showing excellent anti-tumor effects. It is expected to be used in the field of tumor drug preparation to achieve highly efficient photodynamic therapy for deep tumor tissues. Attached Figure Description
[0025] Figure 1 The ligand 4,7-bis[-4-(N,N-diphenylamino)phenyl][1,2,5]thiadiazo[3,4-c]pyridine synthesized in the embodiments of the present invention... 1 H NMR spectrum.
[0026] Figure 2 The near-infrared photodynamic sensitizer platinum complex provided in the embodiments of the present invention 1 H NMR spectrum.
[0027] Figure 3 The ultraviolet-visible absorption spectrum of the near-infrared photodynamic sensitizer platinum complex provided in the embodiments of the present invention.
[0028] Figure 4 The fluorescence emission spectrum of the near-infrared photodynamic sensitizer platinum complex provided in the embodiments of the present invention.
[0029] Figure 5 The near-infrared photodynamic sensitizer platinum complex provided in this embodiment of the invention operates under illumination conditions (633 nm, 45.9 mW cm⁻¹). -2 ) 9,10-Anthracenediyl-bis(methylene)dimalonic acid (ABDA) was used as 1 UV-Vis absorption spectrum of the O2 probe.
[0030] Figure 6 The near-infrared photodynamic sensitizer platinum complex provided in this embodiment of the invention operates under illumination conditions (633 nm, 45.9 mW cm⁻¹). -2 Dihydrorhodamine 123 (DHR123) was used as O2. ·- Fluorescence spectrum of the probe.
[0031] Figure 7 The platinum complex near-infrared photodynamic sensitizer provided in this embodiment of the invention operates under illumination (633 nm, 45.9 mW / cm²). -2 Effects of exposure to light (0.5 h) and darkness on the activity of mouse 4T1 breast cancer cells. Detailed Implementation
[0032] This invention provides the synthesis of platinum complexes for near-infrared photodynamic sensitizers and their application in the pharmaceutical field. To make the objectives, technical solutions, and effects of this invention clearer and more explicit, the invention is further described in detail below. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the scope of protection of the invention.
[0033] This invention provides a platinum complex of near-infrared photodynamic sensitizer, the chemical structural formula of which is shown below:
[0034]
[0035] In this platinum complex, the benzene ring and pyridine structure bonded to the Pt atom exhibit strong polarization properties, triggering intermolecular interactions such as short-distance contact and π-π stacking between heteroatoms, which facilitates the formation of a highly ordered crystal structure. In the platinum(II) complex, the triphenylamine structure serves as the electron-donating unit, and pyridithiadiazole (PT) acts as the acceptor unit. PT possesses strong electron-withdrawing properties and good coplanarity, enabling the polymer backbone to have higher electron affinity and a narrower optical band gap, emitting red light with greater penetration depth.
[0036] In some embodiments, the near-infrared photodynamic sensitizer platinum complex has an absorption wavelength of 622 nm in tetrahydrofuran solution.
[0037] In some embodiments, the near-infrared photodynamic sensitizer platinum complex emits at a wavelength of 762 nm in tetrahydrofuran solution.
[0038] The emission wavelength of the platinum complex of the near-infrared photodynamic sensitizer is in the near-infrared I region, enabling deep penetration into tissues.
[0039] This invention also provides a method for synthesizing the platinum complex of the near-infrared photodynamic sensitizer, comprising the following steps:
[0040] S1. In a mixed solvent of tetrahydrofuran and deionized water, 4-boronic acid triphenylamine, 4,7-dibromo-[1,2,5]thiadiazo[3,4-c]pyridine, potassium carbonate, and tetra(triphenylphosphine)palladium (0) were added. The mixture was heated under reflux for the first time in an inert atmosphere and purified by silica gel column chromatography to obtain the ligand 4,7-bis[-4-(N,N-diphenylamino)phenyl][1,2,5]thiadiazo[3,4-c]pyridine.
[0041] S2. K2PtCl4 and the ligand are added to a mixed solvent of ethylene glycol ethyl ether and deionized water, and heated for a second time under an inert atmosphere. After cooling to room temperature, an intermediate product is obtained.
[0042] S3. Dissolve the intermediate product obtained in step S2 in an organic solvent, add silver trifluoromethanesulfonate, and perform a third heating and reflux under an inert atmosphere. Filter to obtain a dark green filtrate.
[0043] S4. Add 2,2'-bipyridine to the dark green filtrate, and perform a fourth heating under an inert atmosphere and in the dark. Purify by silica gel column chromatography to obtain the near-infrared photodynamic sensitizer platinum complex Pt-TPA.
[0044] The inert atmosphere in the above steps can be nitrogen, but is not limited to this.
[0045] In some embodiments, in step S1, the molar ratio of 4-boronic acid triphenylamine, 4,7-dibromo-[1,2,5]thiadiazolo[3,4-c]pyridine, potassium carbonate, and tetra(triphenylphosphine)palladium(O) is 2.2:1:5:0.1.
[0046] In some embodiments, the temperature of the first heating reflux is 80°C, and the time of the first heating reflux is 3-5 hours.
[0047] In some embodiments, in step S2, the molar ratio of K2PtCl4 to 4,7-bis[-4-(N,N-diphenylamino)phenyl][1,2,5]thiadiazolo[3,4-c]pyridine is 1-1.2:1.
[0048] In a preferred embodiment, the molar ratio of K2PtCl4 to 4,7-bis[-4-(N,N-diphenylamino)phenyl][1,2,5]thiadiazolo[3,4-c]pyridine is 1:1.
[0049] In some embodiments, the temperature of the second heating reflux is 115°C-120°C, and the time of the second heating reflux is 8-12 hours.
[0050] In a preferred embodiment, the temperature of the second heating reflux is 120°C, and the time of the second heating reflux is 9 hours.
[0051] In some embodiments, in step S3, the molar ratio of the intermediate product to silver trifluoromethanesulfonate is 1:2-5.
[0052] In a preferred embodiment, the molar ratio of the intermediate product to silver trifluoromethanesulfonate is 1:5. The organic solvent for dissolving the intermediate product includes, but is not limited to, acetonitrile, and may also be toluene, N,N-dimethylformamide, etc.
[0053] In some embodiments, the temperature of the third heating reflux is 80°C, and the time of the third heating reflux is 4-8 hours.
[0054] In some embodiments, in step S4, the ratio of the theoretical molar amount of solute to the molar amount of 2,2'-bipyridine in the dark green filtrate is 1:1.5-2.
[0055] In some embodiments, the temperature of the fourth heating reflux is 80°C, and the time of the fourth heating reflux is 24 hours.
[0056] This invention also provides an application of a platinum near-infrared photodynamic sensitizer complex in the pharmaceutical field, whereby the platinum near-infrared photodynamic sensitizer complex is used to prepare a drug for photodynamic therapy of tumors. This platinum near-infrared photodynamic sensitizer complex exhibits deeper tissue penetration and does not produce singlet oxygen in the absence of light. 1 O2 and superoxide anion O2 ·- It showed no significant cytotoxicity against mouse 4T1 breast cancer cells; however, it generated large amounts of type I and type II reactive oxygen species, i.e., singlet oxygen, under 633nm light irradiation. 1 O2 and superoxide anion O2 ·- It can oxidize intracellular reducing substances (such as NADH), thereby disrupting the intracellular redox balance and exhibiting good antitumor activity against mouse 4T1 cells.
[0057] The present invention will be further described below with reference to specific embodiments.
[0058] The equipment used in this embodiment is all conventional experimental equipment, and the materials and reagents used are all commercially available unless otherwise specified.
[0059] Example 1: Synthesis of Pt-TPA, a platinum complex of near-infrared photodynamic sensitizer
[0060] The synthesis of the near-infrared photodynamic sensitizer platinum complex Pt-TPA is carried out as follows:
[0061] (1) Take a 50 mL reaction tube and add 2.2 equiv. of 4-boronic acid triphenylamine, 1 equiv. of 4,7-dibromo-[1,2,5]thiadiazo[3,4-c]pyridine, 5 equiv. of potassium carbonate, and 0 equiv. of tetra(triphenylphosphine)palladium(0) (0.1 equiv.) to a 6 mL mixed solvent of tetrahydrofuran and deionized water in a volume ratio of 4:1. Place the reaction mixture under an inert atmosphere and heat under reflux at 80 °C for 5 hours. After the reaction, cool to room temperature, remove the solvent by rotary evaporation, and purify the ligand L1 by silica gel column chromatography using petroleum ether and dichloromethane (1:5) as the developing solvent to obtain 4,7-bis[-4-(N,N-diphenylamino)phenyl][1,2,5]thiadiazo[3,4-c]pyridine in a yield of 69%.
[0062] The 1H NMR spectrum of the product is as follows Figure 1 As shown: 1 H NMR (500MHz, CDCl3) δ8.78 (s, 1H), 8.57 (d, J = 8.6Hz, 2H), 7.97 -7.90(m,2H),7.34(td,J=7.4,5.4Hz,8H),7.27-7.20(m,12H),7.12(dt,J=14.6,7.3Hz,4H).
[0063] The equations for the above chemical reactions are as follows:
[0064]
[0065] (2) Take a 50 mL reaction tube, add potassium tetrachloroplatinate K2PtCl4 (1 equiv.) and ligand L1 (1 equiv.) to a mixed solvent of 4 mL ethylene glycol ethyl ether and a small amount of deionized water (400 μL), heat and reflux at 120 °C for 9 hours in an inert atmosphere, cool to room temperature, precipitate the product with ether, wash with water and ether and dry to obtain a solid product;
[0066] (3) Dissolve the solid product (1 equiv.) obtained in (2) in 10 mL of acetonitrile, add excess silver trifluoromethanesulfonate (5 equiv.), heat and reflux at 80 °C under an inert atmosphere for 8 h, filter off the AgCl precipitate, retain the dark green filtrate, and calculate the molar yield in the filtrate according to the 100% theoretical yield to obtain the corresponding theoretical molar yield.
[0067] (4) Add 2,2'-bipyridine (2 equiv.) to the green filtrate obtained in (3), heat and reflux at 80°C for 24 h under an inert atmosphere, cool to room temperature after reaction, remove solvent by rotary evaporation, separate and purify by silica gel chromatography column using dichloromethane and methanol as developing solvent, and finally dry in vacuum to obtain the near-infrared photodynamic sensitizer platinum complex Pt-TPA.
[0068] The chemical reaction equations for (2)-(4) are as follows:
[0069]
[0070] The 1H NMR spectrum of the product is as follows Figure 2 As shown: 1 H NMR(500MHz,DMSO-d6)δ9.60(s,1H),8.77(d,J=8.0Hz,1H),8.32(dd,J=5.0,2.0Hz,1H),8.02-7.90(m,2H),7.85(d,J=8.0Hz,1H) ,7.69(ddd,J=8.9,7.1,2.0Hz,1H),7.44(d,J=8.4Hz,1H),7.40-7.31(m,4H),7.10(t,J=8.2Hz,10H),6.92(dd,J=7.2,5.0Hz,1H).
[0071] The UV absorption and fluorescence emission spectra of the near-infrared photodynamic sensitizer platinum complex Pt-TPA in tetrahydrofuran solution were measured using a UV-Vis spectrophotometer. Figure 3 and Figure 4As shown, the platinum complex of the near-infrared photodynamic sensitizer has a maximum absorption wavelength of 622 nm and a maximum emission wavelength of 762 nm in tetrahydrofuran solution, which is in the near-infrared I region, enabling deep penetration into tissues.
[0072] Example 2: Near-infrared photodynamic sensitizer platinum complex Pt-TPA photoactivated release 1 O2
[0073] 9,10-Anthracenediyl-bis(methylene)dimalonic acid (ABDA) was used as a precipitant for detecting singlet oxygen. 1 An O2 probe was used to detect the ability of the near-infrared photodynamic sensitizer platinum complex Pt-TPA to generate singlet oxygen under illumination. ABDA can selectively react with... 1 The O2 reaction reduces its ultraviolet absorbance. A mixed solution of 20 μM near-infrared photodynamic sensitizer platinum complex Pt-TPA and 100 μM ABDA was placed at 633 nm (45.9 mW cm⁻¹). -2 Under illumination, the ultraviolet absorption of ABDA was measured every 3 minutes using an ultraviolet-visible spectrophotometer.
[0074] like Figure 5 As shown, under light irradiation, the ultraviolet absorption value of ANDA gradually decreased, and at 21 minutes, the absorption value dropped to almost zero, indicating that under light conditions, the near-infrared photodynamic sensitizer platinum complex Pt-TPA has a good ability to release singlet oxygen.
[0075] Example 3: Near-infrared photodynamic sensitizer platinum complex Pt-TPA photoactivated release of O2 ·-
[0076] The superoxide anion O2 generated by the near-infrared photodynamic sensitizer platinum complex Pt-TPA under illumination was detected using a dihydrorhodamine 123 (DHR123) fluorescent probe. ·- The ability. O2 ·- DHR123 can be oxidized to the highly fluorescent derivative rhodamine 123.
[0077] A mixed solution of 20 μM near-infrared photodynamic sensitizer platinum complex Pt-TPA and 10 μM DHR123 was placed at 633 nm (45.9 mW cm⁻¹). -2 Under illumination, the fluorescence emission of DHR123 was measured every 30 seconds using a fluorophotometer.
[0078] like Figure 6 As shown, within a certain illumination time, the fluorescence significantly increases with increasing illumination time, indicating that the near-infrared photodynamic sensitizer platinum complex Pt-TPA generates a large amount of O2 after illumination. ·- .
[0079] Example 4: Cytotoxicity of near-infrared photodynamic sensitizer platinum complex Pt-TPA on mouse breast cancer cells
[0080] Mouse breast cancer cells (4T1 cells) were seeded in 96-well plates and cultured in DMEM medium for 24 hours. After cell morphology recovery, the cells were incubated for 2 hours in medium containing different concentrations of the near-infrared photodynamic sensitizer platinum complex Pt-TPA (0 μM, 0.31 μM, 0.63 μM, 1.25 μM, 2.5 μM, 5 μM, 10 μM, 20 μM). The drug-containing medium was then removed, and fresh medium was added. Cells were then incubated in the dark and at 633 nm (45.9 mW cm⁻¹) for 2 hours. -2 The cells were treated under light for 0.5 hours. Then, they were incubated in an incubator for 44 hours. After that, 25 μL of PBS solution containing thiazolyl blue (5 mg / mL) was added to each well. -1 Continue incubation for 4 hours, remove the culture medium, add 150 μL of DMSO to each well, place the 96-well plate on a shaker and shake for 15 minutes, and finally use a microplate reader to read the changes in optical density (OD) at 490 nm to obtain the cell viability.
[0081] like Figure 7 As shown, under dark conditions, the near-infrared luminescent platinum complex Pt-TPA showed no significant toxicity to 4T1 cells (IC50 > 20 μM). However, under light conditions, the cell viability of 4T1 cells was significantly reduced. The near-infrared photodynamic sensitizer platinum complex Pt-TPA exhibited completely different cytotoxicity under light conditions compared to those under dark conditions (IC50 reached 0.98 μM), indicating that the near-infrared photodynamic sensitizer platinum complex Pt-TPA has excellent antitumor activity under photoexcitation conditions.
[0082] In summary, the near-infrared photodynamic sensitizer platinum complex provided by this invention has deeper tissue penetration and does not generate singlet oxygen in the absence of light. 1 O2 and superoxide anion O2 ·- It exhibits minimal cytotoxicity, showing no significant cytotoxicity against mouse 4T1 breast cancer cells; under 633nm light irradiation, the platinum complex of the near-infrared photodynamic sensitizer can generate a large amount of singlet oxygen. 1 O2 and superoxide anion O2 ·- It can oxidize intracellular reducing substances (such as NADH), thereby disrupting the intracellular redox balance and leading to cancer cell death. It exhibits good anti-tumor activity against mouse 4T1 cells. The platinum complex of the near-infrared photodynamic sensitizer has an IC50 of 0.98 μM against mouse 4T1 breast cancer cells, showing excellent anti-tumor effects and enabling highly efficient treatment of deep tumor tissues.
[0083] It should be understood that the application of the present invention is not limited to the examples above. Those skilled in the art can make improvements or modifications based on the above description, and all such improvements and modifications should fall within the protection scope of the appended claims.
Claims
1. A platinum complex of near-infrared photodynamic sensitizer, characterized in that, The chemical structural formula of the platinum complex of the near-infrared photodynamic sensitizer is shown below:
2. The near-infrared photodynamic sensitizer platinum complex according to claim 1, characterized in that, The near-infrared photodynamic sensitizer platinum complex has an absorption wavelength of 622 nm in tetrahydrofuran solution.
3. The near-infrared photodynamic sensitizer platinum complex according to claim 1, characterized in that, The near-infrared photodynamic sensitizer platinum complex emits at a wavelength of 762 nm in tetrahydrofuran solution.
4. The method for synthesizing the platinum complex of the near-infrared photodynamic sensitizer as described in any one of claims 1 to 3, characterized in that, Including the following steps: S1. In a mixed solvent of tetrahydrofuran and deionized water, 4-boronic acid triphenylamine, 4,7-dibromo-[1,2,5]thiadiazo[3,4-c]pyridine, potassium carbonate, and tetra(triphenylphosphine)palladium (0) were added. The mixture was heated under reflux for the first time in an inert atmosphere. After purification, the ligand 4,7-bis[-4-(N,N-diphenylamino)phenyl][1,2,5]thiadiazo[3,4-c]pyridine was obtained. S2. K2PtCl4 and the ligand are added to a mixed solvent of ethylene glycol ethyl ether and deionized water, and then subjected to a second heating under an inert atmosphere and refluxed. After cooling to room temperature, an intermediate product is obtained. S3. Dissolve the intermediate product obtained in step S2 in an organic solvent, add silver trifluoromethanesulfonate, perform a third heating and reflux under an inert atmosphere, filter, and obtain a dark green filtrate. S4. Add 2,2'-bipyridine to the dark green filtrate, and perform a fourth heating under reflux in an inert atmosphere and in the dark to obtain the near-infrared photodynamic sensitizer platinum complex after purification.
5. The method for synthesizing the near-infrared photodynamic sensitizer platinum complex according to claim 4, characterized in that, In step S1, the molar ratio of 4-boronic acid triphenylamine, 4,7-dibromo-[1,2,5]thiadiazolo[3,4-c]pyridine, potassium carbonate, and tetra(triphenylphosphine)palladium(0) is 2.2:1:5:0.
1.
6. The method for synthesizing the near-infrared photodynamic sensitizer platinum complex according to claim 4, characterized in that, In step S2, the molar ratio of K2PtCl4 to 4,7-bis[-4-(N,N-diphenylamino)phenyl][1,2,5]thiadiazolo[3,4-c]pyridine is 1-1.2:
1.
7. The method for synthesizing the near-infrared photodynamic sensitizer platinum complex according to claim 4, characterized in that, In step S3, the molar ratio of the intermediate product to silver trifluoromethanesulfonate is 1:2-5.
8. The method for synthesizing the near-infrared photodynamic sensitizer platinum complex according to claim 4, characterized in that, In step S4, the ratio of the theoretical molar amount of solute to the molar amount of 2,2'-bipyridine in the dark green filtrate is 1:1.5-2.
9. The method for synthesizing the near-infrared photodynamic sensitizer platinum complex according to claim 4, characterized in that, The first heating and reflux temperature is 80℃, and the first heating and reflux time is 3-5h; and / or, the second heating and reflux temperature is 115℃-120℃, and the second heating and reflux time is 8-12h; and / or, the third heating and reflux temperature is 80℃, and the third heating and reflux time is 4-8h; and / or, the fourth heating and reflux temperature is 80℃, and the fourth heating and reflux time is 24h.
10. The application of a near-infrared photodynamic sensitizer platinum complex in the pharmaceutical field, characterized in that, The platinum complex of the near-infrared photodynamic sensitizer as described in any one of claims 1 to 3 is used to prepare a drug for tumor photodynamic therapy.