Ionic iridium complex photosensitizer as well as preparation method and application thereof

Abstract

The invention discloses an ionic iridium complex photosensitizer as well as a preparation method and application thereof, belongs to the technical field of metal complex photosensitizer medicines, and provides four ionic iridium complex photosensitizers with excellent treatment effects. The invention further provides a preparation method of the four ionic iridium complexes and application of the ionic iridium complexes in tumor photodynamic therapy drugs. The triplet excited state energy level of the prepared ionic iridium complex photosensitizer can be well matched with the excited state energy level of oxygen, and meanwhile, the ionic iridium complex photosensitizer has a relatively long triplet excited state life, so that the singlet oxygen yield is relatively high, and the ionic iridium complex photosensitizer shows excellent phototoxicity in mouse breast cancer cells; wherein the tumor inhibition coefficient of Ir-3 in a mouse body is as high as 79.87%, the growth of tumors can be inhibited and eliminated, and an excellent photodynamic therapy effect is achieved.

Description

Technical Field

[0001] The invention belongs to the technical field of metal complex photosensitizer drugs, and in particular relates to an ionic iridium complex photosensitizer and a preparation method and application thereof. Background Art

[0002] Cancer is a common major disease. Compared with traditional chemotherapy, surgery and radiotherapy, photodynamic therapy has the advantages of being non-invasive, safe and selective, and is widely considered to be an effective cancer treatment technology. Photodynamic therapy has become a well-established treatment method and is widely used in clinical medicine, biomedicine and life sciences. Photodynamic therapy refers to the process in which a light source excites a photosensitizer to produce reactive oxygen species, which destroys the normal functions of cancer cells and causes cancer cell death. To date, type II photodynamic therapy has been widely reported, and its mechanism is that the ground state photosensitizer is excited by the light source to become an excited state photosensitizer, which then transfers energy to the surrounding oxygen molecules, thereby producing singlet oxygen and inducing cell death.

[0003] Benefiting from the development of synthetic chemistry, many types of photosensitizers have been designed and synthesized. Among them, transition metal complex photosensitizers have attracted much attention, such as ruthenium (Ru) complexes, platinum (Pt) complexes, iridium (Ir) complexes, etc. Among them, iridium complexes have the advantages of long fluorescence lifetime, good chemical stability, and adjustable photophysical properties, and can be used to design a variety of highly sensitive tumor imaging fluorescent probes and photodynamic therapy photosensitizers. Summary of the invention

[0004] The invention provides an ionic iridium complex photosensitizer and a preparation method and application thereof. The prepared ionic iridium complex photosensitizer has a high singlet oxygen yield, can better inhibit and eliminate tumor growth, and has an excellent photodynamic therapy effect.

[0005] To achieve the above objectives, the present invention adopts the following technical solutions: Ionic iridium complex photosensitizers are named Ir-1, Ir-2, Ir-3, and Ir-4, and their chemical structures are as follows: .

[0006] The preparation method of the above-mentioned ionic iridium complex photosensitizer comprises the following steps: (1) The precursor, benzothiophene-2-boronic acid and catalyst were dissolved in a solvent, the reaction system was kept oxygen-free, and the Suzuki coupling reaction was carried out at 100 °C in an alkaline environment for 16 h; (2) A mixture of 1,10-phenanthroline-5,6-dione, ammonium acetate, aniline and p-hydroxybenzaldehyde was dissolved in glacial acetic acid. The reaction system was kept oxygen-free and refluxed at 118 °C overnight. The reaction mixture was cooled to room temperature, poured into water, and treated with 25% NH3 solution to pH = 6 to produce a thick dark green suspension, which was filtered to obtain 4-(1-phenyl-1) H -imidazole[4,5- f [1,10]phenanthren-2-yl)phenol; (3) dissolving the reaction product obtained in step (1) and iridium trichloride trihydrate in a solvent, keeping the reaction system oxygen-free, reacting at 120° C. for 24 hours to obtain the corresponding dimer; (4) The dimer is mixed with 4-(1-phenyl-1) H -imidazole[4,5- f [1,10]phenanthrene-2-yl)phenol was dissolved in a mixed solvent, the reaction system was kept oxygen-free, and the coordination reaction occurred at 120°C for 24 hours. Potassium hexafluorophosphate was added and reacted for 0.5 hours to obtain the target ionic iridium complex photosensitizer.

[0007] In the above steps, the reaction system is oxygen-free and preferably carried out under an argon atmosphere; In step (1), the molar ratio of the precursor to benzothiophene-2-boric acid is 1:(1-1.2); the catalyst is preferably tetrakis(triphenylphosphine)palladium; the molar ratio of the precursor to the catalyst is 1:(0.04-0.08); the solvent is water and 1,4-dioxane, the volume ratio is 1:3, the amount ratio of the precursor to water is 1 g:30 mL; the base used in the alkaline environment is potassium carbonate; the molar ratio of the precursor to potassium carbonate is 1:(5-5.2); The molar ratio of 1,10-phenanthroline-5,6-dione, aniline, p-hydroxybenzaldehyde and ammonium acetate in step (2) is 1:(1-1.2):1:12; the amount ratio of 1,10-phenanthroline-5,6-dione to glacial acetic acid is 1 g:35 mL; the concentration of ammonia water used is 25%; In step (3), the molar ratio of the reaction product obtained in step (1) to iridium trichloride trihydrate is 1:(0.4-0.6); the reaction solvent is water and 2-ethoxyethanol, the volume ratio is 1:3; the amount ratio of iridium trichloride trihydrate to water is 1 g:20 mL; Step (4) The dimer is reacted with 4-(1-phenyl-1) H -imidazole[4,5- fThe molar ratio of the dimer to potassium hexafluorophosphate is 1:(3.5-4); the dosage ratio of the dimer to 2-ethoxyethanol is 1 g:80 mL; When preparing Ir-1, the precursor is 2-chloropyridine, and the reaction product of step (1) is 2-(2-pyridyl)benzothiophene; When preparing Ir-2, the precursor is 1-chloroisoquinoline, and the reaction product of step (1) is 1-benzothiophene-2-ylisoquinoline; When preparing Ir-3, the precursor is 2-chloroquinoline, and the reaction product of step (1) is 2-(1-benzothiophen-2-yl)quinoline; When preparing Ir-4, the precursor is 6-chlorophenanthridine, and the reaction product of step (1) is 6-benzothiophene-2-phenanthridine.

[0008] The above-mentioned ionic iridium complex photosensitizers can all be used for the preparation of tumor photodynamic therapy drugs.

[0009] Beneficial effects: The present invention provides an ionic iridium complex photosensitizer and a preparation method and application thereof, which have the following advantages over the prior art: The synthesis method of the ionic iridium complex of the present invention is simple, the raw materials are easily available, and the purification is convenient and easy to operate; The triplet excited state energy level of the ionic iridium complex of the present invention can be well matched with the excited state energy level of oxygen, and at the same time has a long triplet excited state life span, a high singlet oxygen yield, and excellent photophysical properties; Compared with some neutral complexes, the ionic iridium complex of the present invention has better solubility and biocompatibility, so that it can be well taken up by cells to play a role when applied in the body; The ionic iridium complex of the present invention has a high active oxygen production rate and ultra-high phototoxicity in a phosphate buffer, and can inhibit cancer cell proliferation and kill cancer cells at low concentrations; The ionic iridium complex photosensitizer of the present invention exhibits good therapeutic effects on mouse breast tumors. The tumor inhibition coefficient of the photosensitizer Ir-3 is as high as 79.87%, which can inhibit and eliminate tumor growth. At the same time, its effect is better than that of the commercial photosensitizer Ce6, and it is a candidate material for photosensitizers with excellent photodynamic therapy effects. BRIEF DESCRIPTION OF THE DRAWINGS

[0010] Figure 1 The synthetic route of Ir-1 in the embodiment of the present invention; Figure 2 The synthesis route of Ir-2 in the embodiment of the present invention; Figure 3The synthesis route of Ir-3 in the embodiment of the present invention; Figure 4 The synthesis route of Ir-4 in the embodiment of the present invention; Figure 5 This is a test diagram of the degradation of ABDA by ionic iridium complexes Ir-1, Ir-2, Ir-3, Ir-4 and reference terpyridine ruthenium under the action of laser in the embodiment of the present invention; Figure 6 The results of the cytotoxicity test of ionic iridium complexes Ir-1, Ir-2, Ir-3, and Ir-4 on 4T1 cells in the embodiments of the present invention are shown in FIG. Figure 7 This is a graph showing the inhibition coefficient of ionic iridium complex Ir-3 on mouse breast cancer tumors in an embodiment of the present invention. DETAILED DESCRIPTION

[0011] The present invention is described in detail below with reference to the accompanying drawings and specific embodiments: Example 1

[0012] like Figure 1 As shown, the preparation method of the ionic iridium complex photosensitizer Ir-1 comprises the following steps: 2-Chloropyridine (1 g), benzothiophene-2-boric acid (1.7 g), tetrakis(triphenylphosphine)palladium (0.6 g), potassium carbonate (6.1 g) were added to a 250 mL round-bottom flask, and water (30 mL) and 1,4-dioxane (90 mL) were added. The reaction mixture was protected by argon and the temperature of the reaction solution was 100 °C. The reaction mixture was reacted for 16 h. After the reaction was completed, the mixture was cooled to room temperature, extracted with ethyl acetate and saturated brine, dried over anhydrous sodium sulfate, filtered, and the solvent was removed by vacuum distillation to obtain a crude product, which was purified by column chromatography with the eluent being V (Petroleum ether): V (ethyl acetate) = 20:1, and a white solid was obtained as 2-(2-pyridyl)benzothiophene; 1,10-phenanthroline-5,6-dione (3.15 g, 15 mmol), aniline (1.675 g, 18 mmol), p-hydroxybenzaldehyde (1.952 g, 5 mmol) and ammonium acetate (11.69 g, 180 mmol) were added to a 250 mL round-bottom flask, and 105 mL of glacial acetic acid was added. The reaction mixture was protected by argon and the temperature of the reaction solution was 118 °C for 12 h. After the reaction was completed, it was cooled to room temperature and poured into water (200 mL). It was treated with 25% NH3 solution to pH = 6 to produce a thick dark green suspension, which was filtered to obtain a dark green crude product. It was purified by column chromatography with the eluent being V (Dichloromethane): V(methanol) = 40:1, a white solid was obtained as 4-(1-phenyl-1) H -imidazole[4,5- f [1,10]phenanthren-2-yl)phenol; Iridium trichloride trihydrate (0.5 g) and 2-(2-pyridyl)benzothiophene (0.6 g) were added to a 100 mL round-bottom flask, and 2-ethoxyethanol (30 mL) and water (10 mL) were added. The reaction mixture was kept at 120 °C in an argon atmosphere for 24 h. After the reaction mixture was completely cooled to room temperature, the reaction mixture was slowly poured into a beaker containing 100 mL of water. After stirring for 30 minutes, the mixture was filtered and the residue was dried to obtain a red solid as a dimer. Dimer (0.5 g), 4-(1-phenyl-1) H -imidazole[4,5- f [1,10]phenanthrene-2-yl)phenol (0.37 g) was added to a 100 mL round-bottom flask, and 2-ethoxyethanol (40 mL) was added. The reaction was carried out at 120 °C for 24 h under argon atmosphere. After the reaction was completed, potassium hexafluorophosphate (0.27 g) was added and stirred at normal pressure for 0.5 h. The reaction solution was extracted with ethyl acetate and water, dried over anhydrous sodium sulfate, filtered, and the solvent was removed by vacuum distillation to obtain a crude product, which was purified by column chromatography with the eluent being V (Dichloromethane): V (methanol) = 20:1, the red solid obtained is the ionic iridium complex Ir-1; 1 H NMR (400 MHz, DMSO- d 6) δ10.04 (s, 1H), 9.35 (d, J = 8.2 Hz, 1H), 8.23 ​​(d, J = 5.1 Hz, 1H), 8.14 (dd, J =8.3, 5.2 Hz, 1H), 8.05 (d, J = 4.3 Hz, 1H), 7.97 (t, J = 9.3 Hz, 9H), 7.83 – 7.71(m, 9H), 7.60 – 7.42 (m, 6H), 7.25 (q, J = 8.2 Hz, 3H), 7.02 – 6.87 (m, 6H), 6.78 (d, J = 8.7 Hz, 2H), 6.11 – 5.90 (m, 3H). Example 2

[0013] like Figure 2As shown, the preparation method of the ionic iridium complex photosensitizer Ir-2 comprises the following steps: 1-Chloroisoquinoline (1 g), benzothiophene-2-boric acid (1.2 g), tetrakis(triphenylphosphine)palladium (0.42 g), potassium carbonate (4.23 g) were added to a 250 mL round-bottom flask, and water (30 mL) and 1,4-dioxane (90 mL) were added. The reaction mixture was protected by argon and the temperature of the reaction solution was 100 °C. The reaction mixture was reacted for 16 h. After the reaction was completed, the mixture was cooled to room temperature, extracted with ethyl acetate and saturated brine, dried over anhydrous sodium sulfate, filtered, and the solvent was removed by distillation under reduced pressure to obtain a crude product, which was purified by column chromatography with the eluent being V (Petroleum ether): V (ethyl acetate) = 20:1, and a white solid was obtained as 1-benzothiophen-2-ylisoquinoline; 1,10-phenanthroline-5,6-dione (3.15 g, 15 mmol), aniline (1.675 g, 18 mmol), p-hydroxybenzaldehyde (1.952 g, 5 mmol) and ammonium acetate (11.69 g, 180 mmol) were added to a 250 mL round-bottom flask. After adding 105 mL of glacial acetic acid, the reaction solution was protected by argon and the temperature was 118 °C. The reaction was carried out for 12 h. After the reaction was completed, it was cooled to room temperature and poured into water (200 mL). It was treated with 25% NH3 solution to pH = 6 to produce a thick dark green suspension. The dark green crude product was obtained by filtration and purified by column chromatography. The eluent was V (Dichloromethane): V (methanol) = 40:1, a white solid was obtained as 4-(1-phenyl-1) H -imidazole[4,5- f [1,10]phenanthren-2-yl)phenol; Iridium trichloride trihydrate (0.5 g) and 1-benzothiophene-2-ylisoquinoline (0.738 g) were added to a 100 mL round-bottom flask, and 2-ethoxyethanol (30 mL) and water (10 mL) were added. The reaction mixture was kept at 120 °C under argon atmosphere for 24 h. After the reaction mixture was completely cooled to room temperature, the reaction mixture was slowly poured into a beaker containing 100 mL of water. After stirring for 30 minutes, the mixture was filtered and the residue was dried to obtain a red solid as a dimer. Dimer (0.5 g), 4-(1-phenyl-1) H -imidazole[4,5- f[1,10]phenanthrene-2-yl)phenol (0.337 g) was added to a 100 mL round-bottom flask, and 2-ethoxyethanol (40 mL) was added. The reaction was carried out at 120 °C for 24 h under argon atmosphere. After the reaction was completed, potassium hexafluorophosphate (0.24 g) was added and stirred at normal pressure for 0.5 h. The reaction solution was extracted with ethyl acetate and water, dried over anhydrous sodium sulfate, filtered, and the solvent was removed by vacuum distillation to obtain a crude product, which was purified by column chromatography with the eluent being V (Dichloromethane): V (methanol) = 20:1, the red solid obtained is the ionic iridium complex Ir-2; 1 H NMR (400 MHz, DMSO- d 6) δ10.04 (s, 1H), 9.46 – 9.21 (m, 1H), 9.03 (dd, J = 15.3, 8.5 Hz, 2H), 8.28 –8.18 (m, 1H), 8.16 – 7.85 (m, 8H), 7.85 – 7.61 (m, 6H), 7.57 – 7.33 (m, 7H),7.25 (q, J = 8.2 Hz, 2H), 6.76 (td, J = 9.8, 9.3, 6.6 Hz, 4H), 6.10 (dd, J = 11.6,8.2 Hz, 2H). Example 3

[0014] like Figure 3 As shown, the preparation method of the ionic iridium complex photosensitizer Ir-3 comprises the following steps: 2-Chloroquinoline (1 g), benzothiophene-2-boric acid (1.2 g), tetrakis(triphenylphosphine)palladium (0.42 g), potassium carbonate (4.23 g) were added to a 250 mL round-bottom flask, and water (30 mL) and 1,4-dioxane (90 mL) were added. The reaction mixture was protected by argon and the temperature of the reaction solution was 100 °C. The reaction mixture was reacted for 16 h. After the reaction was completed, the mixture was cooled to room temperature, extracted with ethyl acetate and saturated brine, dried over anhydrous sodium sulfate, filtered, and the solvent was removed by vacuum distillation to obtain a crude product, which was purified by column chromatography with the eluent being V (Petroleum ether): V (ethyl acetate) = 20:1, and a white solid was obtained as 2-(1-benzothiophen-2-yl)quinoline; 1,10-phenanthroline-5,6-dione (3.15 g, 15 mmol), aniline (1.675 g, 18 mmol), p-hydroxybenzaldehyde (1.952 g, 5 mmol) and ammonium acetate (11.69 g, 180 mmol) were added to a 250 mL round-bottom flask, and 105 mL of glacial acetic acid was added. The reaction mixture was protected by argon and the temperature of the reaction solution was 118 °C for 12 h. After the reaction was completed, it was cooled to room temperature and poured into water (200 mL). It was treated with 25% NH3 solution to pH = 6 to produce a thick dark green suspension, which was filtered to obtain a dark green crude product. It was purified by column chromatography with the eluent being V (Dichloromethane): V (methanol) = 40:1, a white solid was obtained as 4-(1-phenyl-1) H -imidazole[4,5- f [1,10]phenanthren-2-yl)phenol; Iridium trichloride trihydrate (0.5 g) and 2-(1-benzothiophene-2-yl)quinoline (0.738 g) were added to a 100 mL round-bottom flask, and 2-ethoxyethanol (30 mL) and water (10 mL) were added. The reaction mixture was kept at 120 °C under argon atmosphere for 24 h. After the reaction mixture was completely cooled to room temperature, the reaction mixture was slowly poured into a beaker containing 100 mL of water. After stirring for 30 minutes, the mixture was filtered and the residue was dried to obtain a red solid as a dimer. Dimer (0.5 g), 4-(1-phenyl-1) H -imidazole[4,5- f [1,10]phenanthrene-2-yl)phenol (0.337 g) was added to a 100 mL round-bottom flask, and 2-ethoxyethanol (40 mL) was added. The reaction was carried out at 120 °C for 24 h under argon atmosphere. After the reaction was completed, potassium hexafluorophosphate (0.24 g) was added and stirred at normal pressure for 0.5 h. The reaction solution was extracted with ethyl acetate and water, dried over anhydrous sodium sulfate, filtered, and the solvent was removed by vacuum distillation to obtain a crude product, which was purified by column chromatography with the eluent being V (Dichloromethane): V (methanol) = 20:1, the red solid obtained is the ionic iridium complex Ir-3; 1 H NMR (400 MHz, DMSO- d 6) δ9.97 (s, 1H), 9.18 (dd, J = 8.3, 1.4 Hz, 1H), 8.74 (dd, J = 5.3, 1.4 Hz, 1H),8.59 (dd, J = 5.2, 1.3 Hz, 1H), 8.53 (d,J = 8.6 Hz, 2H), 8.23 ​​(ddd, J = 19.2, 8.4,5.8 Hz, 3H), 8.10 – 8.02 (m, 2H), 7.87 – 7.78 (m, 3H), 7.68 (ttd, J = 10.7,6.4, 6.0, 2.3 Hz, 5H), 7.40 (dd, J = 8.6, 1.3 Hz, 1H), 7.35 – 7.28 (m, 2H), 7.21 (p, J = 7.2, 6.8 Hz, 4H), 7.01 (d, J = 8.9 Hz, 1H), 6.90 – 6.72 (m, 3H), 6.72 – 6.65 (m, 4H), 6.22 (dd, J = 13.2, 8.2 Hz, 2H). Example 4

[0015] like Figure 4 As shown, the preparation method of the ionic iridium complex photosensitizer Ir-4 comprises the following steps: 6-Chlorophenanthridine (1 g), benzothiophene-2-boric acid (0.9 g), tetrakis(triphenylphosphine)palladium (0.32 g), potassium carbonate (3.2 g) were added to a 250 mL round-bottom flask, and water (30 mL) and 1,4-dioxane (90 mL) were added. The reaction mixture was protected by argon and the temperature of the reaction mixture was 100 °C for 16 h. After the reaction was completed, the mixture was cooled to room temperature, extracted with ethyl acetate and saturated brine, dried over anhydrous sodium sulfate, filtered, and the solvent was removed by vacuum distillation to obtain a crude product, which was purified by column chromatography with the eluent being V (Petroleum ether): V (ethyl acetate) = 20:1, and a white solid was obtained as 6-benzothiophene-2-phenanthridine; 1,10-phenanthroline-5,6-dione (3.15 g, 15 mmol), aniline (1.675 g, 18 mmol), p-hydroxybenzaldehyde (1.952 g, 5 mmol) and ammonium acetate (11.69 g, 180 mmol) were added to a 250 mL round-bottom flask. After adding 105 mL of glacial acetic acid, the reaction solution was protected by argon and the temperature was 118 °C. The reaction was carried out for 12 h. After the reaction was completed, it was cooled to room temperature and poured into water (200 mL). It was treated with 25% NH3 solution to pH = 6 to produce a thick dark green suspension. The dark green crude product was obtained by filtration and purified by column chromatography. The eluent was V (Dichloromethane):V (methanol) = 40:1, a white solid was obtained as 4-(1-phenyl-1) H -imidazole[4,5- f [1,10]phenanthren-2-yl)phenol; Add iridium trichloride trihydrate (0.5 g) and 6-benzothiophene-2-phenanthridine (0.88 g) into a 100 mL round-bottom flask, add 2-ethoxyethanol (30 mL) and water (10 mL), argon atmosphere, reaction liquid temperature 120 ℃, react for 24 h, wait for the reaction to completely cool to room temperature, slowly pour the reaction liquid into a beaker containing 100 mL of water, stir for 30 minutes, filter, dry the residue, and obtain a red solid as a dimer; Dimer (0.5 g), 4-(1-phenyl-1) H -imidazole[4,5- f [1,10]phenanthrene-2-yl)phenol (0.28 g) was added to a 100 mL round-bottom flask, and 2-ethoxyethanol (40 mL) was added. The reaction was carried out at 120 °C for 24 h under argon atmosphere. After the reaction was completed, potassium hexafluorophosphate (0.21 g) was added and stirred at normal pressure for 0.5 h. The reaction solution was extracted with ethyl acetate and water, dried over anhydrous sodium sulfate, filtered, and the solvent was removed by vacuum distillation to obtain a crude product, which was purified by column chromatography with the eluent being V (Dichloromethane): V (methanol) = 20:1, the red solid obtained is the ionic iridium complex Ir-4; 1 H NMR (400 MHz, DMSO- d 6) δ9.93 (s, 1H), 9.43 (dd, J = 17.6, 8.1 Hz, 2H), 9.11 (d, J = 5.2 Hz, 1H), 9.05 (d, J = 8.2 Hz, 1H), 8.95 (d, J = 6.3 Hz, 1H), 8.83 (t, J = 9.3 Hz, 2H), 8.48 (dd, J =14.7, 8.1 Hz, 2H), 8.26 – 8.03 (m, 10H), 7.74 (dd, J = 8.6, 5.4 Hz, 1H), 7.69 –7.50 (m, 7H), 7.43 (d, J= 8.6 Hz, 1H), 7.37 – 7.18 (m, 11H), 6.85 – 6.61 (m, 12H). Test 1: In phosphate buffer solution (pH=7.4), 9,10-anthracenediyl-bis(methylene)dicarboxylic acid was used as 1 O2 indicator, using terpyridine ruthenium as the standard, to evaluate the ionic iridium complexes Ir-1, Ir-2, Ir-3, and Ir-4 under 525 nm laser 1 O2 quantum yield, the specific experimental steps are as follows: Preparation of 9,10-Anthracenediyl-bis(methylene)dicarboxylic acid (1x10 -4 ) and containing ionic iridium complex Ir-2 (1x10 -5 ) mixed solution, and then irradiated with 525 nm laser (50 mW·cm -2 ) irradiation, the maximum absorbance was measured every 30 s at 380 nm, and the degradation effect of ionic iridium complexes Ir-1, Ir-2, Ir-3, and Ir-4 on 9,10-anthracenediyl-bis(methylene)dicarboxylic acid under laser was evaluated. The singlet oxygen yields of ionic iridium complexes Ir-1, Ir-2, Ir-3, and Ir-4 were calculated to be 26%, 37%, 45%, and 59%, respectively. Figure 5 As shown, it shows that it has excellent active oxygen generation ability.

[0016] Test 2: The CCK-8 method was used to detect the phototoxicity of ionic iridium complexes Ir-1, Ir-2, Ir-3, and Ir-4 to 4T1 cancer cells under laser and non-laser conditions. The specific experimental steps are as follows: 4T1 cancer cells were inoculated into well plates, and culture medium containing different concentrations of ionic iridium complexes Ir-1, Ir-2, Ir-3, and Ir-4 was added. After incubation with ionic iridium complexes Ir-1, Ir-2, Ir-3, and Ir-4 for 16 h, the cells were illuminated with a 525 nm laser (50 mW·cm -2 ) irradiated cells, while the control group was not irradiated. After incubation for 24 h, CCK-8 was added and incubated for 30 min. The absorbance of the absorption peak at 450 nm in each well was tested by an ELISA instrument to calculate the survival rate of cancer cells.

[0017] The results of CCK-8 test are as follows Figure 6 As shown, at 525 nm laser (50 mW·cm -2) under the action conditions, as the concentration of ionic iridium complexes Ir-1, Ir-2, Ir-3, and Ir-4 continued to increase, the cell survival rate continued to decrease, indicating that the ionic iridium complexes Ir-1, Ir-2, Ir-3, and Ir-4 of the present invention have excellent phototoxicity.

[0018] Test 3: The photodynamic therapy effect of ionic iridium complex Ir-3 was evaluated by mouse breast cancer. A total of 25 mice were randomly divided into 5 groups. The grouping and specific experimental steps are as follows: (1) No treatment; (2) Injection of saline and laser irradiation; (3) Injection of ionic iridium complex Ir-3 (4 μM) without laser treatment; (4) Injection of ionic iridium complex Ir-3 (4 μM) and laser treatment; (5) Injection of commercial photosensitizer Ce6 and laser treatment; After 13 days of treatment, all mice were killed and tumors and major organ tissues were collected to evaluate the therapeutic effect. The tumor inhibition coefficient was calculated as follows: Figure 7 As shown, the tumors in groups 1, 2, and 3 all grew rapidly, while the tumor growth in groups 4 and 5 was significantly inhibited. In addition, compared with the commercial photosensitizer Ce6, the ionic iridium complex Ir-3 of the present invention has a more excellent photodynamic therapy effect.

[0019] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. An ionic iridium complex photosensitizer, characterized in that: There are four types of photosensitizers, named Ir-1, Ir-2, Ir-3, and Ir-4, respectively, and their chemical structures are as follows: 。 2. The method for preparing the ionic iridium complex photosensitizer according to claim 1, characterized in that: The following steps are involved: (1) The precursor, benzothiophene-2-boric acid and catalyst were dissolved in a solvent in a molar ratio of 1:(1-1.2):(0.04-0.08), and the reaction system was kept oxygen-free. Suzuki coupling reaction was carried out at 100 °C in an alkaline environment for 16 h. (2) A mixture of 1,10-phenanthroline-5,6-dione, aniline, p-hydroxybenzaldehyde and ammonium acetate in a molar ratio of 1:(1-1.2):1:12 was dissolved in glacial acetic acid. The reaction system was kept oxygen-free and refluxed at 118 °C overnight. The reaction mixture was cooled to room temperature and the pH was adjusted to 6 to produce a thick dark green suspension. 4-(1-phenyl-1) H -imidazole[4,5- f [1,10]phenanthren-2-yl)phenol; (3) dissolving the reaction product obtained in step (1) and iridium trichloride trihydrate in a solvent at a molar ratio of 1:(0.4-0.6), keeping the reaction system oxygen-free, reacting at 120° C. for 24 h to obtain the corresponding dimer; (4) The dimer is mixed with 4-(1-phenyl-1) H -imidazole[4,5- f [1,10]phenanthrene-2-yl)phenol is dissolved in a mixed solvent at a molar ratio of 1:(2.3~2.8), the reaction system is kept oxygen-free, and a coordination reaction occurs at 120°C. After reacting for 24 hours, potassium hexafluorophosphate is added at a molar ratio of (3.5~4):1 to the dimer and reacted for 0.5 hours to obtain the target ionic iridium complex photosensitizer.

3. The method for preparing the ionic iridium complex photosensitizer according to claim 2, characterized in that: When preparing Ir-1, the precursor is 2-chloropyridine, and the reaction product of step (1) is 2-(2-pyridyl)benzothiophene; When preparing Ir-2, the precursor is 1-chloroisoquinoline, and the reaction product of step (1) is 1-benzothiophene-2-ylisoquinoline; When preparing Ir-3, the precursor is 2-chloroquinoline, and the reaction product of step (1) is 2-(1-benzothiophen-2-yl)quinoline; When preparing Ir-4, the precursor is 6-chlorophenanthridine, and the reaction product of step (1) is 6-benzothiophene-2-phenanthridine.

4. The method for preparing the ionic iridium complex photosensitizer according to claim 2 or 3, characterized in that: The solvent in step (1) is a mixture of water and 1,4-dioxane in a volume ratio of 1:3, and the amount ratio of the precursor to water is 1 g:30 mL.

5. The method for preparing the ionic iridium complex photosensitizer according to claim 2 or 3, characterized in that: The base used in the alkaline environment in step (1) is potassium carbonate, and the molar ratio of the precursor to potassium carbonate is 1:(5-5.2).

6. The method for preparing the ionic iridium complex photosensitizer according to claim 2, characterized in that: The ratio of 1,10-phenanthroline-5,6-dione to glacial acetic acid used in step (2) is 1 g:35 mL.

7. The method for preparing the ionic iridium complex photosensitizer according to claim 2 or 6, characterized in that: The pH was adjusted using 25% ammonia water.

8. The method for preparing the ionic iridium complex photosensitizer according to claim 2, characterized in that: The reaction solvent in step (3) is a mixture of water and 2-ethoxyethanol in a volume ratio of 1:3; the amount ratio of iridium trichloride trihydrate to water is 1 g:20 mL.

9. The method for preparing the ionic iridium complex photosensitizer according to claim 2, characterized in that: The solvent in step (4) is 2-ethoxyethanol; the ratio of the dimer to 2-ethoxyethanol is 1 g:80 mL.

10. The ionic iridium complex photosensitizer according to claim 1 can be used for the preparation of tumor photodynamic therapy drugs.

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