阅读说明：本技术 一种聚多巴胺包裹锆基金属有机材料、制备方法及其应用 (Polydopamine-coated zirconium-based metal organic material, preparation method and application thereof ) 是由 吴水林 韩冬琳 刘想梅 于 2019-09-02 设计创作，主要内容包括：本发明公开了一种聚多巴胺包裹锆基金属有机材料的制备方法,包括：步骤1,将卟啉衍生物,锆盐,苯甲酸类小分子均匀分散至有机溶剂中,使用水热法制备得到金属有机框架结构；步骤2,将步骤1得到的金属有机框架结构清洗,再分散在溶解有多巴胺的tris-HCl缓冲溶液中,反应6～24小时,反应温度15～30℃,得到聚多巴胺包裹锆基金属有机材料。聚多巴胺可以有效改善颗粒在水中的分散性,有效提高了材料的利用率。该材料还可以吸收可见光升温并产生大量活性氧(ROS)来实现光热、光动力协同杀菌,可以在较低的自由基需求量下实现对细菌的有效杀伤。(The invention discloses a preparation method of a polydopamine-coated zirconium-based metal organic material, which comprises the following steps: step 1, uniformly dispersing porphyrin derivatives, zirconium salt and benzoic acid micromolecules into an organic solvent, and preparing a metal organic framework structure by using a hydrothermal method; and 2, cleaning the metal organic framework structure obtained in the step 1, dispersing the metal organic framework structure in tris-HCl buffer solution in which dopamine is dissolved, and reacting for 6-24 hours at the reaction temperature of 15-30 ℃ to obtain the polydopamine-coated zirconium-based metal organic material. The polydopamine can effectively improve the dispersibility of the particles in water and effectively improve the utilization rate of the material. The material can also absorb visible light to raise the temperature and generate a large amount of Reactive Oxygen Species (ROS) to realize photo-thermal and photo-dynamic synergistic sterilization, and can realize effective killing of bacteria under low free radical demand.)

1. A preparation method of a polydopamine-coated zirconium-based metal organic material is characterized by comprising the following steps:

step 1, preparing a metal organic framework structure, uniformly dispersing porphyrin derivatives, zirconium salts and benzoic acid micromolecules into an organic solvent, wherein the mass ratio of the porphyrin derivatives to the zirconium salts to the benzoic acid micromolecules is 1: (2-5): (10-50), wherein the mass ratio of the organic solvent to the porphyrin derivative is (2-4): 1, preparing a metal organic framework structure by using a hydrothermal method;

the porphyrin derivative is meso-tetra (4-carboxyphenyl) porphin;

the zirconium salt is zirconium oxychloride or zirconium chloride;

the benzoic acid micromolecules are benzoic acid or phthalic acid;

the organic solvent is dimethylformamide;

and 2, cleaning the metal organic framework structure obtained in the step 1, and dispersing the metal organic framework structure in a tris (hydroxymethyl) aminomethane-hydrochloric acid buffer solution dissolved with dopamine, wherein the mass ratio of the buffer solution to the metal organic framework structure is (100-1000): 1, reacting for 6-24 hours at the reaction temperature of 15-30 ℃ to obtain a polydopamine-coated zirconium-based metal organic material; the pH value of the buffer solution is 7-9, and the dopamine concentration of the buffer solution is 0.5-5 mg/ml.

2. The preparation method of claim 1, wherein in the step 1, the porphyrin derivative, the zirconium salt and the benzoic acid small molecule are uniformly dispersed in the organic solvent by using an ultrasonic method, and the frequency of the ultrasonic is 25 KHZ-500 KHZ.

3. The method according to claim 1, wherein in step 1, the zirconium salt is zirconium oxychloride hydrate 8.

4. The preparation method according to claim 1, wherein in the step 1, the reaction temperature of the hydrothermal method is 90-130 ℃, and the reaction time is 12-24 h.

5. The method according to claim 1, wherein the hydrothermal reaction in step 1 is carried out in an autoclave.

6. The method according to claim 1, wherein in step 2, the metal-organic framework structure obtained in step 1 is washed with dimethylformamide.

7. The method according to claim 1, wherein the reaction process of step 2 is carried out under ultrasonic oscillation.

8. A preparation method of a polydopamine-coated zirconium-based metal organic material is characterized by comprising the following steps:

step 1, preparing a metal organic framework structure, uniformly dispersing meso-tetra (4-carboxyphenyl) porphin, 8-hydrated zirconium oxychloride and benzoic acid into dimethylformamide by adopting an ultrasonic method, wherein the mass ratio of the meso-tetra (4-carboxyphenyl) porphin to the 8-hydrated zirconium oxychloride to the benzoic acid is 1: 3: 30, the mass ratio of the organic solvent to the meso-tetra (4-carboxyphenyl) porphin is 3: 1, preparing a metal organic framework structure by using a hydrothermal method, wherein the reaction temperature of the hydrothermal method is 120 ℃, and the reaction time is 24 hours;

and 2, cleaning the metal organic framework structure obtained in the step 1 by using dimethylformamide for 3 times, and dispersing in a tris (hydroxymethyl) aminomethane-hydrochloric acid buffer solution dissolved with dopamine, wherein the mass ratio of the buffer solution to the metal organic framework structure is 200: 1, performing ultrasonic vibration and light-shielding reaction for 12 hours at room temperature to obtain a polydopamine-coated zirconium-based metal organic material; the pH value of the buffer solution is 8.5, and the dopamine concentration of the buffer solution is 2 mg/ml.

9. A polydopamine coated zirconium based metal organic material prepared according to the method of any one of claims 1 to 8.

10. Application of the polydopamine-coated zirconium-based metal organic material prepared by the method according to any one of claims 1 to 8 in the fields of antibiosis and sterilization, in particular in a sterilization material.

Technical Field

The invention belongs to the technical field of biological materials, and particularly relates to a polydopamine-coated zirconium-based metal organic material, a preparation method and application thereof.

Background

It is a very common occurrence in daily life that wounds appear on the skin. In the process of wound healing, if bacterial infection occurs, the speed of wound healing is affected, and even the wound can not heal. The use of antibiotics is currently the most common treatment option in order to avoid bacterial infections of wounds. And the use of a large amount of antibiotics promotes the generation of drug-resistant bacteria. These drug-resistant bacteria can be invisibly attacked by most antibiotics, so that the current situation that no drugs are available is caused, and the life of human beings is threatened. Therefore, the development of new, fast, effective, non-antibiotic antimicrobials is at hand.

Photosensitizers can generate heat and free radicals under the condition of light, and at present, a plurality of photosensitizers are applied to the treatment of skin diseases and even cancers. Porphyrins and their derivatives are currently the most common photosensitizers. However, the existing photosensitizers are small molecules, particularly porphyrin and derivatives thereof, have strong hydrophobic property, and can obviously agglomerate under the aqueous condition to cause a fluorescence quenching phenomenon and reduce the utilization rate of the photosensitizers.

The existing photosensitizer cannot generate enough heat under the illumination condition, the effective and quick killing of bacteria cannot be realized by only depending on generated free radicals, and the antibacterial capacity needs to be further improved.

Disclosure of Invention

The invention aims to overcome the defects of the prior art and provide a polydopamine-coated zirconium-based metal organic material, wherein polydopamine can effectively improve the dispersibility of particles in water, endows the material with better dispersibility and effectively improves the utilization rate of the material. Meanwhile, after the dopamine is wrapped, the material can absorb visible light to heat, the photo-thermal capability of the material is greatly improved, a large amount of singlet oxygen is generated, and photo-thermal and photodynamic synergistic rapid sterilization is finally realized. Can effectively kill bacteria.

The invention also aims to provide a preparation method of the polydopamine-coated zirconium-based metal organic material.

The invention also aims to provide application of the polydopamine-coated zirconium-based metal organic material to skin surface wounds. As a photosensitive antibacterial agent, the bactericidal composition realizes quick and efficient sterilization under illumination.

The invention is realized by the following technical scheme:

a preparation method of a polydopamine-coated zirconium-based metal organic material comprises the following steps:

step 1, preparing a metal organic framework structure, uniformly dispersing porphyrin derivatives, zirconium salts and benzoic acid micromolecules into an organic solvent, wherein the mass ratio of the porphyrin derivatives to the zirconium salts to the benzoic acid micromolecules is 1: (2-5): (10-50), wherein the mass ratio of the organic solvent to the porphyrin derivative is (2-4): 1, preparing a metal organic framework structure by using a hydrothermal method;

the porphyrin derivative is meso-tetra (4-carboxyphenyl) porphin;

the zirconium salt is zirconium oxychloride or zirconium chloride;

the benzoic acid micromolecules are benzoic acid or phthalic acid;

the organic solvent is dimethylformamide;

step 2, cleaning the metal organic framework structure obtained in the step 1, and dispersing the metal organic framework structure in a tris-HCl (tris (hydroxymethyl) aminomethane-hydrochloric acid) buffer solution in which dopamine is dissolved, wherein the mass ratio of the buffer solution to the metal organic framework structure is 100-1000: 1, reacting for 6-24 hours at the reaction temperature of 15-30 ℃ to obtain a polydopamine-coated zirconium-based metal organic material; the pH value of the buffer solution is 7-9, and the dopamine concentration of the buffer solution is 0.5-5 mg/ml.

In the technical scheme, in the step 1, porphyrin derivatives, zirconium salts and benzoic acid micromolecules are uniformly dispersed into an organic solvent by adopting an ultrasonic method, wherein the ultrasonic frequency is 25 KHZ-500 KHZ.

In the above technical solution, in the step 1, the zirconium salt is 8 hydrous zirconium oxychloride.

In the technical scheme, in the step 1, the reaction temperature of the hydrothermal method is 90-130 ℃, and the reaction time is 12-24 hours.

In the above technical solution, in the step 1, the hydrothermal reaction is performed in an autoclave.

In the above technical solution, in the step 2, the metal organic framework structure obtained in the step 1 is cleaned by using dimethylformamide.

A preparation method of a polydopamine-coated zirconium-based metal organic material comprises the following steps:

step 1, preparing a metal organic framework structure, uniformly dispersing meso-tetra (4-carboxyphenyl) porphin, 8-hydrated zirconium oxychloride and benzoic acid into dimethylformamide, wherein the mass ratio of the meso-tetra (4-carboxyphenyl) porphin to the 8-hydrated zirconium oxychloride to the benzoic acid is 1: 3: 30, the mass ratio of the organic solvent to the meso-tetra (4-carboxyphenyl) porphin is 3: 1, preparing a metal organic framework structure by using a hydrothermal method, wherein the reaction temperature of the hydrothermal method is 120 ℃, and the reaction time is 24 hours;

and 2, cleaning the metal organic framework structure obtained in the step 1 by using dimethylformamide for 3 times, and dispersing in a tris-HCl (tris (hydroxymethyl) aminomethane-hydrochloric acid) buffer solution dissolved with dopamine, wherein the mass ratio of the buffer solution to the metal organic framework structure is 20: 1, performing ultrasonic vibration and light-shielding reaction for 12 hours at room temperature to obtain a polydopamine-coated zirconium-based metal organic material; the pH value of the buffer solution is 8.5, and the dopamine concentration of the buffer solution is 2 mg/ml.

The application of the polydopamine-coated zirconium-based metal organic material prepared by the technical scheme in the antibacterial and bactericidal fields.

The application of the polydopamine-coated zirconium-based metal organic material prepared by the technical scheme in a sterilization material.

The invention has the advantages and beneficial effects that:

the poly-dopamine is modified on the surface of the metal organic framework structure, so that the dispersibility of the metal organic framework structure in water can be effectively improved, and the utilization rate of the material is improved. Meanwhile, due to the high photo-thermal conversion efficiency of the polydopamine, the photo-thermal conversion capability of the metal-organic framework structure can be remarkably improved after the polydopamine is modified. Meanwhile, the modification of polydopamine greatly improves the photodynamic effect of the metal organic framework. The main reason is that the poly dopamine and porphyrin derivative have pi-pi interaction and mutual electron transfer, so that the energy band gap of the metal organic framework structure is reduced, and the ability of the metal organic framework structure to generate free radicals under the illumination condition is improved. After the polydopamine is modified, the light absorption of the material is obviously improved, so that the material generates more heat and free radicals under illumination. Under the condition of illumination, the free radicals and heat generated by the material can synergistically kill bacteria. Finally, effective killing of bacteria is achieved at a relatively low free radical concentration.

The polydopamine-coated metal organic framework structure material prepared by the invention can generate a large amount of heat and free radicals under the irradiation of visible light, and can efficiently and quickly sterilize and realize the disinfection of the vicinity of a wound through the synergistic effect of the heat and the free radicals.

The prepared polydopamine modified metal organic framework structure has high stability and biocompatibility, and has potential prospect as a wound disinfectant. Meanwhile, the preparation method is simple and easy to implement, free of toxic and harmful gases, economical, environment-friendly, low in implementation difficulty, low in equipment investment and low in resource consumption.

Drawings

FIG. 1 is the XRD characterization of example 3;

wherein A is: b, coating the polydopamine obtained in step 2 on a zirconium-based metal organic material to obtain a metal organic framework structure obtained in step 1;

FIG. 2 is a TEM and element distribution diagram of the polydopamine-coated zirconium-based metal-organic material obtained in example 3;

FIG. 2(A) is a TEM image of polydopamine coated zirconium-based metal-organic material;

FIG. 2(B) is an element distribution diagram of C of polydopamine coated zirconium-based metal-organic material;

FIG. 2(C) is an element distribution diagram of N of polydopamine coated zirconium-based metal-organic material;

FIG. 2(D) is an elemental distribution diagram of O in polydopamine coated zirconium-based metal-organic material;

FIG. 2(E) is an elemental distribution diagram of Zr in a polydopamine coated zirconium-based metal-organic material;

FIG. 3 shows the dispersibility of the metal-organic framework structure obtained in step 1 and the polydopamine-coated zirconium-based metal-organic material obtained in step 2 of example 3;

a is a metal organic framework structure, and B is a polydopamine-coated zirconium-based metal organic material;

FIG. 4 shows the photothermal properties of the metal-organic framework structure obtained in step 1 and the polydopamine-coated zirconium-based metal-organic material obtained in step 2 of example 3;

FIG. 5 is a representation of the singlet oxygen generating capacity of example 3,

wherein A is: b, coating the polydopamine obtained in step 2 on a zirconium-based metal organic material to obtain a metal organic framework structure obtained in step 1; the curves in the figure represent curves from top to bottom for 0, 10, 20, 30, 40, 50 and 60 seconds of light exposure time, respectively.

FIG. 6 shows the antibacterial effect of the metal-organic framework structure obtained in step 1 of example 3;

FIG. 6(A) is the result of plate coating with killing property to Staphylococcus aureus under dark condition of metal-organic framework structure;

FIG. 6(B) is the result of plate coating with killing property to Staphylococcus aureus under the condition of light irradiation of metal-organic framework structure;

FIG. 6(C) is the result of plate coating of the metal-organic framework structure with killing property to Escherichia coli in dark;

FIG. 6(D) is the result of plate coating of the metal-organic framework structure under light conditions for killing of E.coli;

FIG. 7 shows the antibacterial effect of the polydopamine-coated zirconium-based metal-organic material obtained in example 3;

FIG. 7(A) is the result of plate coating of poly-dopamine coated zirconium-based metal-organic material with killing property against Staphylococcus aureus in dark;

FIG. 7(B) is the result of plate coating of polydopamine coated zirconium-based metal-organic material with killing property against Staphylococcus aureus under illumination;

FIG. 7(C) is the result of plate coating of poly-dopamine coated zirconium-based metal-organic material with killing property to Escherichia coli in dark condition;

FIG. 7(D) is the result of plate coating of polydopamine coated zirconium-based metal-organic material with killing property to Escherichia coli under illumination condition;

for a person skilled in the art, other relevant figures can be obtained from the above figures without inventive effort.

Detailed Description

In order to make the technical solution of the present invention better understood, the technical solution of the present invention is further described below with reference to specific examples.

Example one

A preparation method of a polydopamine-coated zirconium-based metal organic material comprises the following steps:

step 1, preparing a metal organic framework structure, adding 40mg of meso-tetra (4-carboxyphenyl) porphine, 120mg of zirconium oxychloride monohydrate and 1200mg of benzoic acid into 8mL of dimethylformamide, performing ultrasonic treatment (300kHZ, 20min) to completely dissolve the zirconium oxychloride, adding the solution into a high-pressure reaction kettle, and preparing the metal organic framework structure by using a hydrothermal method, wherein the reaction temperature of the hydrothermal method is 120 ℃, the reaction time is 24h, and then gradually and slowly recovering the room temperature;

step 2, cleaning the metal organic framework structure obtained in the step 1 by using dimethylformamide for 3 times, and dispersing the metal organic framework structure in tris-HCl (tris (hydroxymethyl) aminomethane-hydrochloric acid) buffer solution dissolved with dopamine, wherein the mass ratio of the buffer solution to the metal organic framework structure is 200: 1, performing ultrasonic vibration and light-shielding reaction for 12 hours at room temperature to obtain a polydopamine-coated zirconium-based metal organic material; the pH value of the buffer solution is 8.5, and the dopamine concentration of the buffer solution is 0.5 mg/ml.

Example two

A preparation method of a polydopamine-coated zirconium-based metal organic material comprises the following steps:

step 1, preparing a metal organic framework structure, adding 40mg of meso-tetra (4-carboxyphenyl) porphine, 120mg of zirconium oxychloride monohydrate and 1200mg of benzoic acid into 8mL of dimethylformamide, performing ultrasonic treatment (300kHZ, 20min) to completely dissolve the zirconium oxychloride, adding the solution into a high-pressure reaction kettle, and preparing the metal organic framework structure by using a hydrothermal method, wherein the reaction temperature of the hydrothermal method is 120 ℃, the reaction time is 24h, and then gradually and slowly recovering the room temperature;

step 2, cleaning the metal organic framework structure obtained in the step 1 by using dimethylformamide for 3 times, and dispersing the metal organic framework structure in tris-HCl (tris (hydroxymethyl) aminomethane-hydrochloric acid) buffer solution dissolved with dopamine, wherein the mass ratio of the buffer solution to the metal organic framework structure is 200: 1, performing ultrasonic vibration and light-shielding reaction at room temperature overnight to obtain a polydopamine-coated zirconium-based metal organic material; the pH value of the buffer solution is 8.5, and the dopamine concentration of the buffer solution is 1 mg/ml.

EXAMPLE III

A preparation method of a polydopamine-coated zirconium-based metal organic material comprises the following steps:

step 1, preparing a metal organic framework structure, adding 40mg of meso-tetra (4-carboxyphenyl) porphine, 120mg of zirconium oxychloride monohydrate and 1200mg of benzoic acid into 8mL of dimethylformamide, performing ultrasonic treatment (300kHZ, 20min) to completely dissolve the zirconium oxychloride, adding the solution into a high-pressure reaction kettle, and preparing the metal organic framework structure by using a hydrothermal method, wherein the reaction temperature of the hydrothermal method is 120 ℃, the reaction time is 24h, and then gradually and slowly recovering the room temperature;

step 2, cleaning the metal organic framework structure obtained in the step 1 by using dimethylformamide for 3 times, and dispersing the metal organic framework structure in tris-HCl (tris (hydroxymethyl) aminomethane-hydrochloric acid) buffer solution dissolved with dopamine, wherein the mass ratio of the buffer solution to the metal organic framework structure is 200: 1, performing ultrasonic vibration and light-shielding reaction at room temperature overnight to obtain a polydopamine-coated zirconium-based metal organic material; the pH value of the buffer solution is 8.5, and the dopamine concentration of the buffer solution is 2 mg/ml.

Example four

A preparation method of a polydopamine-coated zirconium-based metal organic material comprises the following steps:

step 1, preparing a metal organic framework structure, adding 40mg of meso-tetra (4-carboxyphenyl) porphine, 120mg of zirconium oxychloride monohydrate and 1200mg of benzoic acid into 8mL of dimethylformamide, performing ultrasonic treatment (300kHZ, 20min) to completely dissolve the zirconium oxychloride, adding the solution into a high-pressure reaction kettle, and preparing the metal organic framework structure by using a hydrothermal method, wherein the reaction temperature of the hydrothermal method is 120 ℃, the reaction time is 24h, and then gradually and slowly recovering the room temperature;

step 2, cleaning the metal organic framework structure obtained in the step 1 by using dimethylformamide for 3 times, and dispersing the metal organic framework structure in tris-HCl (tris (hydroxymethyl) aminomethane-hydrochloric acid) buffer solution dissolved with dopamine, wherein the mass ratio of the buffer solution to the metal organic framework structure is 200: 1, performing ultrasonic vibration and light-shielding reaction at room temperature overnight to obtain a polydopamine-coated zirconium-based metal organic material; the pH value of the buffer solution is 8.5, and the dopamine concentration of the buffer solution is 3 mg/ml.

The experimental results show that the final products obtained in step 2 of examples 1, 2, 3 and 4 differ from each other in the roughness of the particle surface and the thickness of the polydopamine shell layer obtained, but are not significantly different from each other, and are characterized below by using the metal-organic framework structure prepared in step 1 of example 3 and the final product obtained in step 2.

As shown in fig. 1, the crystal structure of the obtained metal-organic framework structure is not changed significantly after the modification of polydopamine, and the XRD peak position is the same as that before the modification of polydopamine. The method shows that the metal organic framework structure does not collapse in structure and deform in crystal form in the polydopamine modification process.

And as can be confirmed by TEM characterization in fig. 2, a layer of rough shell is formed on the periphery of the metal-organic framework after the poly-dopamine modification. The element surface distribution result shows that the element distribution diagram of the rough shell at the periphery of the metal organic framework is obviously larger than that of N and Zr, wherein the main component of the rough shell is C, and the element distribution diagram of C is obviously larger than that of N and Zr, so that a layer of dopamine is successfully wrapped around the metal organic framework.

The experiment in fig. 3 confirms that the simple metal organic framework structure has poor dispersibility in water, and the material is obviously settled at the bottom when dispersed in water for 2.5 hours. But the metal organic framework structure wrapped by dopamine has better stability in water, and the solution does not have obvious layering phenomenon after being dispersed for 2.5 hours. The dopamine encapsulation is shown to successfully improve the dispersibility of the material.

The photothermal curve of fig. 4 demonstrates that the photothermal conversion efficiency is significantly improved after dopamine encapsulation. Under the same illumination condition, the metal organic framework structure wrapped with dopamine has better photo-thermal performance. The metal organic framework structure can effectively kill bacteria by combining the capability of generating free radicals under illumination.

FIG. 5, using 1, 3-diphenylisobenzofuran as a probe, the production of singlet oxygen can be detected. Mixing the 1, 3-diphenyl isobenzofuran solution materials, illuminating, and measuring the light absorption of the solution at 415 nm at different illumination time points for characterizing the singlet oxygen generating capacity of the material. 1, 3-diphenyl isobenzofuran reacts with singlet oxygen, and the absorption of the generated substance at the wavelength of 415 nm is obviously reduced. As shown in a of fig. 5, before coating dopamine, the absorption of the mixture of the metal-organic framework and 1, 3-diphenylisobenzofuran at 41 nm was greatly reduced under the illumination condition, indicating that the metal-organic framework can generate singlet oxygen under the illumination condition. But the intensity of light absorption reduction under illumination is obviously improved after the polydopamine is wrapped, which shows that the capacity of the material for generating singlet oxygen is greatly improved.

The plate antibacterial result shows that the bacteria quantity is not reduced and the colony quantity on the agarose solid culture medium is still large after the zirconium-based metal material powder is mixed with the bacteria liquid (10^7, staphylococcus aureus and escherichia coli) for 20min under the dark condition. Indicating that the sterilization capacity of the material is low under dark conditions. After the light, the number of bacteria was reduced, but not obvious, as shown in fig. 6B, D. The zirconium-based metal organic framework structure does not have bactericidal performance under dark conditions. But under the condition of light, the bacteria can be killed, but the effect is weak.

Under dark conditions, the powder was mixed with bacterial solution (10^7, Staphylococcus aureus and Escherichia coli) for 20min, and the bacteria were not effectively killed. The number of colonies on agarose solid medium is still large. After light irradiation, as shown in fig. 7B and D, the bacteria were killed rapidly and effectively, and almost no colony grew on the medium. The poly-dopamine coated metal organic framework structure is shown to have no bactericidal performance under dark conditions. But can effectively kill bacteria under the condition of illumination.

The invention has been described in an illustrative manner, and it is to be understood that any simple variations, modifications or other equivalent changes which can be made by one skilled in the art without departing from the spirit of the invention fall within the scope of the invention.