A binuclear ruthenium photocatalyst for photocatalytic oxidation of amino acids and its application

Abstract

The present invention discloses a binuclear ruthenium photocatalyst for photocatalytic oxidation of amino acids and its application. A binuclear ruthenium photocatalyst, whose structural formula is shown in formula (I): #imgabs0# The binuclear ruthenium photocatalyst has the ability to efficiently photocatalytically oxidize amino acids, and significantly improves its type I photocatalytic oxidation activity after combining with human serum albumin. At the same time, the complex has a strong photocatalytic effect on human non-small cell lung cancer cisplatin-resistant cell lines. Under light conditions (near infrared light), it has a strong growth and proliferation inhibition ability (IC 50 The phototoxicity of the prepared metallo-photocatalyst was 0.07 μM, while in the dark, its cytotoxicity was >100 μM, and its phototherapy index PI was as high as 1428, which is of great significance for the study of metallo-drugs for anti-drug-resistant tumors. It is expected to be used to prepare near-infrared excited anti-tumor photocatalytic drugs or drugs for anti-proliferation of cisplatin-resistant strains of human non-small cell lung cancer, and even anti-tumor metal photosensitizers.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical chemistry, and specifically relates to a binuclear ruthenium photocatalyst for photocatalytic oxidation of amino acids and application thereof. Background Art

[0002] Amino acids are the origin of life, the basic units of proteins, and a class of organic compounds with amino and carboxyl groups in their molecules. As an important component of living organisms, amino acids are extremely important substances for the nutrition, survival and development of living organisms, and play an important role in the regulation of material metabolism and information transmission in living organisms. At present, there are more than 50,000 known specific proteins in the human body, which are composed of 24 basic amino acids. The simplicity or complexity of proteins is determined by the number, variety and order of the amino acid combination and structural chain. In a protein molecule, the number of amino acids can be several or as many as hundreds or thousands, connected by peptide bonds into various forms, including chains, helices, spheres and branched structures. Amino acids play an important metabolic function. They are not only components of proteins, but also intermediate metabolites in various biosynthetic pathways. Changes in amino acid metabolism have a significant impact on tumor cells and tumor immune microenvironment.

[0003] Human serum albumin (HSA) is the earliest blood product extracted from human plasma and obtained for large-scale production and application. It is also the most abundant protein in human plasma, accounting for about 60% of the total plasma protein. HSA is synthesized by hepatocytes. Its molecular structure is a single-chain polypeptide containing 585 amino acid residues, with a molecular weight of 66438. The molecule contains 17 pairs of disulfide bonds and 1 free thiol group, and is not glycosylated. In clinical practice, HSA is mainly used as a drug for the following indications: 1. Shock caused by blood loss, trauma, and burns; 2. Maintenance treatment of patients with advanced cancer; 3. Increased intracranial pressure caused by cerebral edema and injury; 4. Edema or ascites caused by cancer, cirrhosis, and kidney disease. In the field of biomedicine, HSA can not only be used as a drug for direct intravenous injection, but also as an excellent drug carrier to prolong the half-life of the drug in vivo and achieve long-term drug effect. It can also be used as a stabilizer for biological preparations such as vaccines. Human serum albumin contains free thiol groups, has good water solubility, and has the characteristics of high biocompatibility, non-immunogenicity, and biodegradability. The strategy of bonding metal photocatalysts to proteins helps to improve the biocompatibility of metal photocatalysts.

[0004] Photocatalytic therapy is a non- / minimally invasive cancer treatment method. It is a relatively mild method that can irradiate light to a specific lesion area with little damage to healthy tissue. Photocatalytic therapy is also easier to design for the specific needs of patients, thus meeting the requirements of precision medicine. Photocatalytic therapy is mainly based on the type I photoinduced electron transfer mechanism, which can improve the photocatalytic therapeutic activity of hypoxic tumors. Metal photocatalysts are currently widely studied in the field of photocatalytic therapy. In order to improve the clinical practicality of their treatment, it is necessary to solve the shortcomings of the low near-infrared light absorption efficiency of the metal photocatalysts developed in the early stage, the low tumor-specific recognition ability, the single photocatalytic reaction substrate, and the unclear regulation mechanism of photocatalytic therapy for solid tumors. Summary of the invention

[0005] In order to overcome the above-mentioned deficiencies of the prior art, the present invention proposes a binuclear ruthenium photocatalyst, which has the function of photocatalytically oxidizing amino acids.

[0006] Another object of the present invention is to provide a method for preparing the above binuclear ruthenium photocatalyst.

[0007] Another object of the present invention is to provide an application of the above binuclear ruthenium photocatalyst.

[0008] In order to achieve the above object, the technical solution adopted by the present invention is:

[0009] The first aspect of the present invention provides a binuclear ruthenium photocatalyst, the structural formula of which is shown in formula (I):

[0010]

[0011] Formula (I).

[0012] The second aspect of the present invention provides a method for preparing the above binuclear ruthenium photocatalyst, comprising the following steps:

[0013] (1) reacting 4'-bromo-2,2':6',2"-terpyridine with ruthenium (III) chloride hydrate to generate a precursor compound Ru(tpy-Br)Cl3;

[0014] (2) the precursor compound Ru(tpy-Br)Cl3 described in step (1) reacts with 2,6-di(quinolin-8-yl)pyridine and is replaced with ammonium hexafluorophosphate ions to generate a ruthenium complex [Ru(bnp)(tpy-Br)](PF6)2;

[0015] (3) The ruthenium complex [Ru(bnp)(tpy-Br)](PF6)2 described in step (2) reacts with 2,5-di(2-ethylhexyl)-3,6-di(5-(trimethyltin)thiophene-2-yl)pyrrolo[3,4-c]pyrrole-1,4-(2H,5H)-dione to obtain the binuclear ruthenium photocatalyst.

[0016] Preferably, the step (1) is specifically as follows: 4'-bromo-2,2':6',2"-terpyridine and ruthenium (III) chloride hydrate are dissolved in an alcohol solution, refluxed at 75-95°C for 8-16h, and cooled.

[0017] Further preferably, the step (1) is specifically as follows: 4'-bromo-2,2':6',2"-terpyridine and ruthenium (III) chloride hydrate are dissolved in an alcohol solution, refluxed at 80-90°C for 10-14h, and cooled; in some specific preferred embodiments of the present invention, 4'-bromo-2,2':6',2"-terpyridine and ruthenium (III) chloride hydrate are dissolved in an alcohol solution, refluxed at 85°C for 12h; the alcohol solution in step (1) includes an ethanol solution.

[0018] Preferably, in step (1), the molar ratio of 4'-bromo-2,2':6',2"-terpyridine to ruthenium (III) chloride hydrate is 1:(1-1.2).

[0019] Preferably, the step (2) is specifically as follows: the precursor compounds Ru(tpy-Br)Cl3 and 2,6-di(quinolin-8-yl)pyridine are dissolved in an alcohol solution, refluxed at 180-220°C for 3-6h, cooled, and then ammonium hexafluorophosphate is added for ion replacement.

[0020] Further preferably, the step (2) is specifically as follows: the precursor compounds Ru(tpy-Br)Cl3 and 2,6-di(quinolin-8-yl)pyridine are dissolved in an alcohol solution, refluxed at 190-210°C for 3-5h, cooled, and then ammonium hexafluorophosphate is added for ion replacement; in some specific preferred embodiments of the present invention, the precursor compounds Ru(tpy-Br)Cl3 and 2,6-di(quinolin-8-yl)pyridine are dissolved in an alcohol solution, refluxed at 200°C for 4h, cooled, and then ammonium hexafluorophosphate is added for ion replacement; the alcohol solution in step (2) includes an ethylene glycol solution.

[0021] Preferably, in the step (2), after adding ammonium fluorophosphate ions for replacement, filtering, washing and drying are performed to obtain a ruthenium complex [Ru(bnp)(tpy-Br)](PF6)2.

[0022] Preferably, in step (2), the molar ratio of the precursor compound Ru(tpy-Br)Cl3 to 2,6-di(quinolin-8-yl)pyridine is 1:(0.8-1.2).

[0023] Preferably, the step (3) is specifically as follows: under a protective atmosphere, the ruthenium complex [Ru(bnp)(tpy-Br)](PF6)2, 2,5-di(2-ethylhexyl)-3,6-di(5-(trimethyltin)thiophene-2-yl)pyrrolo[3,4-c]pyrrole-1,4-(2H,5H)-dione and the catalyst are dissolved in a solvent, stirred at 100-135°C for 18-24h, cooled, filtered, washed and dried to obtain the binuclear ruthenium photocatalyst.

[0024] Further preferably, the step (3) is specifically as follows: under a protective atmosphere, the ruthenium complex [Ru(bnp)(tpy-Br)](PF6)2, 2,5-di(2-ethylhexyl)-3,6-di(5-(trimethyltin)thiophen-2-yl)pyrrolo[3,4-c]pyrrole-1,4-(2H,5H)-dione, and the catalyst are dissolved in a mixture of toluene and N,N-dimethylformamide, stirred at 110-120°C for 18-22h, cooled, filtered, and washed. , dried to obtain the binuclear ruthenium photocatalyst; in some specific preferred embodiments of the present invention, the ruthenium complex [Ru(bnp)(tpy-Br)](PF6)2, 2,5-di(2-ethylhexyl)-3,6-di(5-(trimethyltin)thiophene-2-yl)pyrrolo[3,4-c]pyrrole-1,4-(2H,5H)-dione, and the catalyst are dissolved in a mixture of toluene and N,N-dimethylformamide (volume ratio 1:1) and stirred at 115°C for 20 hours.

[0025] Preferably, in the step (3), the molar ratio of [Ru(bnp)(tpy-Br)](PF6)2,2,5-di(2-ethylhexyl)-3,6-di(5-(trimethyltin)thiophene-2-yl)pyrrolo[3,4-c]pyrrole-1,4-(2H,5H)-dione is 1:(1.8-2.2); further preferably, in the step (3), the molar ratio of [Ru(bnp)(tpy-Br)](PF6)2,2,5-di(2-ethylhexyl)-3,6-di(5-(trimethyltin)thiophene-2-yl)pyrrolo[3,4-c]pyrrole-1,4-(2H,5H)-dione is 1:(1.9-2.1).

[0026] In some specific embodiments of the present invention, in step (3), a catalyst is added during the reaction, and the catalyst includes tetrakis(triphenylphosphine)palladium.

[0027] The third aspect of the present invention provides the use of the binuclear ruthenium photocatalyst in the preparation of near-infrared light-excited anti-tumor drugs and / or drugs for preventing the proliferation of cisplatin-resistant strains of human non-small cell lung cancer.

[0028] Preferably, the near-infrared light-excited anti-tumor drug is a near-infrared light-excited anti-human lung cancer drug.

[0029] The fourth aspect of the present invention provides a near-infrared light-excited anti-tumor drug, the active ingredient of which includes the binuclear ruthenium photocatalyst.

[0030] The fifth aspect of the present invention provides a drug for preventing the proliferation of cisplatin-resistant strains of human non-small cell lung cancer, wherein the active ingredient of the drug for preventing the proliferation of cisplatin-resistant strains of human non-small cell lung cancer includes the binuclear ruthenium photocatalyst.

[0031] The sixth aspect of the present invention provides an anti-tumor metal photosensitizer, the active ingredient of which includes the binuclear ruthenium photocatalyst.

[0032] Compared with the prior art, the present invention has the following beneficial effects:

[0033] The present invention discloses a novel near-infrared light-excited binuclear ruthenium photocatalyst, which has the ability of highly efficient photocatalytic oxidation of amino acids, and significantly improves its type I photocatalytic oxidation activity after being combined with human serum albumin. At the same time, the complex has a strong photocatalytic effect on human non-small cell lung cancer cisplatin-resistant cell lines. Under light conditions (near-infrared light), it has a strong growth and proliferation inhibition ability (IC 50 The phototoxicity of the prepared metallo-photocatalyst was 0.07 μM, while in the dark, its cytotoxicity was >100 μM, and its phototherapy index PI was as high as 1428, which is of great significance for the study of metallo-drugs for anti-drug-resistant tumors. It is expected to be used to prepare near-infrared excited anti-tumor photocatalytic drugs or drugs for anti-proliferation of cisplatin-resistant strains of human non-small cell lung cancer, and even anti-tumor metal photosensitizers. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 is the chemical structural formula of the binuclear ruthenium photocatalyst of the embodiment;

[0035] Figure 2 The UV absorption spectrum of the near-infrared excited binuclear ruthenium photocatalyst;

[0036] Figure 3 The ability of near-infrared excited binuclear ruthenium photocatalyst to combine with human serum albumin to photocatalytically produce superoxide anions;

[0037] Figure 4 The ability of near-infrared excited binuclear ruthenium photocatalyst to combine with human serum albumin to photocatalytically produce hydrogen peroxide;

[0038] Figure 5 The ability of near-infrared excited binuclear ruthenium photocatalyst to photocatalytically oxidize twenty amino acids to produce hydrogen peroxide;

[0039] Figure 6 Near-infrared excited binuclear ruthenium photocatalyst is used to combat the dark toxicity and phototoxicity of cisplatin-resistant human non-small cell lung cancer cell line (A549 / DDP). DETAILED DESCRIPTION

[0040] The specific embodiments of the present invention are further described below. It should be noted that the description of these embodiments is used to help understand the present invention, but does not constitute a limitation of the present invention. In addition, the technical features involved in each embodiment of the present invention described below can be combined with each other as long as they do not conflict with each other.

[0041] The experimental methods in the following examples are conventional methods unless otherwise specified, and the experimental materials used in the following examples are commercially available unless otherwise specified.

[0042] Example 1

[0043] The structural formula of the binuclear ruthenium photocatalyst of this embodiment is as follows Figure 1 As shown, the synthesis method comprises the following steps:

[0044] (1) Ru(tpy-Br)Cl3 is generated by the reaction of 4'-bromo-2,2':6',2"-terpyridine with ruthenium(III) chloride hydrate.

[0045] 4'-Bromo-2,2':6',2"-terpyridine (312 mg, 1 mmol) and ruthenium (III) chloride hydrate (225 mg, 1.1 mmol) were dissolved in 20 mL of ethanol solution, refluxed at 85 °C for 12 h and then cooled to room temperature. The reaction solution was filtered, and the filter cake was washed with ethanol and n-hexane and then vacuum dried to obtain a brown solid powder Ru(tpy-Br)Cl3.

[0046] The chemical reaction equation above is as follows:

[0047]

[0048] (2) Ru(tpy-Br)Cl3 reacts with 2,6-di(quinolin-8-yl)pyridine to generate [Ru(dqp)(tpy-Br)](PF6)2

[0049] The precursor Ru(tpy-Br)Cl3 (260 mg, 0.5 mmol) and 2,6-di(quinolin-8-yl)pyridine (167 mg, 0.5 mmol) (CAS: 102576-05-6) were dissolved in 20 mL of ethylene glycol solution, stirred at 200 °C for 4 h, cooled to room temperature, added with saturated NH4PF6 aqueous solution, stirred at room temperature for 1 h, filtered, and the filter cake was washed with water and ethanol. After vacuum drying, the ruthenium complex [Ru(bnp)(tpy-Br)](PF6)2 purple powder was obtained.

[0050] The chemical reaction equation above is as follows:

[0051]

[0052] (3) Reaction of [Ru(bnp)(tpy-Br)](PF6)2 and 2,5-di(2-ethylhexyl)-3,6-di(5-(trimethyltin)thiophen-2-yl)pyrrolo[3,4-c]pyrrole-1,4-(2H,5H)-dione to form a binuclear ruthenium photocatalyst

[0053] [Ru(bnp)(tpy-Br)](PF6)2(109mg, 0.1mmol), 2,5-di(2-ethylhexyl)-3,6-di(5-(trimethyltin)thiophen-2-yl)pyrrolo[3,4-c]pyrrole-1,4-(2H,5H)-dione(43mg, 0.05mmol) and tetrakis(triphenylphosphine)palladium(6mg, 0.005mmol) were dissolved in 12mL of toluene / N,N-dimethylformamide (V / V=1:1) and stirred at 115°C for 20h under argon protection. After the reaction was completed, the mixture was cooled to room temperature, saturated brine was added, the precipitate was collected by filtration, washed with water and toluene, and dried in vacuo to obtain a blue solid powder.

[0054] The chemical reaction equation above is as follows:

[0055]

[0056] The mass spectrum of the product is: ESI-MS [CH3OH, m / z]: 465 [M-4PF6 - ] 4+ ;

[0057] The H NMR spectrum of the product is: 1H NMR (500MHz, DMSO-d6) δ9.52(d,J=8.3Hz,3H),9.45(s,2H),9.14(d,J=8.7Hz,2H),9.08(d,J=3.9Hz,1H),8.89( d,J=8.1Hz,2H),8.84–8.70(m,5H),8.45(d,J=8.1Hz,2H),8.31(d,J=4.3Hz,2H),7.89(t,J=7.9Hz,2H),7.73–7. 64(m,3H),7.56(dd,J=8.2,4.3Hz,2H),7.42(d,J=5.7Hz,2H),7.12(t,J=6.7Hz,2H),4.34–4.15(m,6H),3.50(s, 6H), 1.64 (p, J = 6.8Hz, 4H), 1.48–1.19 (m, 21H), 1.02–0.96 (m, 4H), 0.90 (t, J = 7.5Hz, 7H), 0.83 (t, J = 7.3Hz, 5H).

[0058] Experimental Example 2

[0059] Performance test of binuclear ruthenium photocatalyst obtained in Example 1

[0060] 1. Absorption spectrum measurement of near-infrared binuclear ruthenium photocatalyst

[0061] The binuclear ruthenium photocatalyst of Example 1 was prepared into a 10 μM sample solution using anhydrous ethanol (C2H5OH) and PBS as solvents, and then the ultraviolet absorption spectrum of the binuclear ruthenium photocatalyst was recorded using a double-beam ultraviolet-visible spectrophotometer. Figure 2 The absorbance of the compound in ethanol and PBS was characterized, indicating that it has good light absorption ability in organic solvents and water solvents.

[0062] 2. Photocatalytic production of superoxide anions by near-infrared binuclear ruthenium photocatalyst combined with human serum albumin

[0063] In order to detect the ability of the binuclear ruthenium photocatalyst synthesized in Example 1 to combine with human serum albumin to photocatalytically generate superoxide anions, dihydrorhodamine 123 (abbreviated as DHR 123) was used to measure the ability of the binuclear ruthenium photocatalyst to generate superoxide anions. When superoxide anions are generated in the solution, DHR 123 will immediately capture the superoxide anions in the solution, and DHR 123 is oxidized to generate the fluorescent derivative rhodamine 123, so that bright green fluorescence (Ex / Em=500 / 536nm) is emitted, wherein the increase in fluorescence intensity can indicate that superoxide anions are generated in the solution. Thus, the change in the fluorescence spectrum of the sample to be tested and the mixed solution of DHR123 under different illumination times can reflect the ability to generate superoxide anions.

[0064] An aqueous solution containing binuclear ruthenium photocatalyst (5 μM), human serum albumin HSA (5 μM), and DHR 123 reagent (10 μM) and an aqueous solution containing binuclear ruthenium photocatalyst (5 μM) and DHR 123 reagent (10 μM) were placed in two cuvettes, and their superoxide anion generation capacity was measured under 700 nm light conditions. Figure 3 As shown, Figure 3 The left picture shows an aqueous solution without human serum albumin HSA, and the right picture shows an aqueous solution containing human serum albumin HSA. Figure 3 It can be seen that the binuclear ruthenium photocatalyst combined with human serum albumin significantly improves its ability to produce superoxide anions after red light excitation.

[0065] 3. Determination of the ability of near-infrared excited binuclear ruthenium photocatalyst to combine with human serum albumin to produce hydrogen peroxide

[0066] In order to detect the ability of the binuclear ruthenium photocatalyst synthesized in Example 1 to combine with human serum albumin to generate hydrogen peroxide by photocatalysis, the OxiVision Green hydrogen peroxide (H2O2) detection probe was used to detect the ability of the binuclear ruthenium photocatalyst to combine with human serum albumin to generate hydrogen peroxide. The OxiVision Green hydrogen peroxide probe has no fluorescence and no absorption in the visible light region. H2O2 will cause a rapid increase in fluorescence, accompanied by an increase in the visible wavelength absorption band. Thus, the ability to produce hydrogen peroxide can be reflected by detecting the fluorescence plate of the enzyme-linked immunosorbent assay instrument EX490 / EM525.

[0067] 1 μL binuclear ruthenium photocatalyst (10 nM), 50 μL human serum albumin (HAS) (1 nM) and 50 μL OxiVisionGreen hydrogen peroxide (H2O2) detection probe working solution were added to a 96-well plate. In addition, 1 μL binuclear ruthenium photocatalyst (10 nM), 50 μL PBS and 50 μL OxiVision Green hydrogen peroxide (H2O2) detection probe working solution were added to a 96-well plate to measure their hydrogen peroxide generation capacity under 700 nm illumination. Figure 4 As shown, the binuclear ruthenium photocatalyst combined with human serum albumin has a significant ability to produce hydrogen peroxide after light irradiation.

[0068] 4. Determination of the ability of near-infrared excited binuclear ruthenium photocatalyst to produce hydrogen peroxide by photocatalytic oxidation of twenty amino acids

[0069] In order to detect the ability of the binuclear ruthenium photocatalyst synthesized in Example 1 to combine with human serum albumin to generate hydrogen peroxide by photocatalysis, the OxiVision Green hydrogen peroxide (H2O2) detection probe was used to detect the ability of the binuclear ruthenium photocatalyst to combine with human serum albumin to generate hydrogen peroxide. The OxiVision Green hydrogen peroxide probe has no fluorescence and no absorption in the visible light region. H2O2 will cause a rapid increase in fluorescence, accompanied by an increase in the visible wavelength absorption band. Thus, the ability to produce hydrogen peroxide can be reflected by detecting the fluorescence plate of the enzyme-linked immunosorbent assay instrument EX490 / EM525.

[0070] 50 μL of glycine (Gly), alanine (Ala), valine (Val), leucine (Leu), isoleucine (Ile), methionine (Met), proline (Pro), tryptophan (Trp), serine (Ser), tyrosine (Tyr), cysteine ​​(Cys), phenylalanine (Phe), asparagine (Asn), glutamine (Gln), threonine (Thr), aspartic acid (Asp), glutamic acid (Glu), lysine (Lys), arginine (Arg) and histidine (His) (10 mg / mL) and 1 μL of binuclear ruthenium photocatalyst (10 nM), 50 μL of OxiVision Green hydrogen peroxide (H2O2) detection probe working solution were added to a 96-well plate, and the hydrogen peroxide generation capacity was measured under 700 nm light conditions. Figure 5 As shown, the binuclear ruthenium photocatalyst has the ability to selectively photocatalyze twenty kinds of amino acids to produce hydrogen peroxide after light irradiation.

[0071] 5. Photodynamic therapy effect of binuclear ruthenium photocatalyst on cisplatin-resistant human non-small cell lung cancer cell lines

[0072] Resazurin solution is blue and is usually used as an acid-base indicator (orange at pH 3.8 to dark purple at pH 6.5) and a redox indicator. When performing cell activity tests, resazurin can penetrate into cells and be irreversibly reduced to pink by living cells, while red fluorescent resorufin appears. The absorbance or fluorescence intensity of resorufin is positively correlated with the number of cells and the reducing ability, so the cell proliferation can be analyzed by an enzyme-linked immunofluorescence detector.

[0073] The steps of the Resazurin experiment are as follows:

[0074] (1) First, revive one tube of A549 / DDP tumor cells and culture them with fresh complete culture medium (DMEM medium + 10% fetal bovine serum + 1% penicillin-streptomycin mixture). After two passages, start the experiment.

[0075] (2) When the cells reached the logarithmic growth phase, they were seeded into two 96-well plates at a density of 5,000 cells / well (100 μL of culture medium was used to culture cells in each well, one plate was for the light control group and the other was for the dark control group), and cultured in a 37°C, 5% CO2 incubator.

[0076] (3) After the cells adhere to the wall, the original culture medium was aspirated and 100 μL of binuclear ruthenium photocatalyst at seven concentrations of 100, 50, 10, 1, 0.1, 0.01, and 0.001 mM was added to each well, the cells were gently shaken and incubated in a carbon dioxide incubator (37°C, 5% CO2) in the dark.

[0077] (4) After incubation for 8 h, the cell culture plates in the illumination group were placed under a 700 nm light source for 30 min (light dose of 71 J / cm 2 ), and then returned to the incubator for incubation in the dark for 40 h (the cells in the dark control group were kept in the incubator incubated in the dark).

[0078] (5) After incubation for 40 h, the culture medium was discarded from each well, and 80 μL of resazurin (100 mg / mL) was added to each well. The cells were incubated in a 37°C incubator for another 4 h. EX540 / EM590 was detected using the fluorescence plate of an enzyme-linked immunosorbent assay (ELISA) to calculate the cell proliferation inhibition rate and obtain the IC 50 value (drug concentration when the inhibition rate is equal to 50%).

[0079] Figure 6 The resazurin method was used to detect the killing effect of different concentrations of binuclear ruthenium photocatalysts on cisplatin-resistant human non-small cell lung cancer cell line (A549 / DDP cells) under dark and light treatment conditions (near infrared light). It can be seen from the figure that in the absence of light, the IC 50 >100μM, IC against cisplatin-resistant human non-small cell lung cancer cell lines under light conditions 50 The phototherapy index PI is as high as 1428, which indicates that the binuclear ruthenium photocatalyst of the present invention has a strong photodynamic therapy effect.

[0080] In summary, the binuclear ruthenium photocatalyst provided by the present invention has a strong photochemotherapy effect on human non-small cell lung cancer cisplatin-resistant cell line (A549 / DDP cells). Under light conditions (near infrared light), it has a strong ability to inhibit the growth and proliferation of human non-small cell lung cancer cisplatin-resistant cells (IC 50 0.07μM), while under dark conditions, its cytotoxicity is>100μM, and the phototherapy index PI is as high as 1428, which is of great significance for the study of metal drugs used for near-infrared excitation to fight drug-resistant tumors.

[0081] The embodiments of the present invention are described in detail above, but the present invention is not limited to the described embodiments. For those skilled in the art, various changes, modifications, substitutions and variations of these embodiments are made without departing from the principles and spirit of the present invention, and still fall within the protection scope of the present invention.

Claims

1. A binuclear ruthenium photocatalyst for photocatalytic oxidation of amino acids, characterized in that: Its structural formula is shown in formula (I):

2. A method for preparing the binuclear ruthenium photocatalyst according to claim 1, characterized in that: The following steps are involved: (1) reacting 4'-bromo-2,2':6',2"-terpyridine with ruthenium (III) chloride hydrate to generate a precursor compound Ru(tpy-Br)Cl3; (2) the precursor compound Ru(tpy-Br)Cl3 described in step (1) reacts with 2,6-di(1,8-naphthyridin-2-yl)pyridine, and is replaced with ammonium hexafluorophosphate ions to generate a ruthenium complex [Ru(bnp)(tpy-Br)](PF6)2; (3) The ruthenium complex [Ru(bnp)(tpy-Br)](PF6)2 described in step (2) reacts with 2,5-di(2-ethylhexyl)-3,6-di(5-(trimethyltin)thiophene-2-yl)pyrrolo[3,4-c]pyrrole-1,4-(2H,5H)-dione to obtain the binuclear ruthenium photocatalyst.

3. The method for preparing a binuclear ruthenium photocatalyst according to claim 2, characterized in that: The step (1) specifically comprises: dissolving 4'-bromo-2,2':6',2"-terpyridine and ruthenium (III) chloride hydrate in an alcohol solution, reacting under reflux at 75-95°C for 8-16h, and cooling.

4. The method for preparing a binuclear ruthenium photocatalyst according to claim 2, characterized in that: The step (2) is specifically as follows: the precursor compound Ru(tpy-Br)Cl3 and 2,6-di(1,8-naphthyridin-2-yl)pyridine are dissolved in an alcohol solution, refluxed at 180-220°C for 3-6 hours, cooled, and then ammonium hexafluorophosphate is added for ion replacement.

5. The method for preparing a binuclear ruthenium photocatalyst according to claim 2, characterized in that: The step (3) is specifically as follows: under a protective atmosphere, the ruthenium complex [Ru(bnp)(tpy-Br)](PF6)2, 2,5-di(2-ethylhexyl)-3,6-di(5-(trimethyltin)thiophene-2-yl)pyrrolo[3,4-c]pyrrole-1,4-(2H,5H)-dione and the catalyst are dissolved in a solvent, stirred at 100-135°C for 18-24h, cooled, filtered, washed and dried to obtain the binuclear ruthenium photocatalyst.

6. The method for preparing a binuclear ruthenium photocatalyst according to claim 5, characterized in that: The step (3) specifically comprises: under a protective atmosphere, dissolving the ruthenium complex [Ru(bnp)(tpy-Br)](PF6)2, 2,5-di(2-ethylhexyl)-3,6-di(5-(trimethyltin)thiophene-2-yl)pyrrolo[3,4-c]pyrrole-1,4-(2H,5H)-dione and the catalyst in a mixed solution of toluene and N,N-dimethylformamide, stirring at 110-120°C for 18-22h, cooling, filtering, washing and drying to obtain the binuclear ruthenium photocatalyst.

7. Use of the binuclear ruthenium photocatalyst according to claim 1 in the preparation of near-infrared light-excited anti-tumor drugs and / or drugs for preventing the proliferation of cisplatin-resistant strains of human non-small cell lung cancer.

8. A near-infrared light-excited anti-tumor drug, characterized in that: The active ingredient of the near-infrared light-excited anti-tumor drug includes the binuclear ruthenium photocatalyst described in claim 1.

9. A drug for inhibiting the proliferation of cisplatin-resistant strains of human non-small cell lung cancer, characterized in that: The active ingredient of the drug for resisting the proliferation of cisplatin-resistant strains of human non-small cell lung cancer includes the binuclear ruthenium photocatalyst according to claim 1.

10. An anti-tumor metal photosensitizer, characterized in that: The active ingredient of the anti-tumor metal photosensitizer includes the binuclear ruthenium photocatalyst according to claim 1.

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