A nitrogen azole-based metal organic framework and a preparation method and application thereof

Abstract

The application discloses a kind of azole-based metal organic framework and its preparation method and application, preparation method includes: sodium azide, hydrazine hydrate, 4-imidazole formaldehyde, ferrous trifluoromethyl sulfonate are dissolved in methanol solution and are reacted;The reaction product is filtered, washed, dried, and azole-based organic ligand is obtained;Azole-based organic ligand and transition metal salt are reacted in the mixed solution of N, N-dimethylformamide and methanol or ethanol, and the reaction product is centrifuged, filtered, washed, and azole-based metal organic framework is obtained.In the application, azole-based metal organic framework has the characteristics of spontaneous generation of singlet oxygen, without active oxygen under light conditions, and the needle shape of azole-based metal organic framework material can produce physical puncture effect on bacteria, which can effectively cooperate with the singlet oxygen spontaneously generated to resist bacteria.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of antibacterial technology, and particularly relates to a nitrogen azole metal organic framework and a preparation method and application thereof. BACKGROUND

[0002] The Lancet report estimates that about 1.27 million people died from AMR bacteria in 2019, and AMR bacteria involves six major pathogens such as Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa. A recent report by the World Health Organization estimates that if not controlled, AMR-based infections could cause 350 million deaths.

[0003] Regarding the research and development of antibiotics, there has been no new class of clinical antibiotics in the past 40 years. What is worse, most pharmaceutical companies have significantly reduced their investment in the research and development of new antibiotics, and we are entering the "post-antibiotic" era. Although the World Health Organization and other health organizations and professionals have called on the public to reduce the abuse of antibiotics, academic research has increasingly focused on exploring alternatives to antibiotics in the past few years. In addition to antibiotics, some traditional antibacterial materials, including metal ions and their oxides, antimicrobial peptides and quaternary ammonium salt compounds, generally have the limitations of high biological toxicity, low safety, easy drug resistance, etc. Therefore, new sterilization methods based on metal ions, high temperature, free radicals, physical puncture and the synergistic effect of multiple mechanisms are attracting more and more attention.

[0004] The rapid development of nanotechnology provides a promising strategy to combat drug-resistant bacteria. Compared with traditional antibiotics, nanomaterials such as metal organic frameworks (MOFs) allow rational engineering design, such as size control, surface modification, crystal change and stimulus-responsive functionalization, to obtain unique interactions with bacterial cells, which often exhibit unique killing mechanisms and extraordinary antibacterial properties. The mechanisms of MOFs materials for antibacterial applications usually include release based on ligands or metal ions, metal ions as active sites for sterilization, MOFs as light / heat sensitive agents for sterilization, physical puncture and synergistic sterilization of multiple mechanisms. As for MOFs as light / heat sensitive agents for sterilization, it usually needs light and heat to provide energy to produce active oxygen (such as singlet oxygen, superoxide free radicals, hydroxyl free radicals, etc.), but there is no report on MOFs spontaneously generating singlet oxygen for application in the field of antibacterial. SUMMARY

[0005] The present application is directed to the above technical problems, and the purpose of the present application is to provide a nitrogen azole metal organic framework and a preparation method and application thereof, the needle-shaped appearance of the nitrogen azole metal organic framework can cause a physical puncture effect on bacteria, and the nitrogen azole metal organic framework material has the characteristics of spontaneously generating singlet oxygen, and can generate active oxygen without light, and can effectively cooperate with the physical puncture effect to resist bacteria.

[0006] In order to achieve the above-mentioned purpose, the present application adopts the following technical solutions:

[0007] A preparation method of a nitrogen azole metal organic framework, comprising:

[0008] S1: dissolving sodium azide, hydrazine hydrate, 4-imidazole formaldehyde and ferrous trifluoromethyl sulfonate in a methanol solution for reaction; filtering, washing and drying the reaction product to obtain a nitrogen azole organic ligand;

[0009] S2: reacting the nitrogen azole organic ligand and a transition metal salt in a mixed solution of N,N-dimethylformamide and methanol or ethanol; centrifuging, filtering and washing the reaction product to obtain a nitrogen azole metal organic framework.

[0010] Further, the transition metal in the transition metal salt is any one of Mn, Fe, Cu, Co, Zn and Cd.

[0011] Further, the nitrogen azole metal organic framework is prepared by a solvothermal method in step S2, specifically including: dissolving the nitrogen azole ligand and the transition metal salt in a mixed solution of N,N-dimethylformamide and methanol or ethanol, reacting at 110-120 DEG C for 3-5 days, and then cooling to room temperature to obtain the nitrogen azole metal organic framework.

[0012] Further, the molar ratio of the nitrogen azole organic ligand to the transition metal salt in step S2 is 1:1-1.5.

[0013] Further, step S1 specifically includes:

[0014] The sodium azide and 4-imidazole formaldehyde are mixed and added to the methanol solution, and are dissolved by ultrasonic for 20-30 minutes;

[0015] The hydrazine hydrate is added to the methanol solution and uniformly mixed;

[0016] The ferrous trifluoromethyl sulfonate is added to the methanol solution, and the ferrous trifluoromethyl sulfonate is a catalyst; under the action of the catalyst, the sodium azide, the 4-imidazole formaldehyde and the hydrazine hydrate in the methanol solution react to obtain a nitrogen azole organic ligand, and the nitrogen azole organic ligand is (N-[5-(1H-imidazole-4-yl)-tetrazole]-C-(1H-imidazole-4-yl) methylamine).

[0017] Further, the molar ratio of sodium azide, hydrazine hydrate, 4-imidazole formaldehyde and ferrous trifluoromethyl sulfonate is 1:1:0.5-2:0.5-2, the reaction temperature of step S1 is 50-70 DEG C, and the reaction time is 24-48 hours.

[0018] The application also provides a nitrogen azole metal organic framework prepared based on the preparation method.

[0019] The application of the nitrogen azole metal organic framework as described above in the preparation of an antibacterial product.

[0020] Further, the antibacterial product includes an anti-E. coli product, an anti-S. aureus product, an anti-P. aeruginosa product and other anti-Gram-positive and Gram-negative bacteria products.

[0021] Further, the nitrogen azole metal organic framework is used for the preparation of an antibacterial product after sterilization under the irradiation of an ultraviolet lamp.

[0022] Compared with the prior art, the application has the advantages that the preparation method of the nitrogen azole metal organic framework is simple, environmentally friendly and high in efficiency, and is suitable for large-scale preparation.

[0023] The nitrogen azole metal organic framework has the advantages of high specific surface area, adjustable pore size and surface modification, and is stable in structure and can exist stably in most organic solvents; compared with traditional metal oxides, the nitrogen azole metal organic framework has lower biological toxicity; compared with antibiotics and quaternary ammonium salt antibacterial agents, the nitrogen azole metal organic framework basically does not produce bacterial resistance; and the cost of the nitrogen azole metal organic framework is much lower than that of an antibacterial peptide antibacterial agent.

[0024] The needle-shaped shape of the nitrogen azole metal organic framework can produce a physical puncture effect on bacteria, and the nitrogen azole metal organic framework material has the characteristics of spontaneously generating singlet oxygen, and can produce reactive oxygen without light, which can effectively cooperate with the physical puncture effect to resist bacteria; the nitrogen azole metal organic framework has excellent performance in resisting E. coli, S. aureus and P. aeruginosa. BRIEF DESCRIPTION OF DRAWINGS

[0025] The drawings incorporated into the specification and constituting a part of the specification show embodiments consistent with the application and, together with the specification, serve to explain the principles of the application.

[0026] In order to more clearly illustrate the technical solutions in the embodiments of the application or the prior art, the drawings needed to be used in the embodiments or the prior art description will be briefly introduced as follows, and obviously, other drawings can also be obtained by those skilled in the art without creative labor.

[0027] In the drawings:

[0028] Figure 1 The synthetic route and antibacterial mechanism of azole-based metal organic frameworks;

[0029] Figure 2 For ligand 1 H-NMR;

[0030] Figure 3 For ligand 13 C-NMR;

[0031] Figure 4 Comparison of diffraction peaks between simulated and experimental powders of nitrogen-based metal-organic frameworks;

[0032] Figure 5 This is the thermogravimetric analysis diagram of the nitrogen-based azole metal-organic framework;

[0033] Figure 6 To test the solvent stability of azole-based metal-organic frameworks;

[0034] Figure 7 The crystal structure and stacking mode of nitrogen-based azole metal organic framework;

[0035] Figure 8 is the BET surface area and pore size distribution of the nitrogen azole-based metal organic framework;

[0036] Figure 9 To characterize the morphology of nitrogen-based metal-organic frameworks;

[0037] Figure 10 Schematic diagram of the coating of azole-based metal organic framework against Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa;

[0038] Figure 11 Bacterial morphology analysis of azole-based metal organic frameworks against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa;

[0039] Figure 12 Bacterial live-death assays after the azole-based metal-organic frameworks were used to detect Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa;

[0040] Figure 13 The spontaneous generation of singlet oxygen ( 1 O2) EPR test;

[0041] Figure 14 The spontaneous generation of singlet oxygen ( 1 O2) verification experiment diagram. DETAILED DESCRIPTION

[0042] The following examples are used to illustrate the present application, but are not used to limit the scope of the present application. Modifications or replacements of the method, steps or conditions of the present application are all within the scope of the present application without departing from the spirit and essence of the present application. If not specifically indicated, the experimental materials, reagents, instruments and the like used in the examples of the present application can be commercially available; if not specifically indicated, all technical means in the examples of the present application are conventional means known to those skilled in the art.

[0043] The application provides a preparation method of a nitrogen azole-based metal organic framework, comprising:

[0044] S1: dissolving sodium azide, hydrazine hydrate, 4-imidazole formaldehyde and ferrous trifluoromethyl sulfonate in a methanol solution to react; filtering, washing and drying the reaction product to obtain a nitrogen azole-based organic ligand.

[0045] Specifically, the method comprises the following steps:

[0046] S11: mixing sodium azide and 4-imidazole formaldehyde and adding them to a methanol solution, and dissolving for 20-30 minutes under ultrasonic;

[0047] S12: adding hydrazine hydrate to the methanol solution and uniformly mixing;

[0048] S13: adding ferrous trifluoromethyl sulfonate to the methanol solution, wherein the ferrous trifluoromethyl sulfonate is a catalyst, and under the action of the catalyst, the sodium azide, 4-imidazole formaldehyde and hydrazine hydrate in the methanol solution react to obtain a nitrogen azole-based organic ligand TITM, and the nitrogen azole-based organic ligand TITM is specifically (N-[5-(1H-imidazole-4-yl)-tetrazole]-C-(1H-imidazole-4-yl)methylamine).

[0049] In the preparation of the nitrogen azole-based organic ligand, the molar ratio of sodium azide, hydrazine hydrate, 4-imidazole formaldehyde and ferrous trifluoromethyl sulfonate is 1:1:0.5-2:0.5-2. The reaction temperature in step S13 is 50-70°C, and the reaction time is 24-48 hours.

[0050] S2: reacting the nitrogen azole-based organic ligand and a transition metal salt in a mixed solution of N,N-dimethylformamide and methanol or ethanol, and centrifuging, filtering and washing the reaction product to obtain a nitrogen azole-based metal organic framework. The transition metal in the transition metal salt is any one of Mn, Fe, Cu, Co, Zn and Cd.

[0051] Specifically, the nitrogen azole-based metal organic framework can be prepared by a solvothermal method, specifically comprising: dissolving the nitrogen azole-based ligand and the transition metal salt in a mixed solution of N,N-dimethylformamide and methanol or ethanol, reacting at 110-120°C for 3-5 days, and then cooling to room temperature to obtain the nitrogen azole-based metal organic framework.

[0052] The molar ratio of the azole-based organic ligand to the transition metal salt is 1:1 to 1.5. When calculating the molar ratio of the azole-based organic ligand to the transition metal salt, the molar content of the transition metal salt shall prevail.

[0053] Example 1

[0054] This embodiment provides a method for preparing an azole-based metal organic framework, comprising:

[0055] S11: Weigh 4 mmol of 4-imidazolecarboxaldehyde and 5 mmol of NaN3, add methanol to dissolve; sonicate for 20 to 30 minutes to dissolve;

[0056] S12: Pipette 4 mmol of hydrazine hydrate solution, add the above methanol solution, and mix evenly;

[0057] S13: Add 4 mmol of ferrous trifluoromethanesulfonate to the methanol solution and mix evenly. Use ferrous trifluoromethanesulfonate as a catalyst, place the reaction solution at 60°C for condensation reflux reaction for 24 to 48 hours, and you can get a lotus pink-colored azole-based organic ligand TITM. The azole-based organic ligand TITM is specifically (N-[5-(1H-imidazole-4-yl)-tetrazole]-C-(1H-imidazole-4-yl)methylamine ligand TITM; the yield is 60% (based on 4-imidazolecarboxaldehyde).

[0058] The synthetic route of nitrogen azole organic ligands is as follows Figure 1 , the prepared nitrogen azole organic ligand 1 H-NMR diagram, such as Figure 2 As shown, the ligand contains four groups of hydrogen, and the corresponding positions are: 1 H-NMR (400 MHz, Methanol-d4, 298 K): Chemical shift of H group 1: δ (ppm) 9.16 (s, 1H), chemical shift of H group 2: 8.04 (d, 1H), chemical shift of H group 3: 7.75 (s, 1H), chemical shift of H group 4: 7.67-7.52 (m, 2H). H group 1 is the H at the double bond, totaling 1 H atom; H ​​group 2 is the H directly attached to the tetrazole, totaling 1 H atom; H ​​group 3 is the H directly attached to the double bond, totaling 1 H atom; H ​​group 4 is the H not attached to other groups in the two imidazole groups, totaling 2 H atoms. The ratio of the number of H atoms in these four groups is 1:1:1:2.

[0059] Nitrogen azole organic ligand 13 C-NMR diagram, such as Figure 3 As shown, 13C-NMR (400 MHz, Methanol-d4, 298 K): δ 152.29 (1st C atom), 148.60 (2nd C atom), 147.45 (3rd C atom), 146.51 (4th C atom), 137.87 (5th C atom), 133.67 (6th C atom), 131.83 (7th C atom), 122.93 (8th C atom), corresponding to the C atom positions identified by the ligand.

[0060] S2: about 0.04 mmol of azole-based organic ligand and 0.05 mmol of transition metal (M = Mn, Fe, Cu, Co, Zn, Cd, etc., taking Mn as an example for analysis) salt are weighed into a mixed solution of N, N-dimethylformamide and ethanol (about 3 mL, 1:4, v / v), and placed in a 10 mm inner diameter hard glass tube, and sealed with a hydrogen flame. 110-120 °C for 3-5 days, and then reduced to room temperature at a rate of 5 °C per hour, and finally yellow needle-like crystals are obtained, which are then washed with acetone three times to obtain azole-based metal organic framework.

[0061] As shown in Figure 4 , it is a comparison of azole-based metal organic framework simulated powder and powder diffraction peaks in Example 1, from Figure 4 it can be seen that the structure of the framework material synthesized by experiment is consistent with the structure simulated by single crystal.

[0062] As shown in Figure 5 , it is a thermogravimetric analysis diagram of the azole-based metal organic framework in Example 1, from Figure 5 it can be seen that the weight loss of 40-90 °C is mainly concentrated in the loss of solvent molecules in the framework, and the framework tends to be stable at 90-300 °C, and only after 300 °C, the framework appears metastable; fully demonstrating that the framework has good thermal stability.

[0063] As shown in Figure 6 , it is a solvent stability test of the azole-based metal organic framework in Example 1, from Figure 6 it can be seen that the azole-based metal organic framework can exist stably in acetonitrile MeCN, ethanol EtOH, methanol MeOH, N, N-dimethylformamide DMF, water and air, fully demonstrating that the framework has good solvent stability.

[0064] As shown in Figure 7 , it is the crystal structure and packing method of the azole-based metal organic framework in Example 1, from Figure 7 it can be seen that the framework material is a 3D structure synthesized by self-assembly of azole-based organic ligand TITM and transition metal (M = Mn, Fe, Cu, Co, Zn, Cd, etc., taking Mn as an example for analysis) salt, and the framework has a long ordered structure and clear visible channels.

[0065] As shown in Figure 1, the BET surface area and pore size distribution of the azole-based metal organic framework in Example 1 can be seen from Figure 1. Figure 8 Figure 8 As shown in Figure 1, the azole-based metal organic framework has a high BET specific surface area of about 721 cm 2 / g, and a regular pore size distribution of about 0.5 nm.

[0066] As shown in Figure 2, the morphology characterization of the azole-based metal organic framework in Example 1 can be seen from Figure 2. Figure 9 Figure 9 As shown in Figure 2, the azole-based metal organic framework material has a needle-like morphology, which has a very good physical piercing effect on bacteria.

[0067] Example 2

[0068] The preparation method of the azole-based metal organic framework provided in this embodiment comprises:

[0069] S11: 4 mmol of 4-imidazole formaldehyde and 5 mmol of NaN3 are weighed and dissolved in methanol; ultrasonic dissolution is performed for 20-30 minutes;

[0070] S12: 5 mmol of hydrazine hydrate solution is removed and added to the above methanol solution and uniformly mixed;

[0071] S13: 4 mmol of ferrous trifluoromethyl sulfonate is added to the methanol solution and uniformly mixed, the ferrous trifluoromethyl sulfonate is a catalyst, and the reaction liquid is placed in a 50℃ condensation reflux reactor for 24-48 hours to obtain a pink azole-based organic ligand TITM, the azole-based organic ligand TITM is specifically (N-[5-(1H-imidazole-4-yl)-tetrazole]-C-(1H-imidazole-4-yl) methylamine ligand TITM; the yield is 60% (based on 4-imidazole formaldehyde).

[0072] S2: about 0.05 mmol of azole-based organic ligand and 0.075 mmol of transition metal (M=Mn, Fe, Cu, Co, Zn, Cd, etc., taking Fe as an example for analysis) salt are dissolved in a mixed solution of N, N-dimethylformamide and ethanol (about 3 mL, 1:4, v / v) and placed in a 10 mm inner diameter hard glass tube, which is sealed with a hydrogen flame. 110℃-120℃ reaction for 3-5 days, and reduce to room temperature at a speed of 3℃ per hour, finally get yellow needle-like crystals, then washed with acetone three times, to obtain azole-based metal organic framework.

[0073] Example 3

[0074] The preparation method of the azole-based metal organic framework provided in this embodiment comprises: ​​

[0075] S11: weigh 8 mmol of 4-imidazole carboxaldehyde, 4 mmol of NaN3, and dissolve in methanol; ultrasonic for 20-30 minutes for dissolution;

[0076] S12: further take 4 mmol of hydrazine hydrate solution, add to the above methanol solution, and mix uniformly;

[0077] S13: add 8 mmol of ferrous triflate to the methanol solution, mix uniformly, and the ferrous triflate is a catalyst; place the reaction liquid in a 70°C condensation reflux reaction for 24-48 hours, and obtain a pink nitrogen azole organic ligand TITM; the nitrogen azole organic ligand TITM is specifically (N-[5-(1H-imidazole-4-yl)-tetrazole]-C-(1H-imidazole-4-yl)methylamine ligand TITM; the yield is 60% (based on 4-imidazole carboxaldehyde).

[0078] S2: weigh about 0.05 mmol of the nitrogen azole organic ligand and 0.075 mmol of a transition metal (M=Mn, Fe, Cu, Co, Zn, Cd, etc., take Cd as an example for analysis) salt in a mixed solution of N,N-dimethylformamide and ethanol (about 3 mL, 1:4, v / v), and place in a 10 mm inner diameter hard glass tube, and seal the tube with a hydrogen flame. React at 110°C-120°C for 3-5 days, and reduce to room temperature at a rate of 5°C per hour, and finally obtain yellow needle-shaped crystals, and then wash with acetone three times, and obtain the nitrogen azole metal organic framework.

[0079] Experimental Example 4

[0080] Application of the nitrogen azole metal organic framework in preparation of an antibacterial product. The antibacterial product in this embodiment can be a liquid bactericide, etc.

[0081] Preparation of the MOF bactericide: prepare a bactericide with a concentration of 0.5-2 mg / L of the nitrogen azole metal organic framework, that is, weigh about 0.5-2 mg of the nitrogen azole metal organic framework in Example 1, and add to about 1 mL of a phosphate buffered saline solution (PBS, pH=7.4) and irradiate under a UV lamp for about 1-2 hours. The role of the UV lamp irradiation is to sterilize the nitrogen azole metal organic framework.

[0082] Preparation of a blank group bactericide, which only contains 1 mL of a phosphate buffered saline solution (PBS, pH=7.4) and is irradiated under a UV lamp for about 1-2 hours.

[0083] Preparation of a bacterial solution: dilute E. coli, S. aureus, and P. aeruginosa with a concentration of 10 9 CFU / mL to 10 5CFU / mL, the diluted E. coli bacteria solution, the Staphylococcus aureus bacteria solution, the Pseudomonas aeruginosa bacteria solution.

[0084] Antibacterial test:

[0085] The diluted bacteria solution was co-cultured with the MOF bactericide and the blank group bactericide at 37°C for 1-2 hours. For E. coli, three groups of MOF bactericides with different concentrations and the same blank group bactericide were set, and the concentrations of the three groups of MOF bactericides were 0.5 mg / mL, 1 mg / mL and 2 mg / mL, respectively. For Staphylococcus aureus, three groups of MOF bactericides with different concentrations and the same blank group bactericide were set, and the concentrations of the three groups of MOF bactericides were 0.5 mg / mL, 1 mg / mL and 2 mg / mL, respectively. For Pseudomonas aeruginosa, three groups of MOF bactericides with different concentrations and the same blank group bactericide were set, and the concentrations of the three groups of MOF bactericides were 0.5 mg / mL, 1 mg / mL and 2 mg / mL, respectively.

[0086] As shown in FIG. 1, it is a schematic diagram of the plate coating after co-culturing different bactericides with E. coli, Staphylococcus aureus and Pseudomonas aeruginosa. It can be seen that, compared with the number of colonies in the blank group bactericide, the number of colonies of E. coli, Staphylococcus aureus and Pseudomonas aeruginosa after adding different concentrations of MOF bactericide in the three groups of experiments is obviously less, which shows that the MOF bactericide in the present application has certain anti-E. coli, Staphylococcus aureus and Pseudomonas aeruginosa performance. Figure 10

[0087] For E. coli, Staphylococcus aureus and Pseudomonas aeruginosa, 50-100 μL of the bacteria solution co-cultured with 2 mg / mL MOF bactericide and blank group bactericide was uniformly dispersed on a nutrient agar plate, and the dispersed bacteria solution was placed in a 37°C incubator for 8-12 hours of culture. After the culture was completed, the cell morphology of the colonies was observed, and the live and dead detection of the colonies was performed.

[0088] As shown in FIG. 2, it is the bacterial morphology after adding 2 mg / mL MOF bactericide and blank group bactericide for culture. It can be seen that, after co-culturing the three kinds of bacteria with the MOF bactericide, the bacterial surface morphology appears obvious piercing and shrinkage, while the cell morphology after co-culturing with the blank group bactericide does not appear obvious piercing and shrinkage; which fully shows that the MOF bactericide has certain antibacterial effect. Figure 11

[0089] As shown in FIG. 3, it is a schematic diagram of the plate coating after co-culturing different bactericides with E. coli, Staphylococcus aureus and Pseudomonas aeruginosa. It can be seen that, compared with the number of colonies in the blank group bactericide, the number of colonies of E. coli, Staphylococcus aureus and Pseudomonas aeruginosa after adding different concentrations of MOF bactericide in the three groups of experiments is obviously less, which shows that the MOF bactericide in the present application has certain anti-E. coli, Staphylococcus aureus and Pseudomonas aeruginosa performance. Figure 12 ​​The figure shows the cell live-death detection analysis after adding 2 mg / mL MOF fungicide and blank fungicide. Through laser confocal microscopy, it can be clearly observed that more bacteria died (red area) after MOF fungicide culture than blank fungicide culture, which also shows that the framework has a certain antibacterial effect.

[0090] Example 5

[0091] The azole-based metal organic framework prepared in this application has a needle-like shape, which can produce a physical puncture effect on bacteria. At the same time, the azole-based metal organic framework material prepared in this application has the ability to spontaneously generate singlet oxygen ( 1 O2) can generate active oxygen, namely singlet oxygen ( 1 O2), which can effectively cooperate with the physical puncture effect to fight bacteria.

[0092] In this example, the singlet oxygen generated by the azole-based metal-organic framework was detected by an electroparamagnetic resonance spectrometer (EPR), and the singlet oxygen generated was further verified by various reagents such as 1,3-diphenylisobenzofuran (DPBF) and 3,3',5,5'-tetramethylbenzidine (TMB).

[0093] The azole-based metal organic framework Mn (TITM) prepared in Example 1 was used as the experimental group. 1 mg of the Mn (TITM) prepared in Example 1 was mixed uniformly with 1 mL of methanol solution by ultrasonication for 30 to 60 minutes. Without illumination, the capture agent 2,2',6,6'-tetramethylpiperidine (TEMP) was directly added to obtain the experimental group. An equal amount of the capture agent 2,2',6,6'-tetramethylpiperidine (TEMP) was directly added to 1 mL of methanol solution to obtain the control group. Figure 13 As shown, the nitrogen-based metal organic framework spontaneously generates singlet oxygen ( 1 From the EPR test spectrum of O2), it can be seen that compared with the control group, the experimental group can produce three obvious signal peaks, which are singlet oxygen signal peaks, indicating that the material can spontaneously generate singlet oxygen.

[0094] like Figure 14 As shown, the nitrogen-based metal organic framework spontaneously generates singlet oxygen ( 1 O2) verification experiment: Figure 14 (a) UV absorption spectrum of singlet oxygen captured using 1,3-diphenylisobenzofuran (DPBF) as a blank control group; Figure 14 (b) UV absorption spectrum of singlet oxygen captured by 1,3-diphenylisobenzofuran (DPBF)-based azole-based metal-organic framework (Mn(ITIM)-MOF); Figure 14(c) Comparison of the UV absorption spectra of 1,3-diphenylisobenzofuran (DPBF) capturing singlet oxygen before and after incorporation into the azole-based metal-organic framework. Figure 14 (d) UV absorption spectrum of singlet oxygen captured using 3,3',5,5'-tetramethylbenzidine (TMB) as a blank control group; Figure 14 (e) UV absorption spectrum of singlet oxygen captured by 3,3',5,5'-tetramethylbenzidine (TMB)-based azole metal-organic framework (Mn(ITIM)-MOF); Figure 14 (f) Comparison of the UV absorption spectra of singlet oxygen captured by 3,3',5,5'-tetramethylbenzidine (TMB) before and after its addition to the azole-based metal-organic framework.

[0095] ​ It can be seen that compared with pure DPBF solution, the singlet oxygen generated by the addition of the azole-based metal-organic framework can degrade DPBF faster, producing a UV absorption peak at 415nm. As time goes by, the absorption peak gradually decreases and the color of the solution gradually becomes lighter. In addition, compared with pure TMB, the singlet oxygen generated by the addition of the azole-based metal-organic framework can oxidize TMB faster, producing a UV absorption peak at 652nm. As time goes by, the absorption peak gradually increases and the color of the solution gradually deepens. The above verification experiments further demonstrate that the azole-based metal-organic framework material has the ability to generate singlet oxygen.

[0096] Compared with other traditional antibacterial materials, the azole-based metal organic framework prepared in the present invention has the advantages of high specific surface area, adjustable pore size, and surface modifiability. In addition, its structure is stable and it can exist stably in most organic solvents.

[0097] Compared with traditional metal oxides, the azole-based metal organic framework of the present application has lower biological toxicity; compared with antibiotics and quaternary ammonium salt antibacterial agents, it basically does not produce bacterial resistance; and its cost is much lower than antibacterial agents such as antimicrobial peptides.

[0098] The azole-based metal organic framework of the present invention has a needle-like shape, which can produce a physical puncture effect on bacteria, and the azole-based metal organic framework material prepared by the present invention has the ability to spontaneously generate singlet oxygen ( 1 O2) can generate active oxygen, namely singlet oxygen ( 1 O2), which can effectively cooperate with the physical puncture effect to fight bacteria.

[0099] It can be understood that the above embodiments only express the preferred embodiments of the present application, the description is more specific and detailed, but it cannot be understood as the limitation of the patent scope of the present application; it should be pointed out that for ordinary skilled in the art, the above technical features can be freely combined without departing from the concept of the present application, and several modifications and improvements can be made, which belong to the protection scope of the present application; therefore, any equivalent transformation and modification made with the patent claim scope of the present application shall belong to the coverage of the patent claim of the present application.

Claims

1. An application of an azole-based metal organic framework in the preparation of an antibacterial product, characterized in that: The preparation method of the azole-based metal organic framework comprises: S1: dissolving sodium azide, hydrazine hydrate, 4-imidazolecarboxaldehyde, and ferrous trifluoromethanesulfonate in a methanol solution to react; filtering, washing, and drying the reaction product to obtain an azole-based organic ligand; S2: reacting an oxazolidinone organic ligand and a transition metal salt in a mixed solution of N,N-dimethylformamide and methanol or ethanol, centrifuging, filtering, and washing the reaction product to obtain an oxazolidinone metal organic framework.

2. An application according to claim 1, characterized in that: The transition metal in the transition metal salt is any one of Mn, Fe, Cu, Co, Zn and Cd.

3. The application according to claim 1, characterized in that: Step S2 uses a solvothermal method to prepare an oxazolyl metal organic framework, specifically comprising: dissolving an oxazolyl ligand and a transition metal salt in a mixed solution of N,N-dimethylformamide and methanol or ethanol, reacting at 110°C to 120°C for 3 to 5 days, and cooling to room temperature to obtain an oxazolyl metal organic framework.

4. The application according to claim 1, characterized in that: In step S2, the molar ratio of the azole-based organic ligand to the transition metal salt is 1:1 to 1.

5.

5. The use according to claim 1, characterized in that: Step S1 specifically includes: Sodium azide and 4-imidazole carboxaldehyde were mixed and added to the methanol solution, and sonicated for 20 to 30 minutes to dissolve; Add hydrazine hydrate to the methanol solution and mix evenly; Ferrous trifluoromethanesulfonate is added to a methanol solution, wherein the ferrous trifluoromethanesulfonate serves as a catalyst. Under the action of the catalyst, sodium azide, 4-imidazolecarboxaldehyde and hydrazine hydrate in the methanol solution react to obtain an oxazolyl organic ligand, wherein the oxazolyl organic ligand is (N-[5-(1H-imidazole-4-yl)-tetrazole]-C-(1H-imidazole-4-yl)methylamine).

6. A use according to claim 5, characterized in that: The molar ratio of sodium azide, hydrazine hydrate, 4-imidazolecarboxaldehyde and ferrous trifluoromethanesulfonate is 1:1:0.5-2:0.5-2. The reaction temperature of step S1 is 50-70° C. and the reaction time is 24-48 hours.

7. The use according to claim 1, wherein the antibacterial product comprises a product against Gram-positive bacteria and Gram-negative bacteria.

8. The use according to claim 1, wherein the azole-based metal organic framework is sterilized under ultraviolet light and then used in the preparation of antibacterial products.

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