Gold complexes with aggregation-induced emission characteristic as well as preparation method and application of gold complexes

Abstract

The invention provides a gold complex with an aggregation-induced emission characteristic as well as a preparation method and application thereof, and belongs to the field of metal organic compounds. The structural formula of the gold complex disclosed by the invention is as follows: # imgabs0 #. The gold complex prepared by the invention can effectively inhibit the growth of fungi at low concentration, shows extremely strong antifungal activity, has very small toxicity to normal cells, has good biocompatibility, can perform fluorescent visual imaging on fungal infection, and provides powerful support for diagnosis.

Description

Technical Field

[0001] The present invention relates to the field of metal organic compounds, and particularly to a class of gold complexes with aggregation-induced emission characteristics, their preparation methods and applications. Background Art

[0002] In recent years, fungal pathogen infections have posed a serious threat to human health. There are up to 1.5 million fatal complications caused by fungal infections every year, especially significant in immunocompromised populations. Currently, there are limited types of antifungal drugs in clinical practice, and they have serious side effects.

[0003] Moreover, the current drugs for treating fungal pathogen infections cannot be visualized, which limits the research of antifungal drugs. Therefore, there is a need for low-toxic and highly effective drugs with both significant antifungal and visualization properties. Summary of the Invention

[0004] The purpose of the present invention is to provide a class of gold complexes with aggregation-induced emission characteristics, their preparation methods and applications. The gold complexes prepared by the present invention can completely inhibit fungal growth at low concentrations, exhibit extremely strong antifungal activity, and have little toxicity to normal cells and good biocompatibility.

[0005] In order to achieve the above invention purposes, the present invention provides the following technical solutions: The present invention provides a class of gold complexes with aggregation-induced emission characteristics, and the structural formula of the gold complexes is shown as follows: 。

[0006] The present invention provides a preparation method of the above gold complexes, and the synthesis routes of the gold complexes 1-5 are as follows: , , , , Preferably, the preparation methods of the gold complexes 1 and 2 are as follows: Under a nitrogen atmosphere, KPF6, 4, and ligand raw materials are mixed to obtain a mixed material, and then after vacuum pumping and nitrogen replacement, dry DCM and dry methanol are added and stirred at room temperature for 24 h. After the reaction ends, it is successively subjected to extraction, anhydrous sodium sulfate drying, filtration, and evaporation to obtain a crude product; the crude product is recrystallized to obtain the target product; When the ligand raw material is PPh3, gold complex 1 is obtained; When the ligand raw material is PCy3, gold complex 2 is obtained.

[0007] Preferably, the molar ratio of the KPF6, 4, and ligand raw materials is (2.8 - 3.2):(1.8 - 2.2):(1.8 - 2.2); The mass - volume ratio of the mixture, dry DCM, and dry methanol is (130 - 150) mg:(15 - 25) mL:(8 - 12) mL.

[0008] Preferably, the preparation method of the gold complex 3 is as follows: Under a nitrogen atmosphere, potassium carbonate, 1d, and 3a are mixed to obtain a mixture, and then stirred at room temperature for 24 h. After the reaction is completed, it is successively subjected to extraction, drying with anhydrous sodium sulfate, filtration, and evaporation to obtain a crude product; the crude product is recrystallized to obtain the target product.

[0009] Preferably, the molar ratio of potassium carbonate, 1d, and 3a is (0.8 - 1.2):(0.4 - 0.6):(0.4 - 0.6).

[0010] Preferably, the extraction is independently carried out using ethyl acetate and water.

[0011] Preferably, the evaporation is independently carried out under reduced pressure.

[0012] Preferably, the recrystallization is independently carried out using CH2Cl2 / n - hexane.

[0013] Preferably, the preparation method of the gold complex 4 is as follows: Under a nitrogen atmosphere, 1d and silver oxide are mixed to obtain a mixture, and then after evacuation and nitrogen replacement, degassed dichloromethane is added and stirred at room temperature in the dark for 48 h under nitrogen. Then, thiophene chloride gold is added, and stirring is continued at room temperature for 12 h. After the reaction is completed, it is successively subjected to filtration, concentration under reduced pressure, separation and purification, and then precipitated with dichloromethane / n - hexane to obtain the target product.

[0014] Preferably, the molar ratio of 1d, silver oxide, and thiophene chloride gold is (13 - 18):(6 - 10):(13 - 18); The mass - volume ratio of the mixture and degassed dichloromethane is (95 - 105) mg:(18 - 22) mL.

[0015] Preferably, the preparation method of the gold complex 5 is as follows: Under a nitrogen atmosphere, 5b and silver oxide are mixed to obtain a mixture, and then after evacuation and nitrogen replacement, degassed methanol is added and stirred at room temperature in the dark for 48 h under nitrogen. Then, sodium chloride and thiophene chloride gold are added, and stirring is continued at room temperature for 12 h. After the reaction is completed, it is successively subjected to filtration, concentration under reduced pressure, separation and purification, and then precipitated with dichloromethane / n - hexane to obtain the target product.

[0016] Preferably, the molar ratio of the 5b, silver oxide, sodium chloride, and chloroauric acid tetrahydrothiophene is (13 - 16):(6 - 10):(13 - 16):(13 - 16); The mass - volume ratio of the mixture and degassed methanol is (95 - 105) mg:(25 - 35) mL.

[0017] Preferably, the separation and purification are each independently carried out by column chromatography using neutral alumina.

[0018] The present invention also provides the application of the above - mentioned gold complex in the visualization of fungal infection and / or in drugs for treating fungal infection.

[0019] Compared with the prior art, the present invention has the following beneficial effects: 1. The gold complex with aggregation - induced emission characteristics prepared by the present invention can completely inhibit the growth of fungi at low concentrations, showing extremely strong antifungal activity, and having little toxicity to normal cells and good biocompatibility.

[0020] 2. The gold complex prepared by the present invention has excellent AIE characteristics and can perform fluorescence visualization imaging on fungal infection, providing strong support for diagnosis.

[0021] 3. Experiments prove that the gold complex prepared by the present invention significantly accelerates the healing rate of fungal - infected wounds. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 Photoluminescence spectra of gold complex 1 in mixed solvents of different ratios of CH3CN / H2O.

[0023] Figure 2 Photoluminescence spectra of gold complex 2 in mixed solvents of different ratios of CH3CN / H2O.

[0024] Figure 3 Photoluminescence spectra of gold complex 3 in mixed solvents of different ratios of CH3CN / H2O.

[0025] Figure 4 Photoluminescence spectra of gold complex 4 in mixed solvents of different ratios of THF / H2O.

[0026] Figure 5 Photoluminescence spectra of gold complex 5 in mixed solvents of different ratios of THF / H2O.

[0027] Figure 6 In vitro antibacterial effects of five gold complexes; standard Candida albicans (ATCC 14053).

[0028] Figure 7 For the in vitro antibacterial effects of five gold complexes; standard Candida parapsilosis (ATCC 22019).

[0029] Figure 8 For the in vitro antibacterial effects of five gold complexes; standard Candida glabrata (ATCC MYA 2950).

[0030] Figure 9 For the in vitro antibacterial effects of five gold complexes; standard Candida krusei (ATCC 14243).

[0031] Figure 10 For the in vitro antibacterial effects of five gold complexes; standard Candida tropicalis (ATCC 1369).

[0032] Figure 11 For the CCK8 cytotoxicity assay analysis of the co-incubation of five gold complexes with human normal liver (LO2) cells and human umbilical vein endothelial (HUVEC) cells respectively.

[0033] Figure 12 For the treatment effect diagram of mouse wound fungal infection.

[0034] Figure 13 For the visualization imaging of five AIE gold complexes on standard Candida albicans and Candida tropicalis respectively.

[0035] Figure 14 For the visualization imaging of five AIE gold complexes on standard Candida krusei and Candida parapsilosis respectively.

[0036] Figure 15 For the visualization imaging of five AIE gold complexes on standard Candida glabrata respectively. Detailed implementation manners

[0037] Now, various exemplary implementation manners of the present invention will be described in detail. This detailed description should not be regarded as a limitation of the present invention, but should be understood as a more detailed description of certain aspects, characteristics and implementation schemes of the present invention.

[0038] It should be understood that the terms described in the present invention are only for describing specific implementation manners and are not used to limit the present invention. In addition, for the numerical ranges in the present invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Each intermediate value within any stated value or stated range, as well as each smaller range between any other stated value or intermediate value within the stated range, is also included in the present invention. The upper and lower limits of these smaller ranges can be independently included or excluded within the range.

[0039] Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Although this invention only describes preferred methods and materials, any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of this invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials related to the said documents. In case of conflict with any incorporated document, the content of this specification shall prevail.

[0040] Without departing from the scope or spirit of the present invention, various modifications and variations can be made to the specific embodiments of the description of the present invention, which are obvious to those skilled in the art. Other embodiments obtained from the description of the present invention are obvious to those skilled in the art. The description and examples of this application are merely exemplary.

[0041] Regarding the use of "comprising", "including", "having", "containing", etc. herein, they are all open-ended terms, meaning including but not limited to.

[0042] As used in this invention, "room temperature" and "normal temperature" are both calculated as 25 ± 2 °C unless otherwise specified.

[0043] Unless otherwise specified, the raw materials used in the following examples of this invention are all obtained commercially.

[0044] The synthetic routes of gold complexes 1 - 5 are as follows: , , , , The following examples are prepared with reference to the above synthetic routes, and the synthetic raw materials used are those described in the synthetic routes. For example, 4 in Example 1 represents .

[0045] Example 1 This example provides a gold complex with aggregation-induced emission properties, and the preparation method is as follows: Dry a 50 mL two-necked flask and a T-shaped three-way joint in a drying oven for 30 min, then evacuate the reaction device for 10 min and introduce a nitrogen gas stream.

[0046] Under a nitrogen atmosphere, KPF6 (0.24 mmol, 44.2 mg), 4 (0.16 mmol, 51.5 mg) and PPh3 (0.16 mmol, 42.0 mg) were added to a reaction flask, evacuated for 15 min, and replaced with nitrogen three times; then 0.3 of ultra-dry DCM (20 mL) and 0.25 of ultra-dry methanol (10 mL) were added separately using a syringe, and stirred at room temperature for 24 hours; after the reaction stopped, it was extracted with ethyl acetate and water, the organic phases were combined, dried over anhydrous sodium sulfate; filtered; the filtrate was removed by evaporation under reduced pressure to obtain the crude product.

[0047] The crude product was separated and purified by a chromatography column, and then recrystallized with CH2Cl2 / n-hexane to obtain the target product as a white solid.

[0048] The product is as follows: Yield: 65 mg (80 %) 1 H NMR (400 MHz, CD3CN): δ 7.62 - 7.53 (m, 15H, CH aromatic PPh3), 7.40(s, 1H, CH imidazole), 7.33 (s, 1H, CH imidazole), 7.25 (d, J = 8.0 Hz, 2H, CHaromatic TPE), 7.16 - 6.91 (m, 17H, CH aromatic TPE), 3.71 (s, 3H, CH3); 13 C NMR(100 MHz, CD3CN): δ 182.8 (NCN carbene), 144.8, 143.4, 143.4, 143.2, 142.4,139.9, 137.6, 134.4, 134.4, 132.6, 131.9, 131.0, 130.6, 129.6, 129.4, 128.4,127.9, 127.5, 126.8, 126.9, 126.4, 124.6, 123.7, 122.4, 37.6; 31 P NMR (160 MHz,CD3CN): 44.0, -144.7; HRMS: m / z: [M - PF6] + calcd for [C 48 H 39 AuN2P] +: 871.2511; found: 871.2510. Example 2 This example provides a gold complex with aggregation-induced emission properties, and the preparation method is as follows: Dry a 50 mL two-necked flask and a T-shaped three-way joint required for the reaction in an oven for 30 min, then evacuate the reaction device for 10 min and introduce a nitrogen gas stream.

[0049] Under a nitrogen atmosphere, add KPF6 (0.24 mmol, 44.2 mg), 4 (0.16 mmol, 51.5 mg), and PCy3 (0.16 mmol, 44.8 mg) into the reaction flask, evacuate for 15 min, and replace with nitrogen three times. Then, add ultradry DCM (20 mL) and ultradry methanol (10 mL) separately using a syringe, and stir at room temperature for 24 h; after the reaction stops, extract with ethyl acetate and water, combine the organic phases, dry with anhydrous sodium sulfate; filter; evaporate the filtrate under reduced pressure to obtain the crude product.

[0050] Purify the crude product by column chromatography, and then recrystallize with CH2Cl2 / n-hexane to obtain a white solid product.

[0051] The product is: Yield: 110.9 mg (78 %) Example 3 This example provides a gold complex with aggregation-induced emission properties, and the preparation method is as follows: Dry a 50 mL two-necked flask and a T-shaped three-way joint required for the reaction in an oven for 30 min, then evacuate the reaction device for 10 min and introduce a nitrogen gas stream.

[0052] Under a nitrogen atmosphere, add potassium carbonate (1 mmol, 138 mg), 1d (0.5 mmol, 270 mg), and 3a (0.5 mmol, 311 mg) into the reaction flask; stir the mixture at room temperature for 24 h; after the reaction stops, extract with ethyl acetate and water, combine the organic phases, dry with anhydrous sodium sulfate; filter, and evaporate the filtrate under reduced pressure to obtain the crude product.

[0053] Purify the crude product by column chromatography, and then recrystallize with dichloromethane / n-hexane to obtain a white solid product.

[0054] The product is: Yield: 217 mg (65 %) 11H NMR (400 MHz, CD2Cl2): δ 7.46 (t, J J = 8.0 Hz, 2H), 7.34 (s, 2H, CHimidazole), 7.27 - 7.22 (m, 8H, CH imidazole and aromatic), 7.16 - 7.02 (m, 13H,CHaromatic), 6.98 (d, J J = 12.0 Hz, 2H, CH aromatic), 6.73 (d, J J = 8.0 Hz, 2H, CHaromatic), 3.11 (s, 3H, N - CH3), 2.50 (m, 4H, CH(CH3)2isopropyl), 1.23 - 1.16(dd, J J = 4.0 Hz, 24 H, CH(CH3)2isopropyl); 13 13C NMR (100 MHz, CD2Cl2): δ 187.0((NCN - TPE carbene)), 181.5 (NCN carbene), 146.6, 143.6, 143.5, 143.4, 143.2,139.4, 136.2, 134.0, 132.5, 131.4, 131.3, 131.2, 128.4, 128.2, 128.1, 127.5,127.4, 127.1, 124.6, 124.5, 121.6, 37.9 (N - CH3), 29.5 (CH(CH3)2isopropyl),24.6 (CH(CH3)2isopropyl), 24.4 (CH(CH3)2isopropyl); HRMS: m / z: [M - I] + calcd forC 57 H 60 AuN4 + : 997.4478; found: 997.4468. Example 4 This example provides a gold complex with aggregation - induced emission properties, and the preparation method is as follows: Dry a 50 mL two - necked flask and a T - shaped three - way valve in a drying oven for 30 min, then evacuate the reaction device for 10 min and introduce a nitrogen gas stream.

[0055] Under a nitrogen atmosphere, 1d (0.15 mmol, 81.0 mg) and silver(I) oxide (0.08 mmol, 18.0 mg) were placed in a reaction flask, evacuated for 15 min, and purged with nitrogen three times. Then, degassed dichloromethane (20 mL) was added using a syringe, and the mixture was stirred at room temperature in the dark under nitrogen for 48 h. Then, thiothene chloroaurate (0.15 mmol, 48.0 mg) was added, and stirring was continued at room temperature for 12 h. After the reaction stopped, it was filtered through diatomaceous earth, the filtrate was concentrated under reduced pressure and removed, and then purified by column chromatography on neutral alumina. Then, it was precipitated with dichloromethane / n-hexane to obtain a white solid product.

[0056] The product is: Yield: 79.2 mg (82 %) 1 H NMR (400 MHz, CDCl3): δ 7.34 (s, 1H, CH imidazole), 7.32 (s, 1H, CHimidazole), 7.17 - 7.03 (m, 19H, CH aromatic TPE), 3.93 (s, 3H); 13 C NMR (100MHz, CDCl3): δ 170.6, 144.8, 143.5, 143.4, 143.3, 142.7, 139.6, 137.0, 132.8,131.7, 131.3, 128.5, 128.0, 127.6, 127.4, 126.6, 126.4, 123.9, 122.6, 121.4,46.0 (CH3); HRMS: m / z: [M] + calcd for C 30 H 24 AuClN2 + : 644.1294; found: 644.1242. Example 5 This example provides a gold complex with aggregation-induced emission properties, and the preparation method is as follows: A 50 mL two-necked flask and a T-shaped three-way joint required for the reaction were dried in an oven for 30 min, and then the reaction apparatus was evacuated for 10 min and a nitrogen gas stream was introduced.

[0057] Under a nitrogen atmosphere, 5b (0.15 mmol, 78.1 mg) and silver oxide (0.08 mmol, 18.0 mg) were added to a reaction flask. The flask was evacuated for 15 min and purged with nitrogen three times; then degassed methanol (30 mL) was added using a syringe; then the mixture was stirred at room temperature in the dark under nitrogen for 48 h; then sodium chloride (0.15 mmol, 8.7 mg) and chloroauric acid tetrahydrothiophene complex (0.15 mmol, 48.0 mg) were added, and stirring was continued at room temperature for 12 h; after the reaction stopped, it was filtered through diatomaceous earth, and the filtrate was concentrated under reduced pressure and removed; then it was separated and purified by neutral alumina column chromatography, and then precipitated with methanol / ether to obtain a white solid product.

[0058] The product is: Yield: 77.9 mg (67%) Experimental Example 1 The AIE gold complexes obtained in Examples 1-5 were physically characterized, including ultraviolet-visible absorption spectra, compound excitation spectra, and compound emission spectra.

[0059] Five AIE gold complexes were dissolved in DMF and pure water respectively to prepare stock solutions of the compounds, with their concentration contents being 5 mmol / L and 500 μmol / L. Their ultraviolet-visible absorption spectra were measured using an ultraviolet-visible spectrophotometer, and their excitation spectra and emission spectra were measured using a fluorescence spectrometer.

[0060] In order to explore the AIE properties of the five AIE gold complexes, their fluorescence emission properties in different solvent systems were measured respectively. THF was the effective solvent for the target gold complex, and H2O was the poor solvent for the target gold complex. The fluorescence properties of the five AIE gold complexes in DMF / H2O solvent systems with different H2O volume fractions ( f w ) were explored. Using the previously prepared and dissolved stock solutions, solvent systems with H2O volume fractions ( f w ) of 99%, 90%, 80%, 70%, 60%, 50%, 40%, 30%, 20%, 10%, and 0% were prepared. A THF / H2O mixed solution with a final concentration of 50 μmol / L of the five AIE gold complexes was thoroughly mixed, and the photoluminescence spectra of these 11 groups of solutions were measured at an excitation wavelength of 560 nm. Figures 1-3 Photoluminescence spectra of AIE gold complexes 1-3 in CH3CN / H2O mixed solvents with different ratios, respectively; Figures 4-5 Photoluminescence spectra of AIE gold complexes 4-5 in tetrahydrofuran (THF) / H2O mixed solvents with different ratios, respectively.

[0061] Experimental Example 2 The AIE gold complexes obtained in Examples 1-5 were subjected to bioactivity tests: The invasive fungi used included standard strains (Candida albicans, Candida glabrata, Candida tropicalis, Candida parapsilosis, Candida krusei) and strains resistant to azole drugs respectively.

[0062] Experimental preparation: Alcohol disinfect the experimental consumables such as YPD agar medium plates (prepared in advance), sterile centrifuge tubes, micropipettes, sterile pipette tips, disposable sterile inoculation loops, sterile plastic EP tubes, disposable sterile spreading rods, etc., and then place them in the biosafety cabinet for routine ultraviolet sterilization for 30 min. Experimental operations can be carried out only after 30 min of disinfection under ultraviolet light.

[0063] Experimental operators need to take corresponding biosafety protection measures, such as wearing protective work clothes, masks, hats and special experimental nitrile sterile gloves, etc. Use a degreasing cotton ball soaked in 75% alcohol to wipe the operating table of the biosafety cabinet again in the biosafety cabinet.

[0064] Experimental steps: First, prepare the fungal suspension. Take out the revived fungal liquid and put it into the biosafety cabinet. Take 20 mL of the fungal liquid in the centrifuge tube in the safety cabinet. Then place the centrifuge tube in the centrifuge and centrifuge for 15 min (3500 rpm) to remove the supernatant to obtain the cell pellet. After that, add PBS for washing and centrifuge again for 15 min (3500 rpm). In this way, the cell pellet is washed with PBS repeatedly for 3 times. After washing, use PBS to prepare a resuspended bacterial liquid. Use a turbidimeter to measure the turbidity of the resuspended bacterial liquid and adjust the turbidity to 0.5 for standby. At this time, it is equivalent to a bacterial liquid concentration of 0.5×10 7 CFU / mL.

[0065] When detecting the bactericidal effect of the new gold complex on invasive fungi, use disposable plastic EP tubes. According to different concentrations of the gold complex, set six groups, namely PBS control group, 2.5 μmol / L, 5 μmol / L, 10 μmol / L, 12.5 μmol / L, 15 μmol / L. Configure the reaction system in the EP tube according to different concentration groups, mix the fungal liquid and the gold complex molecules together for co-culture, and the reaction concentration of the bacterial liquid is 1×10 4CFU / mL. After preparing the reaction system, mix it using a shaker, place it in an incubator at 35°C with 5% CO2 for 0.5 h. Then take out the EP tubes, mix again using the shaker, and in a biosafety cabinet, use a micropipette to aspirate 100 μL of the mixed solution from each group of EP tubes and add it to the YPD agar medium plate, and evenly spread it with a disposable spreading rod. Spread the mixed solution in the other groups of EP tubes evenly on the plate, and mark each group of plates. After the mixed solution of each group is spread, place all the culture medium plates of each group upside down in an incubator at 35°C with 5% CO2 for 16 - 24 h. Take them out the next day, observe the growth status of the colonies in the control group to ensure that there is no contamination by miscellaneous bacteria, and observe the number of colonies growing in each group of plates. Use a high-definition mobile phone to take pictures of the colony growth status in each plate of each group, and record the number of colonies in each plate. The average value of the three groups is taken for the number of colonies in the control group. Calculate the fungal survival rate according to the following formula. The antibacterial effect is shown in Figures 6-10 , Figures 6-10 are the in vitro antibacterial effects of five gold complexes against Candida albicans standard strain (ATCC14053), Candida parapsilosis standard strain (ATCC 22019), Candida glabrata standard strain (ATCC MYA 2950), Candida krusei standard strain (ATCC 14243), and Candida tropicalis standard strain (ATCC 1369), respectively (1 - 5 in the picture represent AIE gold complexes 1 - 5). The five AIE gold complexes have significant inhibitory effects on the five Candida species within a concentration of 15 μM, and show obvious concentration dependence. The higher the concentration of the AIE gold complex, the stronger the antibacterial effect.

[0066] Experimental Example 3 CCK-8 cytotoxicity test: Subcultured cells (HACAT cells, C166 cells, LO2 cells, and L929 cells): The growth medium was prepared by mixing DMEM + 10% newborn bovine serum + double antibiotics in a ratio of 9:1:0.1. After cell resuscitation, the cell suspension + 10 ml of growth medium was added to a disposable sterile cell culture dish and incubated for 24 h to allow the cells to adhere and grow. When the cell distribution reached approximately 90%, the cells were digested, resuspended, and made into a cell suspension. After pipetting and mixing evenly, it was added to a disposable cell culture dish, and the number of cells was counted under a microscope. There were approximately 5000 cells per 100 μL. After pipetting and mixing the cell suspension evenly, 100 μL was added to a 96-well plate. After incubating for 24 h to allow the cells to adhere, the target AIE gold complex material was added. Different concentrations were set for each material, and 3 parallel wells were prepared for each concentration. After incubating in a 37 °C incubator for 30 min, the liquid in the wells was aspirated. 100 μl of PBS buffer was added to each well, and after pipetting and mixing evenly for 1 min, the liquid was aspirated. The PBS washing step was repeated 3 times. 10 μl of CCK-8 solution was added to each well, shaken well without generating bubbles, and incubated in the incubator for 2 h. 100 μl of PBS buffer was added to each well, shaken on a shaker for 1 min until the color was uniform, and the absorbance at 450 nm was measured using a microplate reader. The absorbance ratio was calculated using Origin 2022 software to evaluate the biocompatibility of the five AIE gold complexes, as shown in Figure 11 , in the concentration range of 0 to 25 μM (μmol / L), the cell survival rates of Materials 1, 2, 4, and 5 in all two cell lines exceeded 80%. 1-5 in the figure represent AIE gold complexes 1-5 respectively.

[0067] Experimental Example 4 Animal experiment: Establish a mouse model of fungal infection: Circular skin wound was created on the back of the mouse, and then the wound was covered with a suspension of Candida albicans. After growing for 48 h, the modeling was completed. Then, the mice with successfully infected fungal skin wounds were divided into three groups, including a PBS control group, a gold complex treatment group, and an antifungal drug treatment group, with 5 mice in each group. Different treatment regimens were implemented for each group of mice for three consecutive days, namely: AIE gold complex 1 prepared in Example 1, miconazole, and PBS, for a total of 3 treatments (on the 1st, 2nd, and 3rd days). Then, the skin infection wounds of the mice were photographed and recorded to obtain the healing situation, and the wound healing situation of the mice was calculated using ImageJ software to evaluate the effects of different treatment regimens, as shown in Figure 14 , compared with the control group, the wound healing rate of the mice treated with AIE gold complex 1 was significantly accelerated.

[0068] Experimental Example 5 Fluorescence imaging experiment: Add 5 μmol / L of each of the five AIE gold complexes to the prepared fungal suspension, shake well, incubate in a constant temperature water bath for 30 min, without washing, then take out and centrifuge for 5 min (3500 revolutions per minute). After centrifugation, transfer about 10 μL of the stained fungal solution at the bottom to a glass slide, cover with a coverslip, and under a confocal laser scanning microscope, use 488 nm laser to excite the gold complex to directly image the fungi, as shown in Figures 13-15 , AIE gold complexes 1-5 can all "light up" the cell bodies and nuclei of the five fungi well, and they show relatively high imaging depth and clarity in fungal imaging. 1-5 in the figure represent AIE gold complexes 1-5 respectively.

[0069] The above are only the preferred embodiments of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and refinements can be made, and these improvements and refinements should also be regarded as the protection scope of the present invention.

Claims

1. A class of gold complexes with aggregation-induced emission properties, characterized in that, The structural formula of the gold complex is as follows: 。 2. The preparation method of the gold complex according to claim 1, characterized in that, The synthetic routes of gold complexes 1-5 are as follows: ， ， ， ， 。 3. The preparation method according to claim 2, characterized in that, The preparation methods of gold complexes 1 and 2 are as follows: Under a nitrogen atmosphere, KPF6, 4, and the ligand raw material are mixed to obtain a mixture. Then, after vacuum pumping and nitrogen replacement, dry DCM and dry methanol are added, and the mixture is stirred at room temperature for 24 h. After the reaction is completed, the mixture is successively extracted, dried over anhydrous sodium sulfate, filtered, and evaporated to obtain a crude product; the crude product is recrystallized to obtain the target product; When the ligand raw material is PPh3, gold complex 1 is obtained; When the ligand raw material is PCy3, gold complex 2 is obtained.

4. The preparation method according to claim 3, wherein The molar ratio of KPF6, 4, and the ligand raw material is (2.8-3.2):(1.8-2.2):(1.8-2.2); The mass-volume ratio of the mixture, dry DCM, and dry methanol is (130-150) mg:(15-25) mL:(8-12) mL.

5. The preparation method according to claim 2, wherein The preparation method of gold complex 3 is as follows: Under a nitrogen atmosphere, potassium carbonate, 1d, and 3a are mixed to obtain a mixture, and then the mixture is stirred at room temperature for 24 h. After the reaction is completed, the mixture is successively extracted, dried over anhydrous sodium sulfate, filtered, and evaporated to obtain a crude product; the crude product is recrystallized to obtain the target product gold complex 3.

6. The preparation method according to claim 5, characterized in that, The molar ratio of potassium carbonate, 1d, and 3a is (0.8-1.2):(0.4-0.6):(0.4-0.6).

7. The preparation method according to claim 2, characterized in that, The preparation method of gold complex 4 is as follows: Under a nitrogen atmosphere, 1d and silver oxide are mixed to obtain a mixture. Then, after vacuum pumping and nitrogen replacement, degassed dichloromethane is added, and the mixture is stirred at room temperature in the dark for 48 h under nitrogen. Then, thiothene chloroaurate is added, and the mixture is continuously stirred at room temperature for 12 h. After the reaction is completed, the mixture is successively filtered, concentrated under reduced pressure, separated and purified, and then precipitated with dichloromethane / n-hexane to obtain the target product gold complex 4.

8. The preparation method according to claim 7, wherein The molar ratio of 1d, silver oxide, and thiothene chloroaurate is (13-18):(6-10):(13-18); The mass-volume ratio of the mixture and degassed dichloromethane is (95-105) mg:(18-22) mL.

9. The preparation method according to claim 1, characterized in that, The preparation method of gold complex 5 is as follows: Under a nitrogen atmosphere, 5b and silver oxide are mixed to obtain a mixture. Then, after vacuum pumping and nitrogen replacement, degassed methanol is added, and the mixture is stirred at room temperature in the dark for 48 h under nitrogen. Then, sodium chloride and thiothene chloroaurate are added, and the mixture is continuously stirred at room temperature for 12 h. After the reaction is completed, the mixture is successively filtered, concentrated under reduced pressure, separated and purified, and then precipitated with dichloromethane / n-hexane to obtain the target product; The molar ratio of 5b, silver oxide, sodium chloride, and thiothene chloroaurate is (13-16):(6-10):(13-16):(13-16); The mass-volume ratio of the mixture and degassed methanol is (95-105) mg:(25-35) mL.

10. The application of the gold complex according to claim 1 in the visualization of fungal infections and / or in drugs for treating fungal infections.

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