Phenanthroline functionalized nitrogen heterocyclic carbene homonuclear and heteronuclear silver-gold compounds and methods and applications

Abstract

The present invention discloses phenanthroline-functionalized nitrogen heterocyclic carbene homonuclear and heteronuclear silver-gold compounds, methods, and applications. A binuclear N-heterocyclic carbene (NHC) silver complex (NHC-Ag2) and a heteronuclear NHC silver / gold bimetallic complex (NHC-Ag / Au) are synthesized using a phenanthroline-functionalized imidazole salt (HLPF6) ligand. NHC ligands have strong coordination ability and are easy to modify structurally, making them suitable for structural optimization of metal drugs. Heterocyclic functionalized NHC ligands are easy to construct multinuclear metal compounds, which can enhance the drug activity of metal drugs against cancer cells. The synthesized nitrogen heterocyclic carbene binuclear silver and heteronuclear silver / gold compounds have good in vitro anticancer activity in different cancer cell lines. Mechanism studies in colon cancer LoVo cells show that they cause increased intracellular reactive oxygen species and mitochondrial dysfunction, inducing cell necrosis.

Description

Technical Field

[0001] The present invention belongs to the field of metal organic complexes, and specifically relates to phenanthroline-functionalized nitrogen heterocyclic carbene homonuclear and heteronuclear silver-gold compounds, methods and applications. Background Art

[0002] Platinum-based metallodrugs are an important class of chemotherapeutic agents widely used in the clinical treatment of cancer. However, platinum-based metallodrugs have inherent limitations, such as dose toxicity, low selectivity, and the susceptibility of tumor cells to drug resistance. These drawbacks have stimulated the exploration of non-platinum-based anti-tumor metallodrugs. In addition to platinum-based metallodrugs, silver and gold compounds are also important metallodrugs. Historically, these compounds have been primarily used to treat infections, burns, and surgical instruments. While most research has focused on platinum and ruthenium compounds in the exploration of anticancer metallodrugs, the application of silver and gold compounds has also garnered attention. Unlike platinum-based metallodrugs, which primarily act on nucleic acids, silver and gold compounds often exert their biological activity through other modes of action. On the cell membrane, silver and gold ions can remove electrons from the cell membrane, disrupting its integrity and permeability. Within the cell, silver and gold ions can depolarize the mitochondrial membrane potential and induce excessive production of reactive oxygen species (ROS), leading to mitochondrial dysfunction and cell death. Furthermore, in practice, resistance of cancer cells to silver and gold compounds has rarely been observed. In view of the above advantages, silver and gold compounds should have important research value in cancer treatment.

[0003] In light of these factors, we have specifically developed homonuclear and heteronuclear silver-gold compounds, methods, and applications of phenanthroline-functionalized nitrogen heterocyclic carbene (NHC) ligands. A binuclear silver compound (NHC-Ag2) and a heteronuclear silver / gold compound (NHC-Ag / Au) were synthesized using phenanthroline-functionalized nitrogen heterocyclic carbene (NHC) ligands. NHC ligands have strong coordination capabilities and are easily modified, making them suitable for structural optimization of metallodrugs. Heterocyclic-functionalized NHC ligands facilitate the construction of polynuclear metallodrug compounds, which can enhance the pharmacological activity of metallodrugs against cancer cells. Summary of the Invention

[0004] The present invention aims to provide phenanthroline-functionalized nitrogen heterocyclic carbene homonuclear and heteronuclear silver-gold compounds and methods and applications to solve the problems raised in the above-mentioned background technology.

[0005] The object of the present invention is achieved by the following technical scheme: phenanthroline functionalized nitrogen heterocyclic carbene homonuclear and heteronuclear silver-gold compounds, including phenanthroline functionalized nitrogen heterocyclic carbene ligands, are used to synthesize a binuclear silver NHC-Ag2 and a heteronuclear silver / gold compound NHC-Ag / Au respectively;

[0006] The specific reaction equation is as follows:

[0007]

[0008] A method for preparing homonuclear and heteronuclear silver-gold compounds of nitrogen heterocyclic carbene functionalized with phenanthroline, specifically comprising the following steps:

[0009] The first step is the preparation of phenanthroline functionalized imidazolium salt ligand HLPF6;

[0010] The second step is the preparation of binuclear nitrogen heterocyclic carbene silver compound NHC-Ag2;

[0011] The third step is the preparation of heteronuclear nitrogen heterocyclic carbene silver / gold compound NHC-Ag / Au.

[0012] Furthermore, in the first step, the phenanthroline functionalized imidazolium salt ligand HLPF6 was prepared;

[0013] The specific steps include:

[0014] 1,10-phenanthroline-2-imidazole and benzyl chloride were dissolved in acetonitrile and heated to reflux. After the reaction, the mixture was cooled and the acetonitrile solvent was removed. Deionized water was added to fully dissolve the solid matter in the reaction flask. The mixture was filtered and the filtrate was collected. A saturated aqueous solution of ammonium hexafluorophosphate was added dropwise to the filtrate to immediately precipitate a large amount of white solid. The solid compound was collected by suction filtration, washed three times with deionized water, and then dried to obtain a white phenanthroline-functionalized imidazole salt ligand HLPF6.

[0015] Furthermore, in the second step, a binuclear nitrogen heterocyclic carbene silver compound NHC-Ag2 was prepared;

[0016] The method specifically comprises the following steps: functionalizing an imidazole salt ligand HLPF6 with a phenanthroline functional group, mixing silver oxide in acetonitrile, heating, reacting in the dark, filtering the solution through a short silica gel column after the black silver oxide powder has substantially disappeared, collecting the clarified filtrate, transferring the filtrate to a test tube, and slowly volatilizing and recrystallizing the ether to obtain a binuclear nitrogen heterocyclic carbene silver compound.

[0017] Furthermore, the third step, the preparation of the heteronuclear nitrogen heterocyclic carbene silver / gold compound NHC-Ag / Au, specifically includes the following steps: phenanthroline functionalized imidazole salt ligand HLPF6, silver oxide is mixed in acetonitrile, heated, and after the reaction in the dark, (Et2S)AuCl is added and stirring is continued at room temperature. After the reaction is completed, the solution is centrifuged, filtered through a short silica gel column, and the clear filtrate is collected. The filtrate is transferred to a test tube and recrystallized through ether to obtain the heteronuclear nitrogen heterocyclic carbene silver / gold copper compound NHC-Ag / Au.

[0018] Furthermore, the two central Ag(I) ions of the NHC-Ag2 cation are coordinated to the two functionalized nitrogen heterocyclic carbene ligands in different ways.

[0019] Furthermore, the Ag(I) ion is coordinated to the C atoms of the two carbene ligands in a linear manner, with a C-Ag-C bond angle of 172.5° and Ag-C bond lengths of 2.092 and The Ag2 ion is coordinated to the four N atoms of the two phenanthroline atoms in a tetrahedral configuration, and the Ag-N bond lengths are 2.219, 2.260, 2.438 and

[0020] Furthermore, the cation of NHC-Ag / Au contains two phenanthroline-functionalized nitrogen heterocyclic carbene ligands, an Ag(I) ion and an Au(I) ion. In NHC-Ag / Au, the Ag(I) ion is coordinated to the four N atoms of the four phenanthrolines in a distorted tetrahedral configuration, and the Au(I) is coordinated to the two carbene C atoms in a linear manner. The C-Au-C bond angle is 176.2°, and the Au-C bond lengths are 2.007 and 2.007, respectively.

[0021] The invention discloses an application of phenanthroline-functionalized nitrogen heterocyclic carbene homonuclear and heteronuclear silver-gold compounds, which is characterized in that the phenanthroline-functionalized nitrogen heterocyclic carbene homonuclear and heteronuclear silver-gold compounds are applied to the research on treating platinum-resistant cancer.

[0022] Furthermore, NHC-Ag2 and NHC-Ag / Au caused excessive production of reactive oxygen species in cells by destroying the mitochondrial membrane potential, thereby causing cell necrosis. Compared with platinum drugs, silver and gold complexes have different modes of action in cancer cells.

[0023] Compared with the prior art, the present invention has the following beneficial effects:

[0024] The present invention synthesizes a binuclear silver (NHC-Ag2) and a heteronuclear silver / gold compound (NHC-Ag / Au) respectively through phenanthroline-functionalized nitrogen heterocyclic carbene (NHC) ligands. NHC ligands have strong coordination ability and are easy to modify structurally, making them suitable for structural optimization of metal drugs. Heterocyclic functionalized NHC ligands can easily construct polynuclear metal compounds, which can enhance the drug activity of metal drugs against cancer cells. In in vitro cell experiments, the synthesized nitrogen heterocyclic carbene binuclear silver and heteronuclear silver / gold compounds have good in vitro anticancer activity in different cancer cell lines. Mechanism studies in colon cancer LoVo cells show that NHC-Ag2 and NHC-Ag / Au mainly act on the mitochondria of cells, causing an increase in intracellular reactive oxygen species and mitochondrial dysfunction, inducing cell necrosis. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 Schematic diagram of 50% probability ellipsoid crystal of complex NHC-Ag2;

[0026] Figure 2Schematic diagram of 50% probability ellipsoidal crystal of the complex NHC-Ag / Au;

[0027] Figure 3 Fluorescence microscopy images and schematic diagrams of changes in mitochondrial membrane potential: (a) Fluorescence microscopy image of LoVo cells stained with JC-1; (b) Flow cytometry analysis showing changes in mitochondrial membrane potential of LoVo cells;

[0028] Figure 4 Schematic diagram of flow cytometric analysis showing the production of reactive oxygen species (ROS) in LoVo cells;

[0029] Figure 5 Schematic diagram of apoptosis and necrosis of LoVo cells determined by Annexin V / PI double staining after incubation with NHC-Ag2 and NHC-Ag / Au (4 μM) for 24 h. DETAILED DESCRIPTION

[0030] The technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0031] like Figure 1-5 As shown, phenanthroline functionalized nitrogen heterocyclic carbene homonuclear and heteronuclear silver-gold compounds, including phenanthroline functionalized nitrogen heterocyclic carbene ligands, were used to synthesize a binuclear silver NHC-Ag2 and a heteronuclear silver / gold compound NHC-Ag / Au respectively;

[0032] The specific reaction equation is as follows:

[0033] Specific embodiment one:

[0035] A method for preparing homonuclear and heteronuclear silver-gold compounds of nitrogen heterocyclic carbene functionalized with phenanthroline, specifically comprising the following steps:

[0036] Preparation of phenanthroline functionalized imidazolium salt ligand (HLPF6);

[0037] 1,10-phenanthroline-2-imidazole (492 mg, 2.0 mmol) and benzyl chloride (252 mg, 2.0 mmol) were dissolved in 30 mL of acetonitrile and heated to reflux. After 6 h of reaction, the mixture was cooled, the acetonitrile solvent was removed, 50 mL of deionized water was added to fully dissolve the solid matter in the reaction flask, filtered, and the filtrate was collected. Saturated aqueous ammonium hexafluorophosphate solution was added dropwise to the filtrate, and a large amount of white solid was immediately precipitated. The solid compound was collected by suction filtration, washed three times with deionized water, and dried to obtain 832 mg of white phenanthroline functionalized imidazole salt ligand (HLPF6), with a yield of 86.3%. Theoretical value of elemental analysis (C 22 H 17 N4PF6, %): C, 54.78; H, 3.55; N, 11.62; Found (%): C, 53.90; H, 3.51; N, 11.60. 1 H NMR (400MHz, DMSO-d6): δ9.92 (s, 1H), 9.09 (d, J = 4Hz, 1H), 8.67 (d, J = 8Hz, 1H), 8.43 (d, J = 8Hz, 1H), 8.34 ( s, 1H), 8.02-7.96 (m, 3H), 7.78-7.75 (dd, J=8, 4Hz, 1H), 7.65 (s, 1H), 7.52-7.46 (m, 5H), 5.52 (s, CH2, 2H). 13 CNMR (101MHz, DMSO-d6): δ148.88,146.09,141.86,141.54,140.97,136.38,134.86,130.21,12 9.58,129.49,129.46,129.31,129.05,128.04,127.57,125.29,124.23,120.70,115.59,53.29.

[0038] Preparation of binuclear nitrogen heterocyclic carbene silver compound (NHC-Ag2);

[0039] Phenanthroline functionalized imidazole salt ligand HLPF6 (241 mg, 0.5 mmol) and silver oxide (60 mg, 0.25 mmol) were mixed in 15 mL of acetonitrile, heated to 50°C, and reacted in the dark for 6 hours. After the black silver oxide powder had essentially disappeared, the solution was filtered through a short silica gel column, and the clear filtrate was collected. The filtrate was transferred to a test tube and recrystallized by slow evaporation of ether to obtain 203 mg of a binuclear nitrogen heterocyclic carbene silver compound (NHC-Ag2) with a yield of 69.0%. Elemental analysis theoretical value (C 44 H 32 Ag2 12N8P2, %): C, 44.85; H, 2.74; N, 9.51; found: C, 45.11; H, 2.65; N, 9.40. 1 H NMR (400MHz, DMSO-d6): δ9.16 (d, J=8Hz, 2H), 8.77 (d, J=8Hz, 2H), 8.51-8.3 2(m, 10H), 7.87-7.80(m, 4H), 6.69-6.62(m, 6H), 6.37(s, 4H), 5.14(s, 4H). 13 C NMR (101MHz, DMSO-d6): δ181.54 (Ag-C), 151.77, 149.90, 142.51, 141.94, 141.30, 139.47, 136.21, 130.24, 129.44, 128.18, 128.04, 127.85, 127.72, 127.40, 125.41, 124.69, 123.01, 120.46, 55.20.

[0040] Preparation of heteronuclear nitrogen heterocyclic carbene silver / gold compounds (NHC-Ag / Au);

[0041] Phenanthroline functionalized imidazolium salt ligand HLPF6 (241 mg, 0.5 mmol) and silver oxide (60 mg, 0.25 mmol) were mixed in 15 mL of acetonitrile and heated to 50°C. After 6 hours of reaction in the dark, (Et2S)AuCl (89 mg, 0.25 mmol) was added and stirred at room temperature for 2 hours. After the reaction, the solution was centrifuged and filtered through a short silica gel column to collect the clear filtrate. The filtrate was transferred to a test tube and recrystallized from diethyl ether to obtain 193 mg of heteronuclear nitrogen heterocyclic carbene silver / gold copper compound (NHC-Ag / Au) with a yield of 60.1%. The theoretical value of elemental analysis (C 44 H 32 FWf 12 N8P2, %): C, 41.69; H, 2.54; N, 8.84; found: C, 41.11; H, 2.59; N, 8.90. 1 HNMR (400MHz, DMSO-d6): δ9.17 (d, J=8Hz, 2H), 8.81 (d, J=8Hz, 2H), 8.67 (d, J=4Hz, 2H), 8.49-8.43 (m, 6H), 8.39-8.36 (m, 2H), 7.97 (s, 2H), 7.86 (q, J = 4Hz, 2H), 6.65 (d, J = 8Hz, 4H), 6.51 (t, J = 8Hz, 2H), 6.16 (t, J = 8Hz, 4H), 5.28 (d, J = 48Hz, 4H). 13C NMR (101MHz, DMSO-d6): 182.03 (Au-C), 152.17, 149.25, 142.58, 141.98, 141.22, 139.53, 136. 09, 130.46, 129.71, 128.42, 127.65, 127.51, 127.19, 125.53, 124.75, 123.51, 120.70, 55.33.

[0042] The phenanthroline functionalized imidazole salt HLPF6 was prepared by reacting 1,10-o-phenanthroline-2-imidazole with benzyl chloride and then anion exchange. In acetonitrile solvent, HLPF6 was reacted with Ag2O to obtain a binuclear nitrogen heterocyclic carbene silver compound NHC-Ag2. After the reaction of HLPF6 with Ag2O, an equivalent amount of (Et2S)AuCl was added, and the heteronuclear nitrogen heterocyclic carbene silver / gold compound NHC-Ag / Au was obtained after metal exchange. HLPF6, NHC-Ag2, and NHC-Ag / Au were characterized by nuclear magnetic resonance and elemental analysis, respectively. 1 In H NMR, the acidic characteristic peak of imidazolium salt C-2 appeared at 9.92ppm, indicating that the imidazolium salt has been successfully synthesized. The proton signals of phenanthroline ring, imidazole ring and benzyl group appeared in the range of 9.09-7.46ppm, which is consistent with the molecular structure of HLPF6. 1 In the H NMR spectrum, the hydrogen proton signal at the C2 position of imidazole disappears, indicating that the imidazole salt forms a carbene ligand after deprotonation and coordinates with the metal. In addition, the resonance signals of the imidazole ring, phenanthroline ring and benzyl group are similar to those of the carbene ligand precursor imidazole salt HLPF6. 13 In the C NMR spectrum, the resonance signals of carbene Ag-C and Au-C appeared at δ181 ppm and δ182 ppm, respectively, which are similar to those of previously reported NHC-silver and NHC-gold compounds.

[0043] The structures of NHC-Ag2 and NHC-Ag / Au were further characterized by X-ray single crystal diffraction. Figure 1 As shown, the two central Ag(I) ions are coordinated to the two functionalized nitrogen heterocyclic carbene ligands in different ways. The Ag1 ion is coordinated to the C atoms of the two carbene ligands in a linear manner, with a C-Ag-C bond angle of 172.5° and Ag-C bond lengths of 2.092 and 2.093°, respectively. The Ag2 ion is coordinated to the four N atoms of the two phenanthroline atoms in a tetrahedral configuration, and the Ag-N bond lengths are 2.219, 2.260, 2.438 and The cationic structure of NHC-Ag / Au is as follows Figure 2 As shown, the molecule contains two phenanthroline functionalized nitrogen heterocyclic carbene ligands, an Ag(I) ion and an Au(I) ion. Similar to NHC-Ag2, in NHC-Ag / Au, the Ag(I) ion is coordinated to the four N atoms of the four phenanthroline in a distorted tetrahedral configuration, and the Au(I) is coordinated to the two carbene C atoms in a linear manner. The C-Au-C bond angle is 176.2°, and the Au-C bond lengths are 2.007 and 2.007, respectively. In addition, the bond lengths of Ag-Ag and Ag-Au in NHC-Ag2 and NHC-Ag / Au are 2.8287 and 2.8607 respectively. This indicates that weak metal-metal interactions exist in both metal complexes.

[0044] Table 1 below shows the in vitro cytotoxicity test, which shows the IC50 (μM) values ​​of NHC-Ag2, NHC-Ag / Au, cis-Pt and HLPF6 against four cancer cells after 48 h of incubation.

[0045] Table.1IC50(μM)values ​​of NHC-Ag2,NHC-Ag / Au,cis-Pt and HLPF6 against four types of cancer cell line after 48h of drug exposure.

[0046]

[0047]

[0048] The anticancer activities of NHC-Ag2, NHC-Ag / Au, and the imidazole salt HLPF6 were evaluated using the MTT assay in LoVo, HeLa, A2780, and A549 cancer cells, using the clinically used cisplatin as a reference. As shown in Table 1, the imidazole salt HLPF6 exhibited only minimal anticancer activity against these four cancer cell lines, with IC50 values ​​exceeding 45 μM. Compared to HLPF6, the corresponding NHC-Ag2 and NHC-Ag / Au compounds exhibited comparable or superior anticancer activity to cisplatin in all tested cell lines. For example, in LoVo colon cancer cells, the IC50 values ​​of NHC-Ag2 and NHC-Ag / Au were 5.6±0.3 μM and 6.4±0.4 μM, respectively, which were lower than the IC50 value of cisplatin of 7.7±0.4 μM. This indicates that the coordination of silver and gold ions significantly enhances the cytotoxicity of the complexes, demonstrating anticancer activity comparable to that of cisplatin. At the same time, the strong coordination ability of nitrogen heterocyclic carbene ligands can improve the stability of silver and gold ions in complex physiological environments, thereby exerting their pharmacological effects.

[0049] After being taken up by cancer cells, the cationic portion of the complex usually interacts with the negatively charged mitochondria, depolarizing the mitochondrial membrane potential and thus destroying mitochondrial function. To confirm this process, the mitochondrial membrane potential indicator JC-1 was used to study the changes in mitochondrial membrane potential of LoVo cells before and after the treatment of NHC-Ag2 and NHC-Ag / Au. Figure 3 As shown in a, after JC-1 labeling, the mitochondrial matrix of normal LoVo cells appears as orange fluorescent aggregates; after incubation with NHC-Ag2 and NHC-Ag / Au (4μM) for 12 hours, LoVo cells show green fluorescence and orange fluorescence decreases. This shows that NHC-Ag2 and NHC-Ag / Au have destroyed the mitochondrial membrane potential of LoVo cells, and JC-1 dye cannot accumulate in the mitochondrial matrix, thereby emitting green fluorescence. Flow cytometric analysis and verification showed that after incubation with NHC-Ag2 and NHC-Ag / Au (4μM) for 12 hours, the green fluorescence ratio of LoVo cells increased from 3.24% to 36.9% and 40.2%, respectively ( Figure 3 b).

[0050] Mitochondria are the main site of cellular aerobic respiration. When mitochondrial function is damaged, electrons will leak from the mitochondrial respiratory chain and produce excessive reactive oxidative species (ROS) in the cell. The reactive oxygen species indicator DCFH-DA can usually be used to assess the production of ROS in cells. After DCFH-DA is hydrolyzed in the cell, it is oxidized in the presence of ROS to produce green fluorescent DCF. The intensity of green fluorescence is proportional to the level of ROS in the cell. Figure 4 As shown in Figures 4a and 4b, the ROS content in untreated LoVo cells was 9.05%. After incubation with NHC-Ag2 and NHC-Ag / Au (4 μM) for 6 hours, the ROS content in LoVo cells increased significantly to 64.52% and 65.41%, respectively. The excessive production of ROS also indicates that the mitochondrial membrane potential in LoVo cells has been disrupted.

[0051] Mitochondrial membrane potential depolarization and excessive production of reactive oxygen species can trigger a series of intracellular events, ultimately leading to cell apoptosis or necrosis. LoVo cells were incubated with NHC-Ag2 and NHC-Ag / Au (4μM) for 24 hours. After Annexin V / PI double staining, flow cytometric analysis showed that the number of late apoptotic cells increased to 23.2% and 25.0%, respectively, while the number of premature apoptotic cells accounted for only 5.77% and 9.06% ( Figure 5 This indicates that under the action of NHC-Ag2 and NHC-Ag / Au, LoVo cells mainly die through late apoptosis. The increase in late apoptosis is generally considered to be a cell death caused by the necrosis pathway, which is different from the mode of action of platinum compounds, which mainly induces cell apoptosis through premature apoptosis.

[0052] The present invention synthesizes a homonuclear NHC-silver compound (NHC-Ag2) and a heteronuclear NHC-silver / gold (NHC-Ag / Au) bimetallic complex by functionalizing an imidazole salt with a phenanthroline group. The structure of the complex is confirmed by nuclear magnetic resonance and X-ray diffraction. In vitro anticancer activity studies have shown that NHC-Ag2 and NHC-Ag / Au both exhibit anticancer activity superior to or equivalent to cisplatin in the tested cancer cells. Anticancer mechanism studies in LoVo cells have shown that NHC-Ag2 and NHC-Ag / Au cause excessive production of intracellular reactive oxygen species by destroying the mitochondrial membrane potential, thereby causing cell necrosis. Compared with platinum drugs, silver and gold complexes have different modes of action in cancer cells and are studied in the treatment of platinum-resistant cancers.

[0053] It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above and that the invention can be embodied in other specific forms without departing from the spirit or essential characteristics of the invention. Therefore, the embodiments should be considered in all respects as illustrative and non-restrictive, and the scope of the invention is defined by the appended claims, not the foregoing description, and all variations within the meaning and range of equivalents of the claims are intended to be included therein. Any reference sign in a claim should not be construed as limiting the claim to which it relates.

[0054] In addition, it should be understood that although this specification is described in terms of implementation methods, not every implementation method contains only one independent technical solution. This narrative method of the specification is only for the sake of clarity. Those skilled in the art should regard the specification as a whole. The technical solutions in each embodiment can also be appropriately combined to form other implementation methods that can be understood by those skilled in the art.

Claims

1. Phenanthroline-functionalized nitrogen heterocyclic carbene binuclear silver NHC-Ag2 compounds and heteronuclear silver / gold NHC-Ag / Au compounds, characterized by: The structural formulas of the binuclear silver NHC-Ag2 compound and the heteronuclear silver / gold NHC-Ag / Au compound are as follows: 。 2. A method for preparing a phenanthroline-functionalized nitrogen heterocyclic carbene binuclear silver NHC-Ag2 compound and a heteronuclear silver / gold NHC-Ag / Au compound according to claim 1, characterized in that: The specific steps include: The first step is the preparation of phenanthroline functionalized imidazolium salt ligand HLPF6; The second step is the preparation of binuclear nitrogen heterocyclic carbene silver compound NHC-Ag2; The third step is the preparation of heteronuclear nitrogen heterocyclic carbene silver / gold compound NHC-Ag / Au; 。 3. The method for preparing a phenanthroline-functionalized nitrogen heterocyclic carbene binuclear silver NHC-Ag2 compound and a heteronuclear silver / gold NHC-Ag / Au compound according to claim 2, characterized in that: The specific steps include: 1,10-phenanthroline-2-imidazole and benzyl chloride were dissolved in acetonitrile and heated to reflux. After the reaction, the mixture was cooled and the acetonitrile solvent was removed. Deionized water was added to fully dissolve the solid matter in the reaction flask. The mixture was filtered and the filtrate was collected. A saturated aqueous solution of ammonium hexafluorophosphate was added dropwise to the filtrate to immediately precipitate a large amount of white solid. The solid compound was collected by suction filtration, washed three times with deionized water, and then dried to obtain the white phenanthroline-functionalized imidazole salt ligand HLPF6.

4. The method for preparing a phenanthroline-functionalized nitrogen heterocyclic carbene binuclear silver NHC-Ag2 compound and a heteronuclear silver / gold NHC-Ag / Au compound according to claim 2, characterized in that: The method specifically comprises the following steps: functionalizing an imidazole salt ligand HLPF6 with a phenanthroline functional group, mixing silver oxide in acetonitrile, heating, reacting in the dark, filtering the solution through a short silica gel column after the black silver oxide powder disappears, collecting the clear filtrate, transferring the filtrate to a test tube, and slowly volatilizing and recrystallizing the ether to obtain a binuclear nitrogen heterocyclic carbene silver compound.

5. The method for preparing a phenanthroline-functionalized nitrogen heterocyclic carbene binuclear silver NHC-Ag2 compound and a heteronuclear silver / gold NHC-Ag / Au compound according to claim 2, characterized in that: Phenanthroline-functionalized imidazolium salt ligand HLPF6 and silver oxide were mixed in acetonitrile and heated. After the reaction in the dark, (Et2S)AuCl was added and stirring was continued at room temperature. After the reaction was completed, the solution was centrifuged and filtered through a short silica gel column to collect the clear filtrate. The filtrate was transferred to a test tube and recrystallized from diethyl ether to obtain the heteronuclear nitrogen heterocyclic carbene silver / gold compound NHC-Ag / Au.

6. The method for preparing a phenanthroline-functionalized nitrogen heterocyclic carbene binuclear silver NHC-Ag2 compound and a heteronuclear silver / gold NHC-Ag / Au compound according to claim 5, characterized in that: The two central Ag(I) ions of the NHC-Ag2 cation are coordinated to two functionalized nitrogen heterocyclic carbene ligands in different ways.

7. The method for preparing a phenanthroline-functionalized nitrogen heterocyclic carbene binuclear silver NHC-Ag2 compound and a heteronuclear silver / gold NHC-Ag / Au compound according to claim 6, characterized in that: The Ag(I) ion is coordinated to the C atoms of the two carbene ligands in a linear manner, with a C-Ag-C bond angle of 172.5° and Ag-C bond lengths of 2.092 and 2.094 Å, respectively. The Ag(2) ion is coordinated to the four N atoms of the two phenanthroline ligands in a tetrahedral configuration, with Ag-N bond lengths of 2.219, 2.260, 2.438 and 2.457 Å, respectively.

8. The method for preparing a phenanthroline-functionalized nitrogen heterocyclic carbene binuclear silver NHC-Ag2 compound and a heteronuclear silver / gold NHC-Ag / Au compound according to claim 7, characterized in that: The cation of NHC-Ag / Au contains two phenanthroline-functionalized nitrogen heterocyclic carbene ligands, an Ag(I) ion and an Au(I) ion. In NHC-Ag / Au, the Ag(I) ion is coordinated to the four N atoms of the four phenanthrolines in a distorted tetrahedral configuration, and the Au(I) is coordinated to the two carbene C atoms in a linear manner. The C-Au-C bond angle is 176.2°, and the Au-C bond lengths are 2.007 and 2.018 Å, respectively.

9. Use of a phenanthroline-functionalized nitrogen heterocyclic carbene binuclear silver NHC-Ag2 compound and a heteronuclear silver / gold NHC-Ag / Au compound according to any one of claims 1 to 8, characterized in that: Used for the preparation of drugs for the treatment of platinum-resistant diseases.

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