阅读说明：本技术 一种金属有机框架催化剂及制备方法、应用 (Metal organic framework catalyst, preparation method and application ) 是由 王征 王琳 刘志博 张红艳 汪洋 于 2021-10-09 设计创作，主要内容包括：本发明公开了一种金属有机框架催化剂及制备方法、应用,包括：1)配体四(4-羧基)三联苯甲烷的合成；2)有机配体和金属簇构筑金属有机框架催化剂的合成；3)催化磷脂化合物的效率计算和相关机制的探索。本发明采用无机有机杂化的策略,基于金属有机框架材料的优点,合成高孔的催化剂。有机杂化策略能降低金属的含量,提高催化的生物兼容性；高孔的结构能提升催化剂与客体分子的吸附接触能力,提高催化效率,从而达到性能的最优化。(The invention discloses a metal organic framework catalyst, a preparation method and application thereof, wherein the preparation method comprises the following steps: 1) synthesizing ligand tetra (4-carboxyl) terphenyl methane; 2) synthesizing an organic ligand and a metal cluster-constructed metal-organic framework catalyst; 3) efficiency calculations for catalyzing phospholipid compounds and the exploration of the relevant mechanisms. The invention adopts an inorganic-organic hybridization strategy and synthesizes the high-pore catalyst based on the advantages of metal organic framework materials. The organic hybridization strategy can reduce the content of metal and improve the biocompatibility of catalysis; the structure of the high pores can improve the adsorption contact capacity of the catalyst and guest molecules and improve the catalytic efficiency, thereby achieving the optimization of performance.)

1. A preparation method of a metal organic framework catalyst is characterized by comprising the following steps:

step 1, synthesizing ligand tetra (4-carboxyl) terphenyl methane;

step 2, synthesizing a metal organic framework catalyst: adding 2.2mg of the tetra (4-carboxyl) terphenylmethane, 2.6mg of ZrCl4,72mg of benzoic acid and 0.4mL of N, N-diethylformamide into a 4mL reaction bottle, and reacting at 120 ℃ for 3 days to obtain a metal organic framework catalyst with the particle size of about 100 microns;

step 3, synthesis of a nano-scale catalyst: reacting the tetra (4-carboxyl) terphenyl methane with 0.1M sodium hydroxide aqueous solution to generate a carboxylate ligand, evaporating the reaction aqueous solution to dryness, refluxing in ethanol for 1h, filtering, drying, dissolving solid powder in water, adding ZrCl4 aqueous solution and a little ground metal organic framework catalyst powder crystal, and standing at room temperature for 4 days to obtain the powdery solid catalyst with the particle size of about 170 nm.

2. The method for preparing the metal organic framework catalyst according to claim 1, wherein the ligand tetra (4-carboxy) terphenylmethane is synthesized by the following specific steps:

step 11, carrying out nucleophilic substitution reaction on triphenylmethanol and aniline to generate amino tetraphenylmethane;

step 12, carrying out diazotization reduction deamination on the amino tetraphenyl methane to generate tetraphenyl methane;

step 13, carrying out bromination reaction on tetraphenyl methane to generate tetrabromophenylmethane;

and step 14, carrying out Suzuki-Miyaura reaction on tetrabromophenylmethane and boric acid ester to generate ligand tetra (4-carboxyl) terphenylmethane.

3. The method of claim 1, further comprising an activation step of removing unreacted raw material and solvent molecules in the catalyst material by activation, wherein the activation step comprises the following steps: soaking the nano-scale catalyst prepared in the step 3 into anhydrous N, N-dimethylformamide, and exchanging at 80 ℃ for 3 days, wherein the liquid is exchanged 3 times per day; then immersing in acetone, exchanging for 3-5 days, and exchanging liquid for 3-5 times every day; the resulting catalyst is then exchanged with supercritical carbon dioxide.

4. The method for preparing a metal organic framework catalyst according to claim 3, wherein the obtained catalyst is exchanged with supercritical carbon dioxide, specifically: firstly, putting a catalyst in a sample chamber of a supercritical carbon dioxide drying instrument, adding liquid carbon dioxide in the sample chamber, keeping for 1h, then discharging carbon dioxide, adding new liquid carbon dioxide, and repeating the operation for 3 times; the sample chamber filled with carbon dioxide was then heated to 35 ℃ and maintained at this state for 1h before releasing the carbon dioxide to give a porous dry catalyst material.

5. A metal-organic framework catalyst obtained by the production method according to any one of claims 1 to 4.

6. Use of a metal organic framework catalyst according to claim 5 for the hydrolysis of phospholipid bonds.

Technical Field

The invention relates to the technical field of catalyst material synthesis, in particular to a metal organic framework catalyst, a preparation method and application thereof.

Background

Phospholipidic bonds are very common in organisms, such as DNA, RNA, phospholipidated proteins and ATP, among others. Catalyzing the hydrolysis of phospholipid bonds can modulate protein activity and DNA and RNA stability, further enabling the development of different therapeutic approaches. Therefore, designing and synthesizing the catalyst for catalyzing the phospholipid bond has important significance in the field of biomedicine.

Catalysts that have been reported to catalyze hydrolysis of phospholipid bonds are inorganic nanoparticles or small molecule compounds such as: cerium oxide nanoparticles (m.h. kuchma, c.b. komanski, j.colon, a.teblum, a.e. masunov, b.alvarado, s.babu, s.seal, j.summy, c.h. baker, nanomed.nanotechnol.,2010,6, 738-.

In addition, the patent of application No. 200710119249.4 discloses a method for degrading dye wastewater by using cerium oxide nanoparticles as a catalyst, which belongs to the technical field of application of cerium oxide nanoparticles. Is characterized in that firstly, cerium oxide nano particle powder is prepared by a hydrothermal method; and then adding cerium oxide nano particle powder into the reactive blue dye wastewater, and degrading the reactive blue dye wastewater by illumination. However, the biocompatibility and catalytic efficiency of these catalysts still need to be improved.

Disclosure of Invention

Technical problem to be solved

The invention aims to provide a metal organic framework catalyst, a preparation method and application thereof, and aims to solve the problems of unsatisfactory biocompatibility and low catalytic efficiency of the conventional catalyst for catalyzing hydrolysis of phospholipid bonds.

(II) technical scheme

In order to solve the problems of unsatisfactory biocompatibility and low catalytic efficiency of the existing catalyst for catalyzing hydrolysis of phospholipid bonds, the invention provides the following technical scheme:

a method of preparing a metal organic framework catalyst, comprising:

step 1, synthesizing ligand tetra (4-carboxyl) terphenyl methane;

step 2, synthesizing a metal organic framework catalyst: adding 2.2mg of the tetra (4-carboxyl) terphenylmethane, 2.6mg of ZrCl4,72mg of benzoic acid and 0.4mL of N, N-diethylformamide into a 4mL reaction bottle, and reacting at 120 ℃ for 3 days to obtain a metal organic framework catalyst with the particle size of about 100 microns;

step 3, synthesis of a nano-scale catalyst: reacting the tetra (4-carboxyl) terphenyl methane with 0.1M sodium hydroxide aqueous solution to generate a carboxylate ligand, evaporating the reaction aqueous solution to dryness, refluxing in ethanol for 1h, filtering, drying, dissolving solid powder in water, adding ZrCl4 aqueous solution and a little ground metal organic framework catalyst powder crystal, and standing at room temperature for 4 days to obtain the powdery solid catalyst with the particle size of about 170 nm.

Preferably, the synthesis of the ligand tetra (4-carboxyl) terphenylmethane comprises the following specific steps:

step 11, carrying out nucleophilic substitution reaction on triphenylmethanol and aniline to generate amino tetraphenylmethane;

step 12, carrying out diazotization reduction deamination on the amino tetraphenyl methane to generate tetraphenyl methane;

step 13, carrying out bromination reaction on tetraphenyl methane to generate tetrabromophenylmethane;

and step 14, carrying out Suzuki-Miyaura reaction on tetrabromophenylmethane and boric acid ester to generate ligand tetra (4-carboxyl) terphenylmethane.

Preferably, the preparation method of the metal organic framework catalyst further comprises an activation step of removing unreacted raw materials and solvent molecules in the catalyst material through activation, and the method of the activation step comprises the following steps: soaking the nano-scale catalyst prepared in the step 3 into anhydrous N, N-dimethylformamide, and exchanging at 80 ℃ for 3 days, wherein the liquid is exchanged 3 times per day; then immersing in acetone, exchanging for 3-5 days, and exchanging liquid for 3-5 times every day; the resulting catalyst is then exchanged with supercritical carbon dioxide.

Preferably, the obtained catalyst is exchanged with supercritical carbon dioxide, specifically: firstly, putting a catalyst in a sample chamber of a supercritical carbon dioxide drying instrument, adding liquid carbon dioxide in the sample chamber, keeping for 1h, then discharging carbon dioxide, adding new liquid carbon dioxide, and repeating the operation for 3 times; the sample chamber filled with carbon dioxide was then heated to 35 ℃ and maintained at this state for 1h before releasing the carbon dioxide to give a porous dry catalyst material.

The invention also provides a metal organic framework catalyst, which is obtained by the preparation method.

The invention also provides application of the metal organic framework catalyst in phospholipid bond hydrolysis.

(III) advantageous effects

Compared with the prior art, the invention provides a metal organic framework catalyst, a preparation method and application thereof, and the metal organic framework catalyst has the following beneficial effects: the invention adopts an inorganic-organic hybridization strategy and synthesizes the high-pore catalyst based on the advantages of metal organic framework materials. The organic hybridization strategy can reduce the content of metal and improve the biocompatibility of catalysis; the structure of the high pores can improve the adsorption contact capacity of the catalyst and guest molecules and improve the catalytic efficiency, thereby achieving the optimization of performance.

Drawings

FIG. 1 is a diagram showing the steps of synthesizing the organic ligand MTTC for synthesizing the metal-organic framework catalyst material according to the present invention.

FIG. 2 is a nuclear magnetic resonance hydrogen spectrum of the organic ligand tetrakis (4-carboxy) terphenylmethane of the catalyst material of the present invention.

FIG. 3 is a light mirror image of the metal organic framework catalyst obtained in example 6.

FIG. 4 is a graph showing the X-ray powder diffraction results of the metal-organic framework catalyst obtained in example 6.

FIG. 5 is a graph showing the results of nitrogen adsorption tests on the metal organic framework catalyst obtained in example 6.

FIG. 6 is a Fourier infrared spectrum of the metal organic framework catalyst obtained in example 6.

FIG. 7 is a graph showing the biocompatibility characterization of the nano-sized metal-organic framework catalyst obtained in example 7.

FIG. 8 is a graph of the efficiency of the nano-scale metal organic framework catalyst obtained in example 7 in catalyzing hydrolysis of phospholipid bonds.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

The invention relates to a metal organic framework catalyst, a preparation method and application thereof, comprising the following steps: 1) synthesizing ligand tetra (4-carboxyl) terphenyl methane; 2) synthesizing an organic ligand and a metal cluster-constructed metal-organic framework catalyst; 3) efficiency calculations for catalyzing phospholipid compounds and the exploration of the relevant mechanisms.

The synthesis of ligand tetra (4-carboxyl) terphenylmethane comprises the following specific steps: 1) nucleophilic substitution reaction of triphenylmethanol and aniline to produce amino tetraphenyl methane; 2) diazotization reduction deamination of the amino tetraphenyl methane to generate tetraphenyl methane; 3) bromination reaction of tetraphenyl methane generates tetrabromophenyl methane; 4) tetrabromophenylmethane and boric acid ester are subjected to Suzuki-Miyaura reaction to generate MTTC ligand (namely ligand tetra (4-carboxyl) terphenylmethane). See in particular the procedure of examples 1-5 below. FIG. 1 shows the steps of the synthesis of the organic ligand MTTC for the synthesis of metal organic framework catalyst materials according to the invention, i.e., the method described in examples 1-5. FIG. 2 is a nuclear magnetic resonance hydrogen spectrum of the organic ligand tetrakis (4-carboxy) terphenylmethane of the catalyst material of the present invention.

Example 1

Synthesis of amino tetraphenyl methane

14.3g of triphenylmethanol, 7.7mL of aniline, 200mL of acetic acid and 28mL of concentrated hydrochloric acid were added to a 500mL flask, heated at 120 ℃ for 8 hours, cooled to room temperature, and neutralized with 6M sodium hydroxide to obtain white powder of aminotetraphenylmethane. The pure product can be obtained by column chromatography with eluent of petroleum ether/dichloromethane (1: 1).

Example 2

Synthesis of tetraphenylmethane

850.9mg of tetraaminophenylmethane, 63.8mL of ethanol and 8.6mL of concentrated sulfuric acid are added into a 250mL flask, the mixture is cooled to-10 ℃ after mixing, 1.4mL of isoamyl nitrite is added, after stirring and reacting for 30min, 6.5mL of 50% hypophosphorous acid phosphoric acid is added, and then the temperature is raised to 80 ℃ for reacting for 20min, thus obtaining yellow tetraphenylmethane.

Example 3

Synthesis of tetrabromophenylmethane

Adding 5.0g of tetraphenylmethane into a 250mL flask, cooling to 0 ℃, dropwise adding 10mL of bromine water, slowly heating to room temperature for reaction for 20min, cooling to-78 ℃, adding 50mL of ethanol, heating to room temperature, adding a sodium sulfite solution to neutralize redundant bromine water, and thus obtaining a dark yellow product.

Example 4

Synthesis of 4-methoxycarbonyl terphenyl methane

A250 mL flask was charged with 1.0g of tetrabromophenylmethane, 1.8g of 4-methoxycarbonylbiphenylphenylboronic acid, 44.9mg of palladium dichloride triphenylphosphine, 50mL of saturated sodium bicarbonate, and 40mL of tetrahydrofuran. The reaction is carried out for 3 days at 70 ℃ under the protection of argon, the crude product is extracted with dichloromethane and the reaction is carried out with petroleum ether: the eluent column chromatography of dichloromethane to 1:3 can obtain the pure product, and the yield is 72.0%.

Example 5

Synthesis of tetra (4-carboxy) terphenylmethane

0.5g of 4-methoxycarbonyl terphenyl methane, 20mL of tetrahydrofuran, 20mL of ethanol and 20mL of 6M sodium hydroxide are added into a 250mL flask, the mixture is uniformly mixed and reacted at 70 ℃ for 8 hours, reactants are cooled and neutralized by 1M HCl to obtain a white crude product, the pure product is obtained by recrystallization with DMSO, and the yield is 87.0%.

Example 6

Synthesis of metal organic framework catalyst for micron-sized efficient catalysis of phospholipid bond hydrolysis

2.2mg of tetra (4-carboxy) terphenylmethane, 2.6mg of ZrCl4,72mg of benzoic acid and 0.4mL of N, N-diethylformamide are added into a 4mL reaction flask, and the mixture reacts for 3 days at 120 ℃ to obtain the organic framework catalyst with the particle size of about 100 microns.

FIG. 3 is a light mirror image of the metal organic framework catalyst obtained in the present example.

FIG. 4 is a graph showing the X-ray powder diffraction results of the metal-organic framework catalyst obtained in this example. The X-ray powder diffraction is obtained by placing the material on an X-ray powder diffractometer for testing, and the test result shows that the synthesized material has a crystalline structure. The X-ray diffraction curve is completely consistent with the simulated curve, and the X-ray diffraction curve and the simulated curve show stronger strength, which shows that the metal organic framework catalyst has higher purity and basically does not contain impurities, which shows that the preparation method of the invention has good repeatability and accuracy.

Fig. 5 is a graph showing the results of nitrogen adsorption tests of the metal organic framework catalyst obtained in this example. The nitrogen adsorption experiment is carried out at the temperature of 77K on a gas adsorption instrument, the test result can be used for analyzing the specific surface area of the catalyst, and the result shows that the synthetic catalyst material has higher specific surface area. The specific surface area of the material was found by fitting to be 3120 square meters per gram. The small graph in the figure is the pore size distribution of the material obtained by nitrogen adsorption fitting.

FIG. 6 is a Fourier infrared spectrum of the metal organic framework catalyst obtained in this example. Compared with a pure organic ligand, the main characteristic peaks of the catalyst material are obviously shifted, which indicates that the metal and the organic ligand in the catalyst are coordinately bonded.

Example 7

Synthesis of metal organic frame catalyst for nano efficient catalysis of phospholipid bond hydrolysis

Reacting tetra (4-carboxyl) terphenyl methane with 0.1M sodium hydroxide aqueous solution to generate a carboxylate ligand, evaporating the reaction aqueous solution to dryness, refluxing in ethanol for 1h, filtering, drying, dissolving solid powder in water, adding ZrCl4 aqueous solution and a little ground metal organic framework catalyst powder crystal, and standing at room temperature for 4 days to obtain the catalyst with the particle size of about 170 nm.

FIG. 7 is a graph showing the biocompatibility characterization of the nano-scale metal organic framework catalyst obtained in this example, including CCK-8 and flow type, and this experiment shows that HCT-116 cell activity can still reach 93.5% even if the concentration of the catalyst reaches 1200. mu.g mL-1, thus demonstrating that the catalyst has very good biocompatibility.

FIG. 8 is a graph showing the efficiency of the nano-scale metal organic framework catalyst obtained in this example in catalyzing hydrolysis of phospholipid bonds. Experiments show that the hydrolysis efficiency can reach 90% within 1 h.

In conclusion, the metal organic framework catalyst has the advantages that the metal organic framework catalyst is very good in biocompatibility, and even if the using concentration of the catalyst reaches 1200 mu g mL-1, the activity of HCT-116 cells can still reach 93.5%, and the catalytic efficiency can reach 90%, so that the catalyst has a very good biological application prospect.

It is noted that, herein, relational terms such as first and second, and the like may be used solely to distinguish one entity or action from another entity or action without necessarily requiring or implying any actual such relationship or order between such entities or actions. Also, the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus. Without further limitation, an element defined by the phrase "comprising an … …" does not exclude the presence of other identical elements in a process, method, article, or apparatus that comprises the element.

Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.