A metal-organic framework-derived antibacterial nanomaterial, its preparation method and application

Abstract

This invention relates to a metal-organic framework (MOF)-derived antibacterial nanomaterial, its preparation method, and its applications. Nano-UiO-66-NH2 was synthesized via a solvothermal method, and then, under the catalysis of copper chloride, nano-UiO-66-Pyrrole was successfully synthesized from UiO-66-NH2 and 2,5-dimethoxytetrahydrofuran. This MOF-derived antibacterial material has a simple synthesis method, readily available raw materials, high stability, and excellent antibacterial properties, expanding the application range of MOFs and their derivatives. Beneficial effects: The research on constructing MOF-derived materials and their antibacterial properties through post-modification in this invention has not been reported in the literature. The preparation method is simple, with high yield, good thermal stability, and excellent antibacterial activity, indicating that the designed antibacterial material has the potential for application in the fields of biomedicine and food safety.

Description

Technical Field

[0001] This invention belongs to the field of antibacterial materials technology, specifically relating to a metal-organic framework-derived nano-antibacterial material. Background Technology

[0002] In recent years, bacteria have become a major cause of health problems, posing a serious threat to public safety worldwide. Despite the continuous invention and discovery of numerous bactericides such as antibiotics and disinfectants, providing many effective methods for killing bacteria, the improper use of antibiotics has led to the continuous development of antibiotic resistance. The emergence of multidrug-resistant bacteria (MDRs) in recent years has undoubtedly sounded an alarm for humanity, posing a significant threat to global public health. Metal-organic frameworks (MOFs) are an important class of compounds in which organic bridging ligands connect metal ions or metal clusters (secondary building blocks, SBUs), forming a three-dimensional coordination network with potential porosity. As a crystalline porous material, MOFs are increasingly interacting with biomolecules, showing great promise in areas such as biopharmaceutical delivery and antibacterial applications. The antibacterial mechanisms of MOFs can be categorized into four types: 1. Physical contact; 2. Release of small organic molecules, metal ions, and ligands; 3. Oxidative stress; 4. Photothermal effect. MOFs interact with bacteria through physical contact via van der Waals interactions, electrostatic interactions, and hydrophobic interactions, leading to membrane disruption, inactivation of key cellular components, and ultimately bacterial death. This sterilization method is unaffected by bacterial drug resistance. Furthermore, MOFs can also achieve sustained bactericidal effects through the release of antibacterial small molecules not inherent to the framework itself.

[0003] To date, there have been no reports on the use of MOF-derived nanomaterials for antibacterial properties by modifying pyrrole into MOF frameworks through post-modification.

[0004] Chinese patent application CN115785475A discloses an antibacterial metal-organic framework material, its preparation method, and its application. The method involves providing solutions of ferric nitrate, dimethylimidazole, and zinc nitrate in molar percentages; mixing the three solutions; reacting them under an inert gas atmosphere; and centrifuging and washing to remove excess metal ions and ligand molecules after the reaction to obtain the antibacterial metal-organic framework material. The iron-doped metal-organic framework material prepared by this patent exhibits antibacterial activity in a bacterial environment containing hydrogen peroxide, undergoing a Fenton reaction to generate a large number of active hydroxyl radicals. It can also mitigate the toxicity and drug resistance caused by the use of organic compounds such as antibacterial drugs and antibiotics. However, the preparation process of this patented antibacterial material is complex, and its antibacterial activity is relatively poor; therefore, further improvements are needed. Summary of the Invention

[0005] The technical problem to be solved by this invention is how to integrate physical contact sterilization and organic small molecule sterilization into a cheap and readily available material to achieve spectral, efficient and long-lasting antibacterial properties.

[0006] The present invention solves the above-mentioned technical problems through the following technical means:

[0007] The first aspect of the present invention provides a method for the large-scale preparation of nano-UiO-66-NH2, comprising the following steps: placing zirconium tetrachloride (ZrCl4), 2-aminoterephthalic acid (NH2-H2BDC) and benzoic acid in a reaction vessel, heating and reacting to obtain off-white nano-UiO-66-NH2 with a main particle size of 50 nm.

[0008] Beneficial effects: The UiO-66-NH2 of this invention is a nanomaterial with a main particle size of 50 nm, which can be prepared in large quantities. The ligand is derived from 2-aminoterephthalic acid, and the metal is derived from ZrCl4. Its synthesis method is simple, the raw materials are readily available, and it has high stability.

[0009] Preferably, the mass ratio of ZrCl4, NH2-H2BDC and benzoic acid is (2-4):(1-3):(55-65).

[0010] Preferably, the mass ratio of ZrCl4,NH2-H2BDC and benzoic acid is 3:2:60.

[0011] Preferably, the reaction conditions are 100-140℃ for 20-28h.

[0012] Preferably, the washing process involves washing three times each with N,N-dimethylformamide (DMF) and methanol.

[0013] The second aspect of this invention provides a post-modification preparation method for derived nano-UiO-66-Pyrrole, comprising the following steps: weighing a certain amount of UiO-66-NH2 and 2,5-dimethoxytetrahydrofuran, dissolving them in deionized water, adding CuCl2 as a catalyst, and heating the reaction to obtain derived nano-UiO-66-Pyrrole with a main particle size of 50 nm. (The synthesized material is characterized by powder diffraction, infrared spectroscopy, scanning electron microscopy, N2 adsorption / desorption, thermogravimetric analysis, and UV-Vis absorption spectroscopy as the target product.)

[0014] Beneficial effects: The derived nanomaterial of this invention is UiO-66-Pyrrole, with a morphology similar to UiO-66-NH2 and a size of 50 nm. The ligand is derived from 2-aminoterephthalic acid, the metal from ZrCl4, the derivatized unit from 2,5-dimethoxytetrahydrofuran, and the pyrrole ring from post-modification. Its synthesis method is simple, the raw materials are readily available, and it exhibits high stability.

[0015] Preferably, the molar ratio of UiO-66-NH2 to 2,5-dimethoxytetrahydrofuran is 1:4-8.

[0016] Preferably, the molar ratio of UiO-66-NH2 to 2,5-dimethoxytetrahydrofuran is 1:6.

[0017] Preferably, UiO-66-NH2 and 2,5-dimethoxytetrahydrofuran are dissolved in deionized water and then dispersed using ultrasound.

[0018] Preferably, the reaction is carried out under nitrogen atmosphere with reflux at 80°C and stirring for 12 hours.

[0019] Preferably, the washing process specifically involves washing three times with deionized water and CHCl3 respectively.

[0020] Preferably, the drying temperature is 60°C and the drying time is 12 hours.

[0021] A third aspect of the present invention proposes the application of the metal-organic framework-derived material UiO-66-Pyrrole prepared by the above preparation method as an antibacterial material.

[0022] Beneficial effects: UiO-66-Pyrrole has good antibacterial activity against Escherichia coli (Gram-negative bacteria). At a concentration of 5 mg / mL, the OD value of the bacterial solution decreased from the initial 1.735-1.78 to 0.045-0.055.

[0023] Preferably, the antibacterial application is based on Escherichia coli (a Gram-negative bacterium).

[0024] Preferably, the concentration of the antibacterial agent is 5 mg / mL.

[0025] Preferably, the OD value of the bacterial solution is reduced from the initial 1.735-1.78 to 0.045-0.055.

[0026] The advantages of this invention are:

[0027] 1. This invention provides a method for the large-scale preparation of nano-UiO-66-NH2. This method is simple to prepare, the raw materials are readily available and inexpensive, and it can be mass-produced.

[0028] 2. This invention proposes a post-modification preparation method for derived nano-UiO-66-Pyrrole. This method is simple to operate, can maintain the morphology and size of the parent UiO-66-NH2, and enhances thermal stability.

[0029] 3. This invention proposes an antibacterial material, its preparation method, and its application. This type of antibacterial material has the advantages of both physical contact sterilization and organic small molecule sterilization, and has not been reported in the literature to date. Attached Figure Description

[0030] Figure 1 These are powder diffraction patterns of the UiO-66-NH2 and UiO-66-Pyrrole materials prepared in Example 1 of this invention;

[0031] Figure 2 These are the infrared spectra of the UiO-66-NH2 and UiO-66-Pyrrole materials prepared in Example 1 of this invention;

[0032] Figure 3 These are scanning electron microscope images of the UiO-66-NH2 and UiO-66-Pyrrole materials prepared in Example 1 of this invention;

[0033] Figure 4 This is the N2 adsorption / desorption diagram of the UiO-66-NH2 and UiO-66-Pyrrole materials prepared in Example 1 of this invention;

[0034] Figure 5 These are thermogravimetric diagrams of the UiO-66-NH2 and UiO-66-Pyrrole materials prepared in Example 1 of this invention;

[0035] Figure 6 This is the UV-Vis absorption spectrum of the UiO-66-NH2 and UiO-66-Pyrrole materials prepared in Example 1 of this invention;

[0036] Figure 7 This describes the post-modification reaction mechanism of the UiO-66-Pyrrole material prepared in Example 1 of this invention;

[0037] Figure 8 This is a diagram showing the bactericidal effect of UiO-66-Pyrrole prepared in Example 1 of this invention and its reference material;

[0038] Figure 9 This is a comparison chart of the bactericidal effects of the UiO-66-Pyrrole material prepared in Example 1 of this invention at different concentrations;

[0039] Figure 10 These are actual scanning electron microscope images of the sterilization process of UiO-66-Pyrrole and UiO-66-NH2 materials prepared in Example 1 of this invention;

[0040] Figure 11 This is a schematic diagram of the antibacterial UiO-66-Pyrrole prepared in Example 1 of the present invention. Detailed Implementation

[0041] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0042] Unless otherwise specified, all test materials and reagents used in the following examples are commercially available.

[0043] Unless otherwise specified in the embodiments, the techniques or conditions described in the literature in this field or in accordance with the product manual may be followed.

[0044] Example 1:

[0045] A method for the large-scale preparation of nano-UiO-66-NH2 includes the following steps: ZrCl4 (150 mg), 2-aminoterephthalic acid (100 mg), benzoic acid (3000 mg), and DMF (10 mL) are placed in a 20 mL reagent bottle, sonicated for 10 minutes, and then placed in a forced-air drying oven at 120 °C for 24 hours. After cooling to room temperature, the white product is collected by centrifugation and washed three times each with DMF and methanol. The wet sample is transferred to a vacuum drying oven and dried at 60 °C for 12 hours to obtain the parent MOF, i.e., nano-UiO-66-NH2.

[0046] A method for post-modification preparation of nano-derived UiO-66-Pyrrole includes the following steps: 0.6287 g of UiO-66-NH2, 278.42 μL of 2,5-dimethoxytetrahydrofuran (the molar ratio of UiO-66-NH2 to 2,5-dimethoxytetrahydrofuran is approximately 1:6), 10 mL of deionized water, and 1 mg of copper chloride are weighed into a 50 mL single-necked flask. The mixture is stirred slowly at 80 °C for 12 h under a nitrogen atmosphere. The brown solid product is centrifuged, washed three times each with deionized water and CHCl3, and then vacuum dried at 60 °C for 12 h to obtain the nano-scale MOF-derived material, UiO-66-Pyrrole.

[0047] Analysis of the UiO-66-NH2 and UiO-66-Pyrrole materials in this embodiment:

[0048] Powder diffraction analysis: The PXRD of UiO-66-Pyrrole is consistent with the diffraction peaks of the parent MOF (UiO-66-NH2), and no additional diffraction peaks were observed, indicating that the crystal structure was maintained after post-modification with Pyrrole (e.g., Figure 1 (As shown). The instrument used was an X-ray powder diffractometer (model D8 Advance, Bruker).

[0049] Infrared spectroscopy analysis (KBr, cm -1 ): By analyzing the Fourier transform infrared spectra of UiO-66-Pyrrole and UiO-66-NH2 powders, UiO-66-Pyrrole showed a high wavelength at 1585 cm⁻¹. -1 There is a peak at a certain point, which can be attributed to the characteristic peak of the C=C double bond in the pyrrole ring, indicating that the pyrrole ring was successfully modified into the framework in this experiment (e.g., Figure 2 (As shown). The instrument used was an FT-IR instrument (model VECTOR-22, Bruker).

[0050] Morphology analysis: Scanning electron microscopy (SEM) images show that the size and morphology of UiO-66-Pyrrole are consistent with the parent MOF (UiO-66-NH2), exhibiting an octahedral shape, with the main particle size being 50 nm (e.g., ...). Figure 3 As shown, A is UiO-66-NH2, and B is UiO-66-Pyrrole. The instrument used was a field emission scanning electron microscope (model SU8600, Hitachi).

[0051] N2 adsorption analysis: The specific surface area and pore size of UiO-66-Pyrrole and UiO-66-NH2 were measured by N2 adsorption / desorption at 77 K. Figure 4 As shown in the diagram (where A is the adsorption / desorption diagram and B is the pore size diagram), the surface area of ​​UiO-66-NH2 is 716.3735 m². 2 g -1 With a pore size of 2.87 nm, the specific surface area of ​​UiO-66-Pyrrole decreased to 581.4840 m² due to the introduction of Pyrrole. 2 g -1 The pore size was reduced to 2.56 nm. The instrument used was a fully automated surface area and porosity analyzer (model ASAP2460, Micromeritics).

[0052] Thermogravimetric analysis: Figure 5Thermogravimetric analysis (TGA) curves showed that both the parent MOF and the derived MOF experienced significant weight loss around 100 °C, with a weight loss rate of approximately 13%, attributed to the loss of guest molecules within the MOF structure. Subsequent TGA curves exhibited a plateau. At 520 °C, the framework structure of the parent MOF (UiO-66-NH2) began to collapse, while around 450 °C, the framework of the derived MOF (UiO-66-Pyrrole) also began to collapse, indicating a decrease in framework stability after Pyrrole modification. The instrument used was a comprehensive thermal analyzer (thermogravimetric analysis) (model STA409PC, NETZSCH).

[0053] UV-Vis absorption spectroscopy analysis: The characteristic absorption wavelength of UiO-66-NH2 is 362 nm. The characteristic absorption wavelength of the Pyrrole-modified MOF red-shifts to 378 nm, and the absorbance of UiO-66-Pyrrole is significantly greater than that of the parent MOF. This is because the introduction of pyrrole enhances the conjugation effect of the framework, increasing the material's absorption of UV-Vis light (e.g., ...). Figure 6 (As shown).

[0054] The post-modification reaction mechanism of the above-mentioned UiO-66-Pyrrole material is as follows: 2,5-dimethoxytetrahydrofuran is weakly coordinated with copper chloride. Under the attack of water molecules, ring opening occurs, generating a diol. Under the action of copper chloride, methanol is removed, generating a dialdehyde. Under the attack of UiO-66-NH2, dehydration occurs, generating intermediate (I). After hydrogen transfer isomerization, intermediate (II) is generated, and then dehydration is carried out to generate the target product UiO-66-Pyrrole (e.g., Figure 7 (As shown).

[0055] Antibacterial properties of UiO-66-Pyrrole, a MOF material derived from UiO-66:

[0056] The activated bacterial strains were added to the culture medium, and the OD value of the bacterial solutions was measured using a spectrophotometer. Bacterial solutions with an OD value of 0.6-0.8 were diluted with physiological saline to an OD value of 0.2, and then further diluted to a 10⁻⁶ level. -2 Weigh and prepare 10 mL of antibacterial material solutions of different concentrations (Pyrrole, UiO-66-NH2, and UiO-66-Pyrrole), with concentrations of 1 mg / L, 3 mg / L, and 5 mg / L, respectively. Transfer the antibacterial material solutions of different concentrations to 10 mL of LB liquid culture medium using a pipette and seal with sealing film. Place the required experimental materials in an autoclave for sterilization.

[0057] 50 μL of bacterial culture was added to sterile LB liquid medium cooled to room temperature without antibacterial material, serving as the blank group. 50 μL of bacterial culture was added to sterile LB liquid medium cooled to room temperature, along with pyrrole solution and UiO-66-NH2 solution, serving as the control group. 50 μL of bacterial culture was added to LB medium containing different concentrations of antibacterial material after cooling, serving as the experimental group. The blank group, control group, and experimental group were placed in a shaker at 37℃ and 150 rpm for 10 hours, and the mixed culture was removed. 100 μL of bacterial culture from each group was serially diluted to 10⁻¹⁰ in EP tubes. -6 times.

[0058] Use a pipette to transfer 50 μL of the diluted bacterial solution into an agar plate for spreading. Three plates each are used for the blank group, control group, and experimental group. After spreading, seal the plates with sealing film and incubate at 37°C. After 18 hours, remove the plates and test the sterilization effect of each group. Figure 8 As shown in the figure, at concentrations of 1 mg / L, 3 mg / L, and 5 mg / L, the survival rate of *E. coli* in the experimental group was significantly lower than that in the control group. For UiO-66-Pyrrole, its antibacterial effect increased in a gradient, and the results of the three experiments were almost identical. Figure 9 The survival status of E. coli before and after antibacterial treatment with UiO-66-Pyrrole and the control group UiO-66-NH2 is as follows: Figure 10 As shown, the derived nano-antibacterial material UiO-66-Pyrrole exhibits excellent antibacterial effects. Figure 11 This is a schematic diagram of the antibacterial UiO-66-Pyrrole prepared in Example 1 of the present invention.

[0059] Example 2:

[0060] A method for the large-scale preparation of nano-UiO-66-NH2 includes the following steps: ZrCl4 (100 mg), 2-aminoterephthalic acid (50 mg), benzoic acid (2750 mg), and DMF (10 mL) are placed in a 20 mL reagent bottle, sonicated for 10 minutes, and then placed in a forced-air drying oven at 140 °C for 20 hours. After cooling to room temperature, the white product is collected by centrifugation and washed three times each with DMF and methanol. The wet sample is transferred to a vacuum drying oven and dried at 60 °C for 12 hours to obtain the parent MOF, i.e., nano-UiO-66-NH2.

[0061] A method for post-modification preparation of nano-derived UiO-66-Pyrrole includes the following steps: 0.6287 g of UiO-66-NH2, 175 μL of 2,5-dimethoxytetrahydrofuran (the molar ratio of UiO-66-NH2 to 2,5-dimethoxytetrahydrofuran is approximately 1:4), 10 mL of deionized water, and 1 mg of copper chloride are weighed into a 50 mL single-necked flask. The mixture is stirred slowly at 80 °C for 12 h under a nitrogen atmosphere. The brown solid product is centrifuged, washed three times each with deionized water and CHCl3, and then vacuum dried at 60 °C for 12 h to obtain the nano-scale MOF-derived material, UiO-66-Pyrrole.

[0062] Example 3:

[0063] A method for the large-scale preparation of nano-UiO-66-NH2 includes the following steps: ZrCl4 (200 mg), 2-aminoterephthalic acid (150 mg), benzoic acid (3250 mg), and DMF (15 mL) are placed in a 20 mL reagent bottle, sonicated for 10 minutes, and then placed in a forced-air drying oven at 120 °C for 24 hours. After cooling to room temperature, the white product is collected by centrifugation and washed three times each with DMF and methanol. The wet sample is transferred to a vacuum drying oven and dried at 60 °C for 12 hours to obtain the parent MOF, i.e., nano-UiO-66-NH2.

[0064] A method for post-modification preparation of nano-derived UiO-66-Pyrrole includes the following steps: 0.6287 g of UiO-66-NH2, 340 μL of 2,5-dimethoxytetrahydrofuran (the molar ratio of UiO-66-NH2 to 2,5-dimethoxytetrahydrofuran is approximately 1:8), 10 mL of deionized water, and 1 mg of copper chloride are weighed into a 50 mL single-necked flask and stirred slowly at 80 °C for 12 h under a nitrogen atmosphere. The brown solid product is centrifuged, washed three times each with deionized water and CHCl3, and dried under vacuum at 60 °C for 12 h to obtain the nano-scale MOF-derived material, UiO-66-Pyrrole.

[0065] The morphology and properties of the UiO-66-Pyrrole materials prepared in Examples 2 and 3 are similar to those in Example 1.

[0066] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for post-modification preparation of derived nano-UiO-66-Pyrrole, characterized in that, Includes the following steps: A certain amount of UiO-66-NH2 and 2,5-dimethoxytetrahydrofuran were weighed, dissolved in deionized water, and CuCl2 was added as a catalyst. After heating and reaction, the derived nano-UiO-66-Pyrrole was obtained with a main particle size of 50 nm. The UiO-66-NH2 was prepared by the following method: ZrCl4, NH2-H2BDC and benzoic acid were placed in a reaction vessel and heated to react, and nano-UiO-66-NH2 was obtained.

2. The post-modification preparation method of the derived nano-UiO-66-Pyrrole according to claim 1, characterized in that, The mass ratio of ZrCl4, NH2-H2BDC and benzoic acid is (2-4):(1-3):(55-65).

3. The post-modification preparation method of the derived nano-UiO-66-Pyrrole according to claim 2, characterized in that, The mass ratio of ZrCl4, NH2-H2BDC and benzoic acid is 3:2:

60.

4. The post-modification preparation method of the derived nano-UiO-66-Pyrrole according to claim 1, characterized in that, When preparing UiO-66-NH2 ， The reaction conditions are 100-140 °C for 20-28 h.

5. The post-modification preparation method of the derived nano-UiO-66-Pyrrole according to claim 1, characterized in that, The molar ratio of UiO-66-NH2 to 2,5-dimethoxytetrahydrofuran is 1:4-8.

6. The post-modification preparation method of the derived nano-UiO-66-Pyrrole according to claim 5, characterized in that, The molar ratio of UiO-66-NH2 to 2,5-dimethoxytetrahydrofuran is 1:

6.

7. The post-modification preparation method of the derived nano-UiO-66-Pyrrole according to claim 1, characterized in that, UiO-66-NH2 and 2,5-dimethoxytetrahydrofuran were dissolved in deionized water and then dispersed by ultrasonication.

8. The method for post-modification preparation of derived nano-UiO-66-Pyrrole according to claim 1, characterized in that, The reaction conditions for preparing the derived nano-UiO-66-Pyrrole were reflux at 80 °C under nitrogen atmosphere and stirring for 12 h.

9. The derived nano-UiO-66-Pyrrole material prepared by the preparation method according to any one of claims 1-8.

10. The application of the derived nano-UiO-66-Pyrrole material according to claim 9 as an antibacterial material.

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