Difluoromethyl-substituted imidazole carbene metal complex as well as preparation method and application thereof

Abstract

The invention discloses a difluoromethyl-substituted imidazole carbene metal complex as well as a preparation method and application thereof, and belongs to the technical field of organic synthesis. Difluoromethyl is introduced into the imidazole carbene complex, weak interaction sites are provided, the whole complex molecule has a rigid configuration, and therefore the quantum yield of the imidazole carbene metal complex is increased. When lone pair electrons of imidazole carbene are bonded with metal atoms, the electron density of central metal is improved, so that the catalytic performance of the difluoromethyl substituted imidazole carbene metal complex can be enhanced. Moreover, the difluoromethyl-substituted imidazole carbene metal complex provided by the invention can be used as a fluorescent dye for biological imaging of cancer cells, has low toxicity, high cell uptake rate and penetrating power, and can enter HeLa cells to present biological imaging capability. In addition, the synthetic route of the imidazole carbene metal complex provided by the invention is simple.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a difluoromethyl-substituted imidazole carbene metal complex and a preparation method and application thereof. Background Art

[0002] As a strong ligand, carbene ligand has very important applications in coordination chemistry. Carbene has a strong advantage in designing carbene metal complexes in coordination chemistry due to its tunable structural characteristics. The nitrogen atom on its skeleton can introduce a variety of alkyl and aryl substituents to regulate the electronic effect and steric effect of the ligand. The commonly used design strategy is to introduce a trifluoromethyl group with strong electron-withdrawing effect or a substituent with large steric hindrance, such as an aromatic or heteroaryl group, at the N site.

[0003] Imidazole carbene is an important component of carbene and is often used in the design of organic light-emitting complexes. Imidazole carbene is used to design transition metal complexes such as nickel, iridium, palladium, platinum, and ruthenium with its strong σ electron-donating ability and tunable π electron-accepting ability. Transition metal atoms can orbitally couple with carbene carbon atoms to form metal-carbene carbon bonds with large MC bond energy. Therefore, imidazole carbene metal complexes are stable to water and oxygen. They can be used in display devices, organic light-emitting diodes, fluorescent probes, and specific labeling of biomolecules.

[0004] Existing imidazole carbene transition metal complexes often use N-alkyl or aryl imidazole salts as carbene precursors during the synthesis process, but the fluorescence quantum yield of the metal complexes synthesized using such precursor salts is not ideal. The quantum yield can be improved by expanding the π system of the ligand substituent, but the synthesis route is long and the steps are cumbersome. Therefore, new design ideas and angles are needed to improve and enhance the structure and photophysical properties of current imidazole carbene complexes.

[0005] However, due to the limitation of substituents on the N site, it is difficult to introduce weak interaction sites into imidazole carbene to design new coordination modes and catalytic applications, thus limiting the synthesis of new imidazole carbene transition metal complexes and the improvement of their photophysical properties. Summary of the invention

[0006] In order to solve the above technical problems, the present invention provides a difluoromethyl-substituted imidazole carbene metal complex and a preparation method and application thereof.

[0007] To achieve the above object, the present invention provides the following technical solutions:

[0008] The present invention provides a difluoromethyl-substituted imidazole carbene metal complex, the general structural formula of which is Formula A or Formula B;

[0009]

[0010] In formula A, R1 and R2 are independently one of aryl, alkyl, heteroaryl, benzyl, ester, halogen, and hydrogen; L is one of aryl, heteroaryl, alkyl, benzyl, ester, and halogen;

[0011] In formula B, L1 and L2 are independently one of aryl, heteroaryl, halogen, alkyl, and benzyl;

[0012] M in Formula A and Formula B is a metal atom.

[0013] The present invention introduces a difluoromethyl group into the imidazole carbene complex to provide a weak interaction site. The H atom provided by the difluoromethyl group can form a halogen bond and a hydrogen bond with the halogen and the chalcogen element on the ortho-metal of the imidazole carbene, so that the entire complex molecule has a rigid configuration, and the fluorescence quantum yield of the imidazole carbene metal complex is improved. In addition, when the lone pair of electrons of the imidazole carbene forms a bond with the metal atom, the electron density of the central metal is increased, so the catalytic performance of the difluoromethyl-substituted imidazole carbene metal complex can be enhanced.

[0014] More preferably, the aryl group in R1, R2, L, L1 and L2 includes one of phenyl and chlorobenzene.

[0015] More preferably, the alkyl group in R1, R2, L, L1 and L2 includes one of methyl, ethyl and butyl.

[0016] More preferably, the heteroaryl group in R1, R2, L, L1 and L2 includes one of pyrrole, pyridine and thiophene.

[0017] More preferably, the benzyl aryl in R1, R2, L, L1 and L2 includes one of benzyl chloride and benzyl bromide.

[0018] Further preferably, the halogen in R1, R2, L, L1 and L2 includes one of F, Cl, Br and I.

[0019] Further preferably, the ester group in R1, R2 and L includes one of methyl acetate and ethyl acetate.

[0020] Preferably, the metal atom is one of copper, gold, nickel, platinum, palladium, silver, chromium, molybdenum, tungsten, manganese, iridium, zinc, mercury, vanadium, ruthenium, rhodium, cobalt, technetium, niobium, osmium, tantalum, zirconium, hafnium, scandium, yttrium, and titanium, and more preferably one of gold, nickel, platinum, palladium, zinc, vanadium, tantalum, scandium, yttrium, and titanium.

[0021] The present invention provides a method for preparing a difluoromethyl-substituted imidazole carbene metal complex described in the above technical scheme, comprising the following steps: dissolving a difluoromethyl-substituted imidazole salt in an organic solvent, then adding a metal source, and reacting at room temperature to obtain the difluoromethyl-substituted imidazole carbene metal complex.

[0022] The present invention uses a difluoromethyl-substituted imidazole salt as a carbene precursor, introduces a difluoromethyl group into the precursor salt, provides a weak interaction site, and thus improves the rigidity and fluorescence quantum yield of the difluoromethyl-substituted imidazole carbene metal complex.

[0023] Preferably, the usage ratio of the difluoromethyl substituted imidazole salt, the metal source and the organic solvent is (0.5-0.8) mmol: (0.5-0.8) mmol: (10-15) mL.

[0024] Preferably, the difluoromethyl substituted imidazolium salt includes 3-benzyl-1-(difluoromethyl)-1H-benzimidazol-3-ium bromide, 1-(difluoromethyl)-3-(2-methyl-naphthalene)-1H-benzimidazol-3-ium bromide or 3-difluoromethyl-1-phenyl-1H-imidazole trifluoromethanesulfonate.

[0025] Further preferably, the preparation method of the 3-benzyl-1-(difluoromethyl)-1H-benzimidazole-3-onium bromide comprises the following steps: dissolving 1-(difluoromethyl)-1H-benzimidazole (CAS: 84941-15-1) and benzyl bromide in acetonitrile, reacting at 90°C for 12h to obtain the 3-benzyl-1-(difluoromethyl)-1H-benzimidazole-3-onium bromide; the amount ratio of the 1-(difluoromethyl)-1H-benzimidazole, benzyl bromide and acetonitrile is 1mmol: 1mmol: 10mL. Further preferably, after the 90°C reaction, rotary evaporation, addition of ether for washing and filtering are also included.

[0026] Further preferably, the preparation method of 1-(difluoromethyl)-3-(2-methyl-naphthalene)-1H-benzimidazole-3-onium bromide comprises the following steps: dissolving 1-(difluoromethyl)-1H-benzimidazole and 2-(bromomethyl)naphthalene in acetonitrile, reacting at 90°C for 12h to obtain 1-(difluoromethyl)-3-(2-methyl-naphthalene)-1H-benzimidazole-3-onium bromide; the amount ratio of 1-(difluoromethyl)-1H-benzimidazole, 2-(bromomethyl)naphthalene and acetonitrile is 1mmol:1mmol:10mL. Further preferably, after the reaction at 90°C, rotary evaporation, addition of ether for washing and filtering are also included.

[0027] Further preferably, the preparation method of 3-difluoromethyl-1-phenyl-1H-imidazole trifluoromethanesulfonate comprises the following steps: dissolving difluoromethyl imidazole in dimethylformamide under Ar atmosphere, then adding diphenyl iodonium trifluoromethanesulfonate and copper acetate, reacting at 100°C for 12h to obtain 3-difluoromethyl-1-phenyl-1H-imidazole trifluoromethanesulfonate; the amount ratio of difluoromethyl imidazole, dimethylformamide, diphenyl iodonium trifluoromethanesulfonate and copper acetate is 1mmol: 15mL: 0.8mmol: 0.1mmol. Further preferably, after the reaction at 100°C, rotary evaporation, addition of ether for washing and filtering are also included.

[0028] Preferably, the organic solvent comprises dichloromethane or dimethylformamide.

[0029] Preferably, the metal in the metal source is one of copper, gold, nickel, platinum, palladium, silver, chromium, molybdenum, tungsten, manganese, iridium, zinc, mercury, vanadium, ruthenium, rhodium, cobalt, technetium, niobium, osmium, tantalum, zirconium, hafnium, scandium, yttrium and titanium.

[0030] Preferably, the reaction time at room temperature is 12 hours.

[0031] The present invention also provides the use of the difluoromethyl-substituted imidazole carbene metal complex described in the above technical solution as a fluorescent dye or catalyst for cancer cell bioimaging.

[0032] Compared with the prior art, the present invention has the following advantages and technical effects:

[0033] The present invention introduces a difluoromethyl group into the imidazole carbene complex to provide a weak interaction site, so that the entire complex molecule has a rigid configuration, thereby improving the quantum yield of the imidazole carbene metal complex to above 0.93.

[0034] The difluoromethyl-substituted imidazole carbene metal complex provided by the present invention can be used as a fluorescent dye for cancer cell bioimaging, has low toxicity, high cell uptake rate and penetration ability, can enter HeLa cells, and exhibit bioimaging ability.

[0035] The synthesis route of the imidazole carbene metal complex provided by the invention is simple and the rigidity of the complex is improved. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] The drawings constituting a part of the present application are used to provide a further understanding of the present application. The illustrative embodiments and descriptions of the present application are used to explain the present application and do not constitute an improper limitation on the present application. In the drawings:

[0037] Figure 1The experimental results of low toxicity of (1-benzyl-3-(difluoromethyl)-benzimidazole)goldous chloride in cancer cells prepared in Example 1 of the present invention; wherein (a) is the cytotoxicity after adding MEM culture medium containing (1-benzyl-3-(difluoromethyl)-benzimidazole)goldous chloride to each well and incubating for 4 hours, and (b) is the cytotoxicity after co-culturing the cells with fresh culture medium or MTT instead of culture medium for 20 hours;

[0038] Figure 2 The flow cytometric analysis results of (1-benzyl-3-(difluoromethyl)-benzimidazole)golden chloride prepared in Example 1 of the present invention;

[0039] Figure 3 This is the emission spectrum of 1-phenyl-3-difluoromethyl-imidazole palladium dichloride in dichloromethane prepared in Example 3 of the present invention. DETAILED DESCRIPTION

[0040] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0041] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the present invention is further described in detail below with reference to the accompanying drawings and specific embodiments.

[0042] The room temperature in the embodiments of the present invention refers to "25±2°C".

[0043] Unless otherwise specified, the raw materials in the examples of the present invention were purchased from commercial sources.

[0044] Example 1

[0045] A method for preparing a difluoromethyl-substituted imidazole carbene metal complex, the specific steps are as follows:

[0046] (1) Dissolve 1 mmol of 1-(difluoromethyl)-1H-benzimidazole and 1 mmol of benzyl bromide in 10 mL of acetonitrile, react at 90° C. for 12 h, evaporate the solvent, add ether for washing, and filter to obtain a white solid 3-benzyl-1-(difluoromethyl)-1H-benzimidazole-3-bromide with a yield of 90%.

[0047] The synthetic route of 3-benzyl-1-(difluoromethyl)-1H-benzimidazol-3-ium bromide is:

[0048]

[0049] The H spectrum of the obtained 3-benzyl-1-(difluoromethyl)-1H-benzimidazol-3-ium bromide is: 1 H NMR (400MHz, CDCl3) δ12.02 (s, 1H), 8.80 (t, J = 56.4 Hz, 1H), 7.88 (d, J = 8.0 Hz) 7.62-7.49 (m, 9H), 5.92 (s, 2H); C spectrum: 13 C NMR (100MHz, CDCl3): δ105.7,94.0,92.0,91.0,90.7,77.6,76.8,72.0,15.1.

[0050] (2) Take 0.5 mmol of 3-benzyl-1-(difluoromethyl)-1H-benzimidazol-3-ium bromide obtained in step (1) and dissolve it in 10 mL of dichloromethane (DCM), add 0.5 mmol of tetrahydrothiophene gold chloride (thtAuCl), react at room temperature for 12 h, evaporate the solvent, and perform column chromatography on silica gel to obtain a white solid (1-benzyl-3-(difluoromethyl)-benzimidazol) gold chloride with a yield of 87%.

[0051] The synthetic route of (1-benzyl-3-(difluoromethyl)-benzimidazole)golden chloride is:

[0052]

[0053] The H spectrum of (1-benzyl-3-(difluoromethyl)-benzimidazole)golden chloride is: 1 H NMR (400MHz, CDCl3): δ8.03 (t, J = 58.0 Hz, 1H), 7.83 (d, J = 8.0 Hz, 1H), 7.52-7.36 (m, 8H), 5.76 (s, 2H). C spectrum: 13 CNMR (100MHz, CDCl3): δ149.7,136.1,130.5,128.5,126.9,126.7,118.6,117.9,53.0.

[0054] Example 2

[0055] A method for preparing a difluoromethyl-substituted imidazole carbene metal complex, the specific steps are as follows:

[0056] (1) Dissolve 1 mmol of 1-(difluoromethyl)-1H-benzimidazole and 1 mmol of 2-(bromomethyl)naphthalene in 10 mL of acetonitrile, react at 90° C. for 12 h, evaporate the solvent, add ether for washing, and filter to obtain a white solid 1-(difluoromethyl)-3-(2-methyl-naphthalene)-1H-benzimidazole-3-onium bromide with a yield of 96%.

[0057] The synthetic route of 1-(difluoromethyl)-3-(2-methyl-naphthalene)-1H-benzimidazol-3-ium bromide is:

[0058]

[0059] The H spectrum of the obtained 1-(difluoromethyl)-3-(2-methyl-naphthalene)-1H-benzimidazol-3-ium bromide is: 1 H NMR (400MHz,CDCl3)δ12.46(s,1H),8.84(t,J=56.0Hz,1H),8.02(s,1H),7.95(t,J=8.0Hz,1H),7.87-7.77(m,3H),7.67-7.48(m,6H),6.06(s,2H); C spectrum is: 13 C NMR (100MHz, CDCl3): δ151.8,137.0,135.2,133.7,135.0,131.8,131.7,13 1.6,128.0,127.6,127.5,127.3,127.0,126.5,126.2,126.0,125.1,58.9.

[0060] (2) Take 0.5 mmol of 1-(difluoromethyl)-3-(2-methyl-naphthalene)-1H-benzimidazol-3-ium bromide obtained in step (1) and dissolve it in 10 mL of dichloromethane (DCM), add 0.5 mmol of tetrahydrothiophene gold chloride (thtAuCl), react at room temperature for 12 h, evaporate the solvent, and perform column chromatography on silica gel to obtain a white solid difluoromethyl-substituted imidazole carbene gold complex, 96%.

[0061] The synthetic route of difluoromethyl substituted imidazole carbene gold complex is:

[0062]

[0063] The H spectrum of the difluoromethyl-substituted imidazole carbene gold complex is: 1 H NMR (400MHz, CDCl3): δ8.05 (t, J=60.0Hz, 1H), 7.84-7.82 (m, 5H), 7.53-7.42 (m, 6H), 5.92 (s, 2H). C spectrum:13 C NMR (100MHz, CDCl3): δ151.0,135.2,133.7,131.8,128.0,127.6,127.5,127.3,127.0,126.0,125.1,53.4.

[0064] Example 3

[0065] A method for preparing a difluoromethyl-substituted imidazole carbene metal complex, the specific steps are as follows:

[0066] (1) Under Ar atmosphere, 1 mmol of difluoromethylimidazole was dissolved in 15 mL of dimethylformamide, and then 0.8 mmol of diphenyliodonium trifluoromethanesulfonic acid and 0.1 mmol of copper acetate were added and reacted at 100°C for 12 h. The solvent was evaporated and the mixture was washed with ether and filtered to obtain 3-difluoromethyl-1-phenyl-1H-imidazole trifluoromethanesulfonate as a white solid.

[0067] The H spectrum of the obtained 3-difluoromethyl-1-phenyl-1H-imidazole trifluoromethanesulfonate is: 1 H NMR (600MHz, CDCl3): δ8.92 (s, 1H), 7.92 (d, J = 5.6 Hz, 1H), 7.84 (t, J = 56.7 Hz, 1H), 7.75 (d, J = 5.6 Hz, 1H), 7.36 (m, 5H), 6.75 (d, J = 8.0 Hz, 1H). C spectrum: 13 C NMR (150MHz, CDCl3): δ149.3, 143.8, 137.0, 134.1, 132.9, 130.0, 125.4, 123.4, 122.8.

[0068] (2) 0.8 mmol of 3-difluoromethyl-1-phenyl-1H-imidazole trifluoromethanesulfonate obtained in step (1) was dissolved in 15 mL of dimethylformamide, and then 0.8 mmol of silver oxide was added to react at room temperature for 24 hours, and then 0.8 mmol of (1,5-cyclooctadiene) palladium dichloride was added to react at room temperature for 12 hours. The solvent was evaporated and column chromatography was performed on silica gel to obtain a yellow-green solid 1-phenyl-3-difluoromethyl-imidazole palladium dichloride with a yield of 51%.

[0069] The synthetic route of 1-phenyl-3-difluoromethyl-imidazole palladium dichloride is:

[0070]

[0071] The H spectrum of the obtained 1-phenyl-3-difluoromethyl-imidazole palladium dichloride is: 1H NMR (600MHz, CDCl3): δ8.99(t,J=57.8Hz,1H),8.01(d,J=8.3Hz,1H),7.90(d,J=7.2Hz,1H) ,7.46(t,J=7.7Hz,1H),7.42(t,J=7.7Hz,1H),7.16(t,J=7.3Hz,1H),7.07(t,J=7.3Hz,1H). The C spectrum is: 13 C NMR (150MHz, CDCl3): δ186.0,185.4,161.9,147.3,131.8,131.3,125.3,124.3,124.0,113.8,112.4,112.3,111.4,110.6.

[0072] (1) Low cell toxicity experiment

[0073] Human cervical cancer cell line (HeLa) was selected as the experimental cell, and the activity of HeLa cells treated with (1-benzyl-3-(difluoromethyl)-benzimidazole) gold chloride prepared in Example 1 at different concentrations was evaluated using the MTT method. Cells were cultured on a biological experimental platform in a sterile room and a cell culture incubator according to standard procedures. The culture environment required a temperature of 37°C, a carbon dioxide content of 5%, and a relative humidity of 95%. First, HeLa cells were cultured at 1×10 4 The cells were inoculated into 96-well plates at a concentration of 100 μg / mL and incubated overnight. -1 Penicillin and 100 mg mL -1 Streptomycin) The (1-benzyl-3-(difluoromethyl)-benzimidazole) gold chloride prepared in Example 1 was diluted to different concentrations (0.5 μM, 1.5 μM, 2.5 μM, 5 μM, 7.5 μM, 10 μM, 15 μM), the original culture medium was aspirated, and then the MEM culture medium containing (1-benzyl-3-(difluoromethyl)-benzimidazole) gold chloride was added to each well. After incubation for 4 hours, the cells were co-cultured with fresh culture medium (the composition of the fresh culture medium was consistent with the original culture medium) for 20 hours, or co-cultured with MTT instead of culture medium (MEM culture medium containing (1-benzyl-3-(difluoromethyl)-benzimidazole) gold chloride) for 20 hours. After incubation for another 4 hours, 100 μL of dimethyl sulfoxide (DMSO) was added to each well, and the 96-well plate was analyzed using an ELISA reader. The results are shown in FIG. Figure 1 .

[0074] Figure 1The results of the low toxicity experiment of (1-benzyl-3-(difluoromethyl)-benzimidazole)goldous chloride prepared in Example 1 in cancer cells. (a) is the cytotoxicity after adding MEM medium containing (1-benzyl-3-(difluoromethyl)-benzimidazole)goldous chloride to each well and incubating for 4 hours, and (b) is the cytotoxicity after co-culturing the cells with fresh medium or MTT instead of medium for 20 hours. Figure 1 It can be seen that the (1-benzyl-3-(difluoromethyl)-benzimidazole) gold(II) chloride complex prepared in Example 1 of the present invention has low toxicity.

[0075] (2) Flow cytometry

[0076] First, 1×10 5 Hela cells were inoculated in a 20 mm cell culture dish and incubated for 24 h. -1 Penicillin and 100 mg mL -1 Streptomycin) The (1-benzyl-3-(difluoromethyl)-benzimidazole) gold chloride prepared in Example 1 was diluted to different concentrations (0.5 μM, 1.5 μM, 2.5 μM, 5 μM, 7.5 μM, 10 μM, 15 μM), added to the cell culture dish and incubated for 4 hours. The cells treated with (1-benzyl-3-(difluoromethyl)-benzimidazole) gold chloride were washed three times with sterile PBS and digested with 0.05% trypsin-EDTA at 37°C for 3 minutes to obtain 7 complexes. The percentage of positive cells in the 7 complexes was detected by flow cytometry. The results are shown in Figure 2 .

[0077] Figure 2 The flow cytometric analysis results of (1-benzyl-3-(difluoromethyl)-benzimidazole) gold chloride prepared in Example 1. Figure 2 It can be seen that the (1-benzyl-3-(difluoromethyl)-benzimidazole)golden chloride prepared by the present invention has a high cell uptake rate and strong cell spheroplast ability, so it can enter HeLa cells and exhibit biological imaging capabilities.

[0078] (3) Fluorescence experiment

[0079] The 1-phenyl-3-difluoromethyl-imidazole palladium dichloride prepared in Example 3 was dissolved in dichloromethane to prepare a solution with a concentration of 5×10 -5 mol / L solution, at room temperature, with an excitation wavelength of 315 nm, the luminescence performance was tested. The test results are shown in Figure 3 .

[0080] Figure 3 This is the emission spectrum of 1-phenyl-3-difluoromethyl-imidazole palladium dichloride in dichloromethane prepared in Example 3. Figure 3 It can be seen that the 1-phenyl-3-difluoromethyl-imidazole palladium dichloride prepared in Example 3 has the photophysical property of emitting fluorescence and has a good quantum yield.

[0081] The above are only preferred specific implementations of the present application, but the protection scope of the present application is not limited thereto. Any changes or substitutions that can be easily thought of by a person skilled in the art within the technical scope disclosed in the present application should be included in the protection scope of the present application. Therefore, the protection scope of the present application should be based on the protection scope of the claims.

Claims

1. A difluoromethyl-substituted imidazole carbene metal complex, characterized in that: Its general structural formula is formula A or formula B; In formula A, R1 and R2 are independently one of aryl, alkyl, heteroaryl, benzyl, ester, halogen, and hydrogen; L is one of aryl, heteroaryl, alkyl, benzyl, ester, and halogen; In formula B, L1 and L2 are independently one of aryl, heteroaryl, halogen, alkyl, and benzyl; M in Formula A and Formula B is a metal atom.

2. The difluoromethyl-substituted imidazole carbene metal complex according to claim 1, characterized in that The metal atom is one of copper, gold, nickel, platinum, palladium, silver, chromium, molybdenum, tungsten, manganese, iridium, zinc, mercury, vanadium, ruthenium, rhodium, cobalt, technetium, niobium, osmium, tantalum, zirconium, hafnium, scandium, yttrium, and titanium.

3. The difluoromethyl-substituted imidazole carbene metal complex according to claim 2, characterized in that: The metal atom is one of gold, nickel, platinum, palladium, zinc, vanadium, tantalum, scandium, yttrium and titanium.

4. A method for preparing the difluoromethyl-substituted imidazole carbene metal complex according to any one of claims 1 to 3, characterized in that: The following steps are involved: The difluoromethyl substituted imidazole salt is dissolved in an organic solvent, and then a metal source is added to react at room temperature to obtain the difluoromethyl substituted imidazole carbene metal complex.

5. The preparation method according to claim 4, characterized in that: The usage ratio of the difluoromethyl substituted imidazole salt, the metal source and the organic solvent is (0.5-0.8) mmol: (0.5-0.8) mmol: (10-15) mL.

6. The preparation method according to claim 4, characterized in that: The difluoromethyl substituted imidazolium salts include 3-benzyl-1-(difluoromethyl)-1H-benzimidazol-3-ium bromide, 1-(difluoromethyl)-3-(2-methyl-naphthalene)-1H-benzimidazol-3-ium bromide or 3-difluoromethyl-1-phenyl-1H-imidazole trifluoromethanesulfonate.

7. The preparation method according to claim 4, characterized in that: The organic solvent includes dichloromethane or dimethylformamide.

8. The preparation method according to claim 4, characterized in that: The metal in the metal source is one of copper, gold, nickel, platinum, palladium, silver, chromium, molybdenum, tungsten, manganese, iridium, zinc, mercury, vanadium, ruthenium, rhodium, cobalt, technetium, niobium, osmium, tantalum, zirconium, hafnium, scandium, yttrium and titanium.

9. The preparation method according to claim 4, characterized in that: The reaction time at room temperature is 12 hours.

10. Use of the difluoromethyl-substituted imidazole carbene metal complex according to any one of claims 1 to 3 as a fluorescent dye or catalyst for cancer cell bioimaging.

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