CN113912651B - Cationic iridium complex and preparation method and application thereof - Google Patents
Cationic iridium complex and preparation method and application thereof Download PDFInfo
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- 125000002091 cationic group Chemical group 0.000 title claims abstract description 27
- 229910052741 iridium Inorganic materials 0.000 title claims abstract description 27
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 title claims abstract description 27
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 23
- -1 pyridine-2-yl Chemical group 0.000 claims description 22
- 238000000034 method Methods 0.000 claims description 21
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- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0033—Iridium compounds
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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Abstract
The invention relates to a cationic iridium complex and a preparation method and application thereof. The cationic iridium complex of the invention is prepared from [ (. eta.) ]5‑Me5C5）Ir（III）Cl]2（μ2‑Cl）2Is one of (η)5‑Me5C5) Ir (III) Cl structure substituted with 3 fPhtz. The invention combines in vitro and in vivo experiments to prove that the cationic iridium complex can reduce oxidative stress reaction after spinal cord injury by removing oxygen free radicals, thereby promoting the repair of the spinal cord injury and providing a new research direction and a new medicine source for the auxiliary treatment of the spinal cord injury medicine.
Description
Technical Field
The invention belongs to the technical field of biological medicines, and particularly relates to a cationic iridium complex and a preparation method and application thereof.
Background
Spinal Cord Injury (SCI) is a transient or permanent loss of motor, sensory, and autonomic nervous function below the level of injury, resulting from structural and functional changes in Spinal cord tissue caused by external forces. The pathophysiological processes are often divided into primary and secondary injuries. Among them, Oxidative Stress (OS) is one of the major mechanisms of secondary injury. OS is a state of imbalance between oxidation and antioxidation in vivo, and tends to oxidize, resulting in inflammatory infiltration of neutrophils, increased secretion of protease, and production of a number of oxidation intermediates.
Normally, the oxidation substance and antioxidant substance generated in the body are in equilibrium, and once the body is damaged, the oxidation substance generates too much, such as too much superoxide anion (.O)2-), hydroxyl radical (. OH) and hydrogen peroxide (H)2O2) And the like, which causes damage to the body. After SCI, a large amount of reactive oxygen species is produced, the redox balance is disrupted, and the spinal cord is further aggravated on the basis of primary injury. If the compound can effectively inhibit the generation of oxygen free radicals in the acute phase of SCI or eliminate the oxygen free radicals, the progress of injury can be effectively reduced.
Currently, iridium (III) complexes are of great interest due to their high emission efficiency, long excited state lifetime, optical and thermal stability, and easy tunability of emission wavelength. Therefore, the iridium (III) complex has wide application prospects in the aspects of chemical sensors, biological probes, photocatalytic water reduction, organic light-emitting diodes, light-emitting electrochemical cells and the like. In addition, various cationic iridium complexes have been reported, such as [ (. eta. ]) complex5-Cp*）Ir（C^N）Cl]PF61It has strong anticancer effect, and is mainly used as an oxidant to promote the generation of ROS so as to inhibit the proliferation of tumor cells. However, to date, no ir (iii) complex has been synthesized and reported to have antioxidant effects, and its application in spinal cord injury repair has not been studied.
Disclosure of Invention
The invention aims to solve the technical problems in the prior art, and provides a cationic iridium complex and a preparation method and application thereof. The cationic iridium complex can effectively remove oxygen free radicals, resist oxidative stress induced injury and promote spinal cord injury repair.
In order to solve the above technical problems, the present invention is achieved by the following technical solutions.
The first aspect of the present invention provides a cationic iridium complex, the structural formula of which is as follows:
Preferably, the cationic iridium complex is prepared by the following method:
(1) heating and melting 2-cyanopyridine, adding hydrazine monohydrate, adding ethanol, and stirring overnight; evaporating the solvent under reduced pressure, suspending the obtained solid in petroleum ether, cooling in an ice bath, filtering, recrystallizing with toluene, and purifying to obtain (pyridine-2-yl) amidehydrazone;
(2) putting the (pyridine-2-yl) amidehydrazone obtained in the step (1) into a Schlenk tube, adding sodium carbonate, heating at 35 +/-2 ℃ for 5 minutes, adding Dimethylacetamide (DMAA) and Tetrahydrofuran (THF), and cooling to 0 ℃ to obtain a mixture; adding the mixed solution of m-fluorobenzoyl chloride and dimethylacetamide into the mixture, stirring for 5 hours, turning off refrigeration, and returning to room temperature; filtering and washing after the reaction is finished, adding the obtained solid into ethylene glycol, heating to 190 ℃, reacting for 30 minutes, cooling and collecting white solid to obtain a 3FPHtz ligand;
(3) will [ (eta ]5-Cp*）IrCl2]2And 3FPHtz ligand to methylene Chloride (CH)2Cl2) Stirring under nitrogen for 16 hours, adding ammonium hexafluorophosphate, removing all solvent under reduced pressure to obtain a yellow solid, and reacting with CH2Cl2Saturated dissolving, and spreading n-hexane above the saturated solution for crystallization.
Preferably, the dosage ratio of the 2-cyanopyridine, the hydrazine monohydrate, the ethanol and the petroleum ether in the step (1) is 0.05 mol: 0.05 mol: 2.5 mL: 25 mL.
Preferably, the mixed solution of the (pyridine-2-yl) amide hydrazone, the sodium carbonate, the dimethylacetamide, the tetrahydrofuran, the m-fluorobenzoyl chloride and the dimethylacetamide in the step (2) is used in a ratio of 7.5 mmol: 7.5 mmol: 7.5 mL: 2.5 mL: 10 mL.
Preferably, the volume ratio of the m-fluorobenzoyl chloride to the dimethyl acetyl in the m-fluorobenzoyl chloride and dimethyl acetyl mixed solution in the step (2) is 3: 1.
Preferably, the [ (η) in step (3)5-Cp*）IrCl2]2The dosage ratio of the 3FPHtz ligand to the dichloromethane to the ammonium hexafluorophosphate is 0.2 mmol: 0.44 mmol: 15mL of: 0.8 mmol.
The second aspect of the present invention provides a method for preparing a cationic iridium complex, comprising the steps of:
(1) heating and melting 2-cyanopyridine, adding hydrazine monohydrate, adding ethanol, and stirring overnight; evaporating the solvent under reduced pressure, suspending the obtained solid in petroleum ether, cooling in an ice bath, filtering, recrystallizing with toluene, and purifying to obtain (pyridine-2-yl) amidehydrazone;
(2) putting the (pyridine-2-yl) amidehydrazone obtained in the step (1) into a Schlenk tube, adding sodium carbonate, heating at 35 +/-2 ℃ for 5 minutes, adding Dimethylacetamide (DMAA) and Tetrahydrofuran (THF), and cooling to 0 ℃ to obtain a mixture; adding the mixed solution of m-fluorobenzoyl chloride and dimethylacetamide into the mixture, stirring for 5 hours, turning off refrigeration, and returning to room temperature; filtering and washing after the reaction is finished, adding the obtained solid into ethylene glycol, heating to 190 ℃, reacting for 30 minutes, cooling and collecting white solid to obtain a 3FPHtz ligand;
(3) will [ (eta ]5-Cp*）IrCl2]2And 3FPHtz ligand to methylene Chloride (CH)2Cl2) Stirring under nitrogen for 16 hours, adding ammonium hexafluorophosphate, removing all solvent under reduced pressure to obtain a yellow solid, and reacting with CH2Cl2Saturated dissolving, and spreading n-hexane above the saturated solution for crystallization.
Preferably, the dosage ratio of the 2-cyanopyridine, the hydrazine monohydrate, the ethanol and the petroleum ether in the step (1) is 0.05 mol: 0.05 mol: 2.5 mL: 25 mL.
Preferably, the mixed solution of the (pyridine-2-yl) amide hydrazone, the sodium carbonate, the dimethylacetamide, the tetrahydrofuran, the m-fluorobenzoyl chloride and the dimethylacetamide in the step (2) is used in a ratio of 7.5 mmol: 7.5 mmol: 7.5 mL: 2.5 mL: 10 mL.
Preferably, the volume ratio of the m-fluorobenzoyl chloride to the dimethyl acetyl in the m-fluorobenzoyl chloride and dimethyl acetyl mixed solution in the step (2) is 3: 1.
Preferably, the [ (η) in step (3)5-Cp*）IrCl2]2The dosage ratio of the 3FPHtz ligand to the dichloromethane to the ammonium hexafluorophosphate is 0.2 mmol: 0.44 mmol: 15mL of: 0.8 mmol.
In a third aspect, the present invention provides a pharmaceutical composition for preventing and/or treating diseases associated with oxidative stress, comprising a cationic iridium complex having a structural formula as shown below:
preferably, the disease associated with oxidative stress includes, but is not limited to, secondary spinal cord injury.
In a fourth aspect, the invention provides the use of a cationic iridium complex in the manufacture of a medicament for the prevention and/or treatment of a disease associated with oxidative stress.
Preferably, the disease associated with oxidative stress includes, but is not limited to, secondary spinal cord injury.
Compared with the prior art, the invention has the following technical effects:
(1) the cationic iridium complex D79 provided by the invention can effectively scavenge oxygen free radicals. Treatment with D79 promoted branch formation and neurite outgrowth, indicating that D79 can repair hippocampal neuronal cells against oxidative stress-induced injury without significant toxicity to the cells or tissues.
(2) In vivo studies show that D79 can significantly enhance the behavioral functions of mice and reduce oxidative stress reactions after spinal cord injury, thereby promoting the repair of spinal cord injury and providing a new research idea and a new medicine source for the drug-assisted treatment of spinal cord injury.
Drawings
FIG. 1 is a schematic diagram of a synthetic process of 3FPHtz ligand
FIG. 2 shows 3FPHtz ligands1H NMR chart.
Fig. 3 is a schematic diagram of the synthesis process of D79.
FIG. 4 shows D791H NMR chart.
FIG. 5 is a graph showing the results of measuring the radical scavenging ability of D79; wherein, left: ABTS free radical scavenging method, right: DPPH radical scavenging method.
FIG. 6 is a graph showing the results of toxicity tests of D79 on hippocampal neurons.
Fig. 7 is a graph showing the results of the study of the effect of D79 on injured hippocampal neurons (# indicates comparison with Control group and # indicates comparison with Injury group).
FIG. 8 is a graph showing the results of a study of the behavioral effects of D79 on animals following spinal cord injury; wherein, left: motor function Score (BBB Score), right: gale combined Score (BMS Score).
FIG. 9 is a typical image of a mouse in vivo.
FIG. 10 is a graph showing fluorescence intensity of in vivo imaging of mice.
Detailed Description
In order to make the objects, technical solutions and effects of the present invention clearer and clearer, the present invention is further described in detail below with reference to examples. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
Among the reagents used in the context of the present invention, those commercially available are not specifically mentioned. For animal experiments, the related procedures and methods meet the requirements of medical ethics. The experimental methods used in the present invention are all conventional methods and techniques in the art.
Representative results from selection of biological experimental replicates are presented in the context figure, and data are presented as mean ± SD and mean ± SEM as specified in the figure. All experiments were repeated at least three times. Data were analyzed using GraphPad Prism 5.0 or SPSS 22.0 software. And comparing the difference of the average values of two or more groups by adopting conventional medical statistical methods such as t test, chi-square test, variance analysis and the like. p < 0.05 was considered a significant difference.
Example 1 preparation and characterization of cationic Iridium Complex (D79)
A method for preparing a cationic iridium complex, comprising the steps of:
(1) synthesis of (pyridin-2-yl) amide hydrazone: 2-Cyanopyridine (5.2 g, 0.05 mol) was slowly heated to melt, then hydrazine monohydrate (2.6 mL, 2.7g, 0.05 mol) was added to give a cloudy mixture. Adding ethanol (2.5 mL), stirring overnight to form a gel product, evaporating the solvent under reduced pressure, suspending in petroleum ether (25 mL), cooling in an ice bath, filtering, and recrystallizing with toluene to purify to obtain (pyridin-2-yl) amidehydrazone (5.3 g, 77.4%);
(2) synthesis of 3FPHtz ligand: (pyridin-2-yl) amidehydrazone (1.0 g, 7.5 mmol) was taken and placed in a flame dried, nitrogen purged 50mL Schlenk tube, sodium carbonate (0.8 g, 7.5 mmol) was added, heated at 35 + -2 deg.C for 5 minutes, 7.5mL of dried Dimethylacetamide (DMAA) and 2.5mL of dried Tetrahydrofuran (THF) were added, and then cooled to 0 deg.C to give a light yellow suspension. A new 50mL dry Schlenk flask was charged with 7.5mmol of m-fluorobenzoyl chloride and 2.5mL of DMAA and the solution was added dropwise to the pre-cooled mixture of amidoazones to give a bright yellow solution. The bright yellow solution was stirred for 5 hours and the refrigeration was turned off to bring it back to room temperature. After the reaction was completed, a pale yellow solid was obtained by filtration, and washed with water and ethanol. Adding the obtained solid into 10mL of glycol, heating to 190 ℃, reacting for 30 minutes, cooling to form a white solid, namely the 3FPHtz ligand, collecting, and using without further purification.
Synthesis process of 3FPHtz ligand and1the H NMR chart is shown in FIG. 1-2.
(3) Synthesizing a cationic iridium complex: adding 0.2mmol of [ (. eta.) ]5-Cp*）IrCl2]2And 0.44mmol of 3FPHtz ligand in 15mL CH2Cl2Then, the mixture was stirred under nitrogen for 16 hours, and 0.143g (0.88 mmol) of ammonium hexafluorophosphate was added thereto. After completion of the reaction, all solvents were removed under reduced pressure to obtain a yellow solid with CH2Cl2Saturated dissolution and n-hexane spreading above the saturated dissolution for crystallization to obtain the cationic iridium complex (D79).
Synthesis process of cationic iridium complex D79 and application thereof1The H NMR chart is shown in FIGS. 3 to 4.
Example 2 study of scavenging ability of D79 for oxygen free radicals
The method for measuring the scavenging capacity of the D79 free radical by adopting the ABTS method and the DPPH method comprises the following specific steps:
(1) reacting ABTS stock solution (5 mmol/L, dissolved in PBS) with manganese oxide solution to form ABTS free radicals (ABTS. +);
(2) mixing different concentrations of D79 with the ABTS free radical solution in the step (1);
(3) the absorbance at 734 nm was measured over 120 minutes using a cell imaging multimode reader (rotation 5, BioTek Instruments Inc.).
The results of the detection are shown in FIG. 5. The results show that D79 obviously inhibits the formation of ABTS free radicals and is time-dependent and dose-dependent, and the D79 has high activity of scavenging ROS, so that the compound can be used as an effective free radical scavenger to prevent the ROS from damaging neurons.
Further, an in vitro free radical scavenging test of DPPH (1, 1-diphenyl-2-picrylhydrazyl) was carried out in the same manner, and the results were the same as those of ABTS test.
Example 3 toxicity study of D79 on neuronal cells
(1) Collecting Sprague-Dawley (SD) rat brain hippocampus tissue, adding 0.25% pancreatin, and digesting at 37 deg.C for 15 min;
(2) after the trypsin action is stopped by bovine serum albumin, the tissue is cleaned and lightly ground;
(3) the isolated hippocampal neurons were seeded at 20000 cells/mL in 35 mm dishes (Costar, Cambridge, MA) in DMEM medium (containing glutamine, Gibco, Carlsbad, CA, Cat # 12430054) containing 10% fetal bovine serum, 10% nutrient mixture F-12 at 37 deg.C and 95% O2、5% CO2The culture box is used for culturing for 24 hours;
(4) replacing the original culture medium with Neurobasal medium containing 5% B-27 (Gibco), and standing at 37 deg.C and 95% O2、5% CO2Culture ofCulturing in a culture box for 24 h;
(5) after the cells are adhered, D79 with different concentrations is added into each hole respectively, and then the incubation is carried out for 24 hours;
(6) the viability of hippocampal neurons in culture was assessed using the CCK8 kit (Abnova (Walnut, CA)).
The results are shown in FIG. 6. The results show that the studied concentrations of D79 all showed no significant difference in cell viability compared to the blank control group, and the cell viability rate was over 80%, even at a high concentration of 25.0 μmol/L, the cell viability rate was close to 90%, indicating that the D79 treatment had no significant cytotoxicity to neuronal cells.
Example 4 study of the repair Effect of D79 on neurons
(1) Collecting Sprague-Dawley (SD) rat brain hippocampus tissue, adding 0.25% pancreatin, and digesting at 37 deg.C for 15 min;
(2) after the trypsin action is stopped by bovine serum albumin, the tissue is cleaned and lightly ground;
(3) adding the obtained hippocampal neurons into a culture medium containing 120 mu M glutamic acid, and incubating for 12 hours to form an injury model of the hippocampal neurons;
(4) the effect on neurons was observed by adding different concentrations of D79.
Results as shown in fig. 7, the effect of complex D79 on neurite outgrowth was assessed by quantifying the length and total number of branch neurites. The results show that D79 branches significantly more at 6.25. mu. mol/L than in the lesion group; it was also found that the number of one and two branches after D79 treatment was much higher than in the lesion group and increased with increasing concentration. The length of the dendrites is similar to the number of dendrites. The total branch length at 6.25 μmol/L for D79 was significantly higher than for the other groups, while D79 at 1.56 μmol/L was also associated with increased neuron length relative to the injured group. The length of the primary branch and the secondary branch of the D79 at 6.25 mu mol/L is also obviously improved compared with the damage group.
Example 5 in vivo functional study of D79
(1) Selecting 24 female mice with the age of 6 weeks, dividing the mice into four groups, wherein each group comprises 6 mice, including a blank Control group (Control group, 6 mice), a sham treatment Control group (sham group, 6 mice) (only vertebral plates are removed and the spinal cord is not damaged), a model group (Injury group, 6 mice), and a D79 group (Injury + D79 group, 6 mice) (carrying out intraperitoneal injection on D7910 mu L with the concentration of 6 mu g/mu L1 time a day after the spinal cord Injury on the second day), and constructing a mouse model of the spinal cord Injury according to the following method:
a. removing hair on the back of the mouse to expose the skin on the back of the mouse;
b. anesthesia: 1.25% tribromoethanol is used for intraperitoneal injection anesthesia at the dose of 200 mug/20 g, the anesthesia is successful due to stable respiration, the muscle strength of limbs is obviously weakened, and the pain reflex and the corneal reflex disappear;
c. exposing the spinal cord: wiping with iodophor cotton ball for 2 times to sterilize skin; levels of thoracic vertebrae in segments 9-11 (T9-T11) were determined and a longitudinal incision 2.5cm long was made in the center of the back at T9-T11. The paraspinal muscles were dissected blunt, the spinous processes and laminae were removed with rongeurs to expose the T9-T11 segment of the spinal cord completely, taking care to avoid additional tissue damage during the procedure. Then, the spinal cord is spread and fixed by a fixer so as to fully expose the spinal cord;
d. fixing the mouse on a Louisville Injury System device (LISA), adjusting the spinal cord to be below the impactor, monitoring the laser beam by the impactor to confirm the impact position, and determining the spinal cord Injury degree by the impact depth, wherein the impact depth is 0.6mm in the embodiment;
e. the incision was closed and gentamicin 2000U was subcutaneously injected after surgery 1 time a day for 3 consecutive days with 1 artificial bladder emptying every 8 h.
(2) Monitoring: the BBB score and BMS score were performed every 3 days, starting on the sixth day after injury, with the mine trials performed at weeks 3 and 4. The results are shown in FIG. 8. The results show that, initially, hind limb locomotion was completely lost in all SCI mice. The D79 treatment group showed behavioral function shear recovery indices 6-30 days after injury, followed by gradual improvement in BBB and BMS scores over time. 30 days after injury, the BBB and BMS scores of the mice in the D79 treatment group are obviously higher than those of the mice in the injury group, and the difference has statistical significance.
(3) Live imaging of small animals: live small animal imaging was performed on day 3 and day 7 post-injury. First, 0.1ml/20g L-012 (chemiluminescence (CHL) probe) was injected intraperitoneally, and the concentration of L-012 was 4 mg/ml. And 5 minutes later, carrying out intraperitoneal injection anesthesia by using 1.25% tribromoethanol at a dose of 200 microgram/20 g, and carrying out living body imaging on the small animals after the anesthesia succeeds.
The results are shown in FIGS. 9-10. The results show that there is little bioluminescence of ROS in the spinal cord of normal mice, while the bioluminescence intensity of ROS in the spinal cord of spinal cord injured mice is significantly increased and increases with time. The bioluminescence intensity of ROS was significantly reduced after 7D treatment with D79, and did not change much over time, further confirming that D79 has significant oxygen free radical scavenging and spinal cord injury repair effects in vivo.
In combination, D79 is effective in scavenging oxygen free radicals. Treatment with D79 promoted branch formation and neurite outgrowth, indicating that D79 can repair hippocampal neuronal cells against oxidative stress-induced injury. In addition, in vivo studies showed that D79 treatment significantly enhanced behavioral function in mice. Meanwhile, video analysis of the behavior of mice in the group treated with D79 revealed that the total distance traveled, the average of the distances to the point area, the distance to the point, and the frequency of movement were significantly higher than those in the injury group, similar to those in the normal group and the sham group. The results show that D79 treatment effectively improved mouse function and behavior, and the quantitative value of ROS bioluminescence intensity indicates that intravenous injection of D79 can promote the repair of spinal cord injury.
The above detailed description section specifically describes the analysis method according to the present invention. It should be noted that the above description is only for the purpose of helping those skilled in the art better understand the method and idea of the present invention, and not for the limitation of the related contents. The present invention may be appropriately adjusted or modified by those skilled in the art without departing from the principle of the present invention, and the adjustment and modification also fall within the scope of the present invention.
Claims (10)
1. A cationic iridium complex, wherein the cationic iridium complex has a structural formula as follows:
2. a preparation method of a cationic iridium complex is characterized by comprising the following steps:
(1) heating and melting 2-cyanopyridine, adding hydrazine monohydrate, adding ethanol, and stirring overnight; evaporating the solvent under reduced pressure, suspending the obtained solid in petroleum ether, cooling in an ice bath, filtering, recrystallizing with toluene, and purifying to obtain (pyridine-2-yl) amidehydrazone;
(2) putting the (pyridine-2-yl) amidehydrazone obtained in the step (1) into a Schlenk tube, adding sodium carbonate, heating at 35 +/-2 ℃ for 5 minutes, adding dimethylacetamide and tetrahydrofuran, and cooling to 0 ℃ to obtain a mixture; adding the mixed solution of m-fluorobenzoyl chloride and dimethylacetamide into the mixture, stirring for 5 hours, turning off refrigeration, and returning to room temperature; filtering and washing after the reaction is finished, adding the obtained solid into ethylene glycol, heating to 190 ℃, reacting for 30 minutes, cooling and collecting white solid to obtain a 3FPHtz ligand; the 3FPHtz ligand structure is shown as follows:
(3) will [ (eta ]5-Cp*）IrCl2]2And 3FPHtz ligand to methylene Chloride (CH)2Cl2) Stirring under nitrogen for 16 hours, adding ammonium hexafluorophosphate, removing all solvent under reduced pressure to obtain a yellow solid, and reacting with CH2Cl2Saturated dissolving, and spreading n-hexane above the saturated solution for crystallization.
3. The method according to claim 2, wherein the 2-cyanopyridine, the hydrazine monohydrate, the ethanol and the petroleum ether are used in a ratio of 0.05 mol: 0.05 mol: 2.5 mL: 25 mL.
4. The method according to claim 2, wherein the mixed solution of (pyridin-2-yl) amidehydrazone, sodium carbonate, dimethylacetamide, tetrahydrofuran, m-fluorobenzoyl chloride and dimethylacetamide in the step (2) is used in a ratio of 7.5 mmol: 7.5 mmol: 7.5 mL: 2.5 mL: 10 mL.
5. The preparation method according to claim 2, wherein the volume ratio of the m-fluorobenzoyl chloride to the dimethylacetamide in the m-fluorobenzoyl chloride and dimethylacetamide mixed solution in the step (2) is 3: 1.
6. The method according to claim 2, wherein the [ (η) in the step (3)5-Cp*）IrCl2]2The dosage ratio of the 3FPHtz ligand to the dichloromethane to the ammonium hexafluorophosphate is 0.2 mmol: 0.44 mmol: 15mL of: 0.88 mmol.
7. A pharmaceutical composition for preventing and/or treating diseases associated with oxidative stress, comprising the cationic iridium complex according to claim 1 or the cationic iridium complex produced by the production method according to any one of claims 2 to 6 as an active ingredient.
8. The pharmaceutical composition according to claim 7, wherein the disease associated with oxidative stress is secondary spinal cord injury.
9. Use of the cationic iridium complex according to claim 1 or the cationic iridium complex prepared by the preparation method according to any one of claims 2 to 6 for the preparation of a medicament for the prevention and/or treatment of diseases associated with oxidative stress.
10. The use according to claim 9, wherein the disease associated with oxidative stress is secondary spinal cord injury.
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| Ángela Vivancos et al..Unveiling the role of ancillary ligands in acceptorless benzyl alcohol dehydrogenation and etherification mediated by mesoionic carbene iridium complexes.《Dalton Trans.》.2017, * |
| Half-Sandwich Ir(III) and Os(II) Complexes of Pyridyl-Mesoionic Carbenes as Potential Anticancer Agents;Juran Kralj et al.;《Organometallics》;20191009;4082-4092页 * |
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