Preparation method of capillary electrochromatography monolithic column of nano material synthesized based on chiral metal organic framework and chiral molecularly imprinted polymer

Abstract

The invention relates to the technical field of chemical synthesis and analysis, in particular to a preparation method of a capillary electrochromatography monolithic column of a nano material synthesized based on a chiral metal organic framework and a chiral molecularly imprinted polymer. The preparation method comprises the following steps: synthesizing L-His-ZIF-8 by using zinc nitrate hexahydrate, L-His and 2-MM, then carrying out vinyl modification on the L-His-ZIF-8 by using GMA to obtain Vinyl-L-His-ZIF-8, then preparing a Vinyl-L-His-ZIF-8 dispersion liquid by using the Vinyl-L-His-ZIF-8, rac-DCPP, PG, EDMA and AIBN, filling a vinyl modified capillary with the Vinyl-L-His-ZIF-8 dispersion liquid, and carrying out reaction, elution and blow-drying to obtain the capillary electrochromatography monolithic column. According to the preparation method, the synergistic effect between the L-His-ZIF-8 and the CMIPs which have chiral selection ability is utilized, so that the effect that 1 + 1 is greater than 2 is achieved, and the chiral resolution ability of the capillary monolithic column is greatly improved.

Description

Technical Field

[0001] The present invention relates to the technical field of chemical synthesis and analysis, and particularly to a preparation method of a capillary electrochromatography monolithic column made of a nanomaterial synthesized based on a chiral metal-organic framework and a chiral molecularly imprinted polymer. Background Art

[0002] Capillary electrochromatography (CEC) is one of the most commonly used means in the field of chiral separation. It combines the characteristics of high-performance capillary electrophoresis (HPCE) and high-performance liquid chromatography (HPLC), has a dual separation mechanism, and has the advantages of low consumption, high selectivity, and high analysis efficiency. According to the preparation method, capillary columns can be divided into coated columns, monolithic columns, and packed columns. Among them, monolithic columns have the advantages of good permeability, high repeatability, and strong resolution ability. Since there is a rich variety of functional monomers to choose from, the surface structure of the monolithic column stationary phase can be modified with a variety of chemical functional groups. Therefore, capillary monolithic columns have been widely studied and applied.

[0003] Molecularly imprinted polymers (MIPs) are one of the separation media that have become increasingly mature in recent decades. First, the template and the functional monomer interact to form a complex, and then the spatial position of the complex is fixed through the polymerization reaction of the cross-linking agent. Finally, after removing the template by elution, MIPs are obtained. MIPs are a kind of porous structure and have specific recognition for the template molecule. Chiral molecularly imprinted polymers (CMIPs) are a kind of MIPs with chiral recognition ability, have a wide range of porous structures, and have the advantages of low cost, good stability, and good chiral recognition ability, and have gradually become one of the important candidates for the stationary phase of capillary monolithic columns.

[0004] Since the recognition cavities of CMIP may collapse and deform during application, which will lead to a reduction in its chiral recognition ability, this is also one of the main difficulties faced in the related research of CMIPs. Therefore, the chiral separation effect of using CMIPs alone as the stationary phase of CEC is often not satisfactory. In addition, in previous studies, the preparation of CMIPs often requires a single enantiomer as the template, and the high price of the single enantiomer limits the wider application of CMIPs.

[0005] Metal-organic frameworks (MOFs) are formed by the self-assembly of metal ions / clusters and organic ligands, and have the characteristics of high stability, large specific surface area, adjustable, and easy to modify. Chiral metal-organic frameworks (CMOFs) are a class of MOFs with chiral characteristics. They not only have the inherent advantages of MOFs, but also have chiral channels and chiral selectivity, and are widely used in asymmetric catalysis, membrane separation, chiral stationary phases, and enantioselective sensors, etc.

[0006] CMOFs have a large specific surface area and a stable framework structure. When acting synergistically with CMIPs, they can provide a large number of binding sites and reduce the deformation and collapse of the pores of CMIPs. Therefore, the nanomaterials synthesized from CMIPs and CMOFs have excellent chiral selection performance, and using them as the stationary phase of the monolithic column can greatly improve the chiral separation performance of CEC.

[0007] Based on the above statements, this work developed a kind of CMIPs based on a racemate template (racemic 2,4-dichloropropionic acid, rac-DCPP), and synthesized a new nanomaterial with a chiral metal-organic framework (L-His-ZIF-8) as the stationary phase to prepare a novel capillary monolithic column (L-His-ZIF-8@CMIP(rac-DCPP / PG-EDMA)@capillary). This kind of nanomaterial synthesized from CMIP and CMOF as the stationary phase of the CEC system has not been reported internationally. Summary of the Invention

[0008] The object of the present invention is to provide a preparation method of a capillary electrochromatography monolithic column based on a nanomaterial synthesized from a chiral metal-organic framework and a chiral molecularly imprinted polymer. The prepared novel capillary monolithic column can be used to construct a CEC chiral separation system and complete the chiral separation of 2,4-dichloropropionic acid, which can solve the problem that the separation performance is not very satisfactory when using CMIPs alone as the separation medium. A method for preparing CMIPs with a racemate template is also developed, which greatly reduces the preparation cost of CMIPs and overcomes the limitation in previous studies that only a single enantiomer can be used as the template.

[0009] In order to achieve the above object, the specific technical solutions adopted by the present invention include the following steps:

[0010] (1) Pretreatment of the capillary: First, rinse the empty capillary with a sodium hydroxide solution for 1 h, and then rinse it with water until neutral. Then, rinse the capillary with a hydrochloric acid solution for 30 min and rinse it with water until neutral. Then, rinse it with methanol for 30 min, and then dry it with nitrogen and place it in an oven at 100 °C for 1 h. Finally, fill it with a methanol solution of 3-(methacryloyloxy)propyltrimethoxysilane (γ-MAPs) with a volume fraction of 45% - 55%, seal both ends, and place it in a water bath at 45 - 60 °C for reaction for 6 - 24 h. After the reaction, rinse it with methanol for 20 min and dry it with nitrogen, and store it at -4 °C to obtain a vinyl-modified capillary.

[0011] Preferably, the specification of the empty capillary in step (1) is an unmodified fused silica capillary with an inner diameter of 75 μm.

[0012] Preferably, the concentrations of the sodium hydroxide solution and the hydrochloric acid solution in step (1) are both 1 mol·L-1 .

[0013] Preferably, the volume fraction of the γ-MAPs methanol solution in step (1) is 50%.

[0014] Preferably, the reaction condition in step (1) is to react in a 55 °C water bath for 12 h.

[0015] (2) Preparation of chiral metal-organic framework (L-His-ZIF-8): 0.6 mmol of chiral ligand is dissolved in 8 mL of water, and 50 μL of triethylamine is added and stirred for 5 min to obtain a chiral ligand solution; 1.2 mmol of metal salt and 4.2 mmol of achiral organic ligand are respectively dissolved in 20 mL and 12 mL of methanol to obtain a metal salt solution and an achiral organic ligand solution; the chiral ligand solution is mixed with the achiral ligand solution, stirred for 15 min, and then the metal salt solution is added, and stirring is continued at room temperature for 24 h. After the reaction is completed, it is washed several times with methanol and dried at 60 °C to obtain L-His-ZIF-8.

[0016] Preferably, the metal salt in step (2) is zinc nitrate hexahydrate.

[0017] Preferably, the chiral organic ligand in step (2) is L-histidine (L-His).

[0018] Preferably, the achiral organic ligand in step (2) is 2-methylimidazole (2-MM).

[0019] Preferably, the molar ratio of the metal salt, chiral organic ligand and achiral organic ligand in step (2) is 2:1:7.

[0020] (3) Preparation of vinyl-modified L-His-ZIF-8 (Vinyl-L-His-ZIF-8): L-His-ZIF-8 is dispersed in a glycidyl methacrylate (GMA) solution, and stirring is continued at 55 °C for 6 h. After the reaction is completed, it is washed several times with methanol and dried at 60 °C to obtain Vinyl-L-His-ZIF-8.

[0021] Preferably, the GMA solution in step (3) is obtained by mixing GMA and methanol in a volume ratio of 1:9.

[0022] Preferably, the dosage ratio of L-His-ZIF-8 and GMA solution in step (3) is 1 mg:1 mL.

[0023] (4) Preparation of monolithic capillary electrochromatography column: First, dissolve the template and functional monomer in a mixed solvent, stir at room temperature for 30 min, then add the crosslinking agent and stir for 20 min to obtain a mixed solution; Disperse Vinyl-L-His-ZIF-8 in 1 mL of the mixed solution, stir for 5 min, add azobisisobutyronitrile (AIBN), perform ultrasonic treatment for 30 min, and then blow with nitrogen for 5 min to obtain a Vinyl-L-His-ZIF-8 dispersion; Finally, fill the vinyl-modified capillary with the Vinyl-L-His-ZIF-8 dispersion, seal both ends, react at 50-85 °C for 2-6 h. After the reaction, rinse the capillary column with the eluent for 2-6 h to elute the template and unreacted reagents, and finally dry it with nitrogen to obtain the monolithic capillary electrochromatography column L-His-ZIF-8@CMIP(rac-DCPP / PG-EDMA)@capillary.

[0024] Preferably, in step (4), the template is racemic 2,4-dichlorophenoxypropionic acid (rac-DCPP), and the addition amount is 0.1-0.4 mmol.

[0025] Preferably, in step (4), the functional monomer is allyl-β-D-pyranosyl galactoside (PG), and the addition amount is 0.5-1.5 mmol.

[0026] Preferably, in step (4), the crosslinking agent is ethylene glycol dimethacrylate (EDMA), and the addition amount is 2-8 mmol.

[0027] Preferably, in step (4), the mixed solvent is a mixture of ethanol and methanol, V 乙醇： V 甲醇 = 3:2, and the addition amount is 1-5 mL.

[0028] More preferably, the addition amount of the mixed solvent in step (4) is 2 mL.

[0029] More preferably, in step (4), the addition amounts of the template, functional monomer, and crosslinking agent are 0.25 mmol, 1 mmol, and 4 mmol.

[0030] Preferably, in step (4), the addition amount of Vinyl-L-His-ZIF-8 is 1-5 mg.

[0031] More preferably, in step (4), the addition amount of Vinyl-L-His-ZIF-8 is 2 mg.

[0032] Preferably, in step (4), the addition amount of AIBN is 1-3 mg.

[0033] More preferably, in step (4), the addition amount of AIBN is 2 mg.

[0034] Preferably, the reaction conditions in step (4) are to react at 70 °C for 4 h.

[0035] Preferably, the eluent in step (4) is a mixed solution of acetic acid and methanol, V 乙酸： V 甲醇 = 1:9.

[0036] Preferably, the time for the eluent to rinse the capillary column in step (4) is 4 h.

[0037] Advantages of the present invention:

[0038] The preparation method of the capillary monolithic column proposed by the present invention has the characteristics of simple preparation process, low cost, and good performance. CMIPs can be prepared using a racemate template, avoiding the use of expensive single enantiomers, greatly reducing the cost, and promoting the wider application of CMIPs. In addition, L-His-ZIF-8 has a stable pore structure and a rigid skeleton, which can effectively reduce the collapse and deformation of the pores of CMIP. During the preparation process of the monolithic column, both Vinyl-L-His-ZIF-8 and the vinyl groups on the inner wall of the capillary can participate in the free radical polymerization reaction, and Vinyl-L-His-ZIF-8 with a large specific surface area provides a large number of bonding sites, so that CMIPs, L-His-ZIF-8 and the inner wall of the capillary are tightly bonded together, greatly improving the stability of the capillary column. The synergistic effect between L-His-ZIF-8 with chiral selectivity and CMIPs achieves an effect of 1 + 1 > 2, greatly improving the chiral separation ability of the capillary monolithic column, and the resolution reaches 7.34. Description of the drawings

[0039] In order to more clearly illustrate the technical solutions in the present invention or the prior art, the following will briefly introduce the drawings required for use in the description of the embodiments or the prior art.

[0040] Figure 1 It is a schematic diagram of the preparation process of L-His-ZIF-8@CMIP(rac-DCPP / PG-EDMA)@capillary;

[0041] Figure 2 It is a scanning electron micrograph of L-His-ZIF-8 (A), Vinyl-L-His-ZIF-8 (B) and L-His-ZIF-8@CMIP(rac-DCPP / PG-EDMA) (C) prepared outside the capillary column in Example 1;

[0042] Figure 3SEM image of L-His-ZIF-8@CMIP(rac-DCPP / PG-EDMA)@capillary in Example 1;

[0043] Figure 4 X-ray diffraction results of L-His-ZIF-8, Vinyl-L-His-ZIF-8, and L-His-ZIF-8@CMIP(rac-DCPP / PG-EDMA) prepared outside the capillary column in Example 1.

[0044] Figure 5 BET N2 adsorption-desorption isotherms of L-His-ZIF-8, Vinyl-L-His-ZIF-8, and L-His-ZIF-8@CMIP(rac-DCPP / PG-EDMA) prepared outside the capillary column in Example 1.

[0045] Figure 6 Pore size distribution diagrams of L-His-ZIF-8, Vinyl-L-His-ZIF-8, and L-His-ZIF-8@CMIP(rac-DCPP / PG-EDMA) prepared outside the capillary column in Example 1.

[0046] Figure 7 CEC chiral separation results of rac-DCPP by the capillary electrochromatography monolithic column in Example 1 and electrophoretograms of its single enantiomers (S-DCPP and R-DCPP).

[0047] Figure 8 Comparison of the chiral separation performance of CMIP(rac-DCPP / PG-EDMA) alone as the stationary phase in the capillary monolithic column, the capillary monolithic column with L-His-ZIF-8@NIP(PG-EDMA) prepared without a template as the stationary phase, and L-His-ZIF-8@CMIP(rac-DCPP / PG-EDMA)@capillary for 2,4-dichloropropionic acid in Example 1. Detailed implementation manners

[0048] To make the objectives, technical solutions, and advantages of the present invention clearer and more understandable, the present invention will be further described in detail below with reference to specific embodiments.

[0049] Example 1:

[0050] (1) The unmodified fused silica capillary with an inner diameter of 75 μm was rinsed with 1 M NaOH solution for 1 h, then rinsed with water until neutral, then rinsed with 1 M hydrochloric acid solution for 30 min, then rinsed with water until neutral, then rinsed with methanol for 30 min, dried with nitrogen, placed in an oven at 100 °C for 1 h, finally filled with a 50% (v / v) γ-MAPs methanol solution, the two ends were sealed, and placed in a water bath at 55 °C for reaction for 12 h. After the reaction, it was rinsed with methanol for 20 min and dried with nitrogen to obtain a vinyl-modified capillary;

[0051] (2) 0.6 mmol L-His was dissolved in 8 mL of water, and 50 μL of triethylamine was added and stirred for 5 min to obtain an L-His solution; 1.2 mmol of zinc nitrate hexahydrate and 4.2 mmol of 2-MM were respectively dissolved in 20 mL and 12 mL of methanol to obtain a zinc nitrate solution and a 2-MM solution; the L-His solution was mixed with the 2-MM solution, stirred for 15 min, then the zinc nitrate solution was added, and stirring was continued at room temperature for 24 h. After the reaction, it was washed several times with methanol and dried at 60 °C to obtain L-His-ZIF-8;

[0052] (3) 2 mg of L-His-ZIF-8 was dispersed in 2 mL of a 10% (v / v) GMA methanol solution, and stirring was continued at 55 °C for 6 h. After the reaction, it was washed several times with methanol and dried at 60 °C to obtain Vinyl-L-His-ZIF-8;

[0053] (4) 0.25 mmol of rac-DCPP and 1 mmol of PG were dissolved in 2 mL of a mixed solvent (V 乙醇： V 甲醇 = 3:2), stirred at room temperature for 30 min, then 4 mmol of EDMA was added, and stirred for 20 min to obtain a mixed solution; 2 mg of Vinyl-L-His-ZIF-8 was dispersed in 1 mL of the mixed solution, stirred for 5 min, 2 mg of AIBN was added, ultrasonicated for 30 min, and then blown with nitrogen for 5 min to obtain a Vinyl-L-His-ZIF-8 dispersion; finally, the Vinyl-L-His-ZIF-8 dispersion was filled into the vinyl-modified capillary, the two ends were sealed, and reacted at 70 °C for 4 h; after the reaction, it was rinsed with acetic acid / methanol (V 乙酸： V 甲醇 = 1:9) for 4 h to elute the template and unreacted reagents, and finally dried with nitrogen to obtain L-His-ZIF-8@CMIP(rac-DCPP / PG-EDMA)@capillary.

[0054] Similarly, without adding a template during the reaction and keeping other steps unchanged, L-His-ZIF-8@NIP(PG-EDMA)@capillary is obtained. Without adding Vinyl-L-His-ZIF-8 and keeping other steps unchanged, CMIP(rac-DCPP / PG-EDMA)@capillary is obtained. Transferring the reaction process of the premixed solution to a glass bottle allows the stationary phase powder L-His-ZIF-8@CMIP(rac-DCPP / PG-EDMA) to be obtained for characterization.

[0055] Example 2:

[0056] (1) A bare fused silica capillary with an inner diameter of 75 μm is rinsed with 1 M NaOH solution for 1 h, then rinsed with water until neutral, then rinsed with 1 M hydrochloric acid solution for 30 min, then rinsed with water until neutral, then rinsed with methanol for 30 min, dried with nitrogen, placed in an oven at 100 °C for 1 h, finally filled with a 50% (v / v) γ-MAPs methanol solution, sealed at both ends, and placed in a water bath at 55 °C for 12 h. After the reaction, it is rinsed with methanol for 20 min and dried with nitrogen to obtain a vinyl-modified capillary.

[0057] (2) Dissolve 0.6 mmol of L-His in 8 mL of water and add 50 μL of triethylamine and stir for 5 min to obtain an L-His solution. Dissolve 1.2 mmol of zinc nitrate hexahydrate and 4.2 mmol of 2-MM in 20 mL and 12 mL of methanol respectively to obtain a zinc nitrate solution and a 2-MM solution. Mix the L-His solution and the 2-MM solution, stir for 15 min, then add the zinc nitrate solution, and continuously stir at room temperature for 24 h. After the reaction, wash with methanol several times and dry at 60 °C to obtain L-His-ZIF-8.

[0058] (3) Disperse 2 mg of L-His-ZIF-8 in 2 mL of a 10% (v / v) GMA methanol solution and continuously stir at 55 °C for 6 h. After the reaction, wash with methanol several times and dry at 60 °C to obtain Vinyl-L-His-ZIF-8.

[0059] (4) Dissolve 0.25 mmol of rac-DCPP and 1 mmol of PG in 2 mL of a mixed solvent (V 乙醇： V 甲醇= 3:2), stir at room temperature for 30 min, then add 4 mmol of EDMA and stir for 20 min to obtain a mixed solution; disperse 4 mg of Vinyl-L-His-ZIF-8 in 1 mL of the mixed solution, stir for 5 min, add 2 mg of AIBN, ultrasonically treat for 30 min, and then blow with nitrogen for 5 min to obtain a Vinyl-L-His-ZIF-8 dispersion; finally, fill the vinyl-modified capillary with the Vinyl-L-His-ZIF-8 dispersion, seal both ends, and react at 70 °C for 4 h; after the reaction, rinse with acetic acid / methanol (V 乙酸： V 甲醇 = 1:9) for 4 h to elute the template and unreacted reagents, and finally dry with nitrogen to obtain L-His-ZIF-8@CMIP(rac-DCPP / PG-EDMA)@capillary.

[0060] Example 3:

[0061] (1) Rinse the unmodified fused silica capillary with an inner diameter of 75 μm with 1 M NaOH solution for 1 h, then rinse with water until neutral, then rinse with 1 M hydrochloric acid solution for 30 min, then rinse with water until neutral, then rinse with methanol for 30 min, and dry with nitrogen, then place in an oven at 100 °C for 1 h, finally fill with a 50% (volume fraction) γ-MAPs methanol solution, seal both ends, and place in a water bath at 55 °C for reaction for 12 h. After the reaction, rinse with methanol for 20 min and dry with nitrogen to obtain the vinyl-modified capillary;

[0062] (2) Dissolve 0.6 mmol of L-His in 8 mL of water, add 50 μL of triethylamine and stir for 5 min to obtain an L-His solution; dissolve 1.2 mmol of zinc nitrate hexahydrate and 4.2 mmol of 2-MM in 20 mL and 12 mL of methanol respectively to obtain a zinc nitrate solution and a 2-MM solution; mix the L-His solution and the 2-MM solution, stir for 15 min, then add the zinc nitrate solution, and continuously stir at room temperature for 24 h. After the reaction, wash with methanol several times and dry at 60 °C to obtain L-His-ZIF-8;

[0063] (3) Disperse 2 mg of L-His-ZIF-8 in 2 mL of a 10% (volume fraction) GMA methanol solution and continuously stir at 55 °C for 6 h. After the reaction, wash with methanol several times and dry at 60 °C to obtain Vinyl-L-His-ZIF-8;

[0064] (4) Dissolve 0.25 mmol of rac-DCPP and 1 mmol of PG in 2 mL of a mixed solvent (V 乙醇： V 甲醇In (3:2), stir at room temperature for 30 min, then add 2 mmol of EDMA and stir for 20 min to obtain a mixed solution; disperse 2 mg of Vinyl-L-His-ZIF-8 in 1 mL of the mixed solution, stir for 5 min, add 2 mg of AIBN, sonicate for 30 min, and then blow with nitrogen for 5 min to obtain a Vinyl-L-His-ZIF-8 dispersion; finally, fill the vinyl-modified capillary with the Vinyl-L-His-ZIF-8 dispersion, seal both ends, and react at 70 °C for 4 h; after the reaction, rinse with acetic acid / methanol (V 乙酸： V 甲醇 = 1:9) for 4 h to elute the template and unreacted reagents, and finally dry with nitrogen to obtain L-His-ZIF-8@CMIP(rac-DCPP / PG-EDMA)@capillary.

[0065] Performance test:

[0066] Apply the L-His-ZIF-8@CMIP(rac-DCPP / PG-EDMA)@capillary prepared in the example to the CEC chiral separation system for chiral separation of rac-DCPP. The specific CEC operation process and parameters are as follows:

[0067] Configuration of CEC buffer: Phosphate buffer, 20 mM, pH = 7.50;

[0068] Sample configuration: Prepare a rac-DCPP sample solution using a methanol / water (v / v = 1:1) mixture, 0.5 mg·mL -1 ;

[0069] Separation operation: Take the L-His-ZIF-8@CMIP(rac-DCPP / PG-EDMA)@capillary prepared in Example 1, with a length of 33 cm, burn a detection window of about 0.5 cm at 8.5 cm from one end, install it in the capillary cartridge, and carry out test operations on a capillary electrophoresis instrument (Agilent 3DCE 7100);

[0070] Injection (pressure injection): 30 mbar × 2 s, applied voltage is 20 kV, and detection wavelength is 210 nm;

[0071] Figure 2 The morphological characteristics of L-His-ZIF-8 (A), Vinyl-L-His-ZIF-8 (B), and L-His-ZIF-8@CMIP(rac-DCPP / PG-EDMA) (C) prepared outside the capillary column are shown. It can be seen that they are nanoparticles with relatively regular morphologies.

[0072] Figure 3 It is shown that L-His-ZIF-8@CMIP(rac-DCPP / PG-EDMA)@capillary is a capillary monolithic column with good porosity.

[0073] Figure 4 The XRD patterns of L-His-ZIF-8 (A), Vinyl-L-His-ZIF-8 (B) and L-His-ZIF-8@CMIP(rac-DCPP / PG-EDMA) are shown. The patterns of L-His-ZIF-8 and Vinyl-L-His-ZIF-8 are basically the same, indicating that the modification process of vinyl does not change the lattice characteristics of L-His-ZIF-8. However, in L-His-ZIF-8@CMIP, the positions of the diffraction peaks are basically the same, but the peak shapes change significantly because CMIP is amorphous and the CMIP(rac-DCPP / PG-EDMA) on the surface of L-His-ZIF-8 affects the XRD results.

[0074] Figure 5 In, the nitrogen adsorption isotherms of L-His-ZIF-8, Vinyl-L-His-ZIF-8 and L-His-ZIF-8@CMIP(rac-DCPP / PG-EDMA) all show typical type II adsorption characteristics, indicating that they are all typical mesoporous materials.

[0075] Figure 6 It is shown that in terms of pore size distribution, the pore size of L-His-ZIF-8 is The pore size of Vinyl-L-His-ZIF-8 is This slight difference in pore size is due to the bonding of GMA with L-His-ZIF-8. Due to the polymerization of CMIPs on the surface of Vinyl-L-His-ZIF-8, L-His-ZIF-8@CMIP(rac-DCPP / PG-EDMA) not only has the pore characteristics of L-His-ZIF-8, but also has a large number of pores, which are formed during the polymerization of CMIPs, indicating the successful synthesis of L-His-ZIF-8@CMIP(rac-DCPP / PG-EDMA) and the presence of a large number of micropore distributions.

[0076] Figure 7 It can be seen that L-His-ZIF-8@CMIP(rac-DCPP / PG-EDMA)@capillary can achieve chiral separation of rac-DCPP with a resolution of 7.34, reaching baseline separation. And the two sample peaks of rac-DCPP are attributed to R-DCPP and S-DCPP respectively.

[0077] In Figure 8 it, as a control, when CMIP(rac-DCPP / PG-EDMA)(without L-His-ZIF-8) and L-His-ZIF-8@NIP(PG-EDMA)(template-free) were used as the stationary phases, the resolution (Rs) of the corresponding CEC system for rac-DCPP was only 0.55 and 1.08, and baseline separation was not achieved, far less than that of L-His-ZIF-8@CMIP(rac-DCPP / PG-EDMA)@capillary (Rs = 7.34). This phenomenon is because although CMIP(rac-DCPP / PG-EDMA) has chiral resolution ability, when used alone as a CEC stationary phase, it is not sufficient to provide enough chiral recognition ability. And there are no specific recognition cavities of CMIPs in L-His-ZIF-8@NIP(PG-EDMA), only L-His-ZIF-8 plays a chiral recognition role. Therefore, the chiral resolution abilities of these two monolithic capillary columns are both weak. Correspondingly, L-His-ZIF-8@CMIP(rac-DCPP / PG-EDMA)@capillary has excellent chiral resolution ability because the synergistic effect between L-His-ZIF-8 with chiral recognition ability and CMIPs greatly improves the chiral resolution performance of L-His-ZIF-8@CMIP(rac-DCPP / PG-EDMA)@capillary. In addition, during the preparation of the monolithic capillary column, the ultra-large specific surface area of Vinyl-L-His-ZIF-8 provides a large number of binding sites, improving the loading amount of CMIP(rac-DCPP / PG-EDMA), and both Vinyl-L-His-ZIF-8 and the vinyl groups on the inner wall of the capillary can participate in the free radical polymerization reaction, greatly improving the stability of the monolithic capillary column. More importantly, L-His-ZIF-8 with a rigid framework can also reduce the deformation and collapse of the recognition cavities of CMIP(rac-DCPP / PG-EDMA).

[0078] Those of ordinary skill in the art should understand that the discussion of any of the above embodiments is only exemplary and is not intended to imply that the scope of the present invention is limited to these examples; under the concept of the present invention, the technical features in the above embodiments or different embodiments can also be combined, the steps can be implemented in any order, and there are many other variations in different aspects of the present invention as described above, which are not provided in detail for the sake of brevity.

Claims

1. A method for preparing a capillary electrochromatography monolithic column based on nanomaterials synthesized from chiral metal organic frameworks and chiral molecular imprinted polymers, characterized in that: The following steps are involved: (1) Capillary pretreatment: 3-(methacryloyloxy)propyltrimethoxysilane was used to modify the empty capillary to obtain a vinyl-modified capillary; (2) Preparation of L-His-ZIF-8: Dissolve L-His in water and add triethylamine to obtain an L-His solution, then dissolve zinc nitrate hexahydrate in methanol to obtain a zinc nitrate solution, then dissolve 2-MM in methanol to obtain a 2-MM solution; mix the L-His solution and the 2-MM solution, then add the zinc nitrate solution, stir to react, and after the reaction is completed, wash and dry to obtain L-His-ZIF-8; (3) Preparation of Vinyl-L-His-ZIF-8: Disperse L-His-ZIF-8 in a GMA solution, stir to react, and after the reaction is completed, wash and dry to obtain Vinyl-L-His-ZIF-8; (4) Preparation of a capillary electrochromatography monolithic column: First, a Vinyl-L-His-ZIF-8 dispersion is prepared using rac-DCPP, PG, EDMA, Vinyl-L-His-ZIF-8, AIBN and a mixed solvent; then, the Vinyl-L-His-ZIF-8 dispersion is filled into a vinyl-modified capillary, both ends are sealed, and the reaction is carried out. After the reaction is completed, the capillary column is rinsed with an eluent, and finally dried with nitrogen to obtain a capillary electrochromatography monolithic column.

2. The method for preparing a capillary electrochromatography monolithic column based on nanomaterials synthesized from chiral metal organic frameworks and chiral molecular imprinted polymers according to claim 1, characterized in that: The specification of the hollow capillary in the step (1) is an unmodified fused silica capillary with an inner diameter of 75 μm.

3. The method for preparing a capillary electrochromatography monolithic column based on nanomaterials synthesized from chiral metal organic frameworks and chiral molecular imprinted polymers according to claim 1, characterized in that: In the step (2), the molar ratio of zinc nitrate hexahydrate, L-His and 2-MM is 2:1:

7.

4. The method for preparing a capillary electrochromatography monolithic column based on nanomaterials synthesized from chiral metal organic frameworks and chiral molecular imprinted polymers according to claim 1, characterized in that: The GMA solution in step (3) is obtained by mixing GMA and methanol in a volume ratio of 1:

9.

5. The method for preparing a capillary electrochromatography monolithic column based on nanomaterials synthesized from chiral metal organic frameworks and chiral molecular imprinted polymers according to claim 1, characterized in that: In the step (3), the dosage ratio of L-His-ZIF-8 to GMA solution is 1 mg:1 mL.

6. The method for preparing a capillary electrochromatography monolithic column based on nanomaterials synthesized from chiral metal organic frameworks and chiral molecular imprinted polymers according to claim 1, characterized in that: In the step (4), the amount of rac-DCPP is 0.1-0.4 mmol, the amount of PG is 0.5-1.5 mmol, the amount of EDMA is 2-8 mmol, the amount of Vinyl-L-His-ZIF-8 is 1-5 mg, the amount of AIBN is 1-3 mg, and the amount of the mixed solvent is 1-5 mL.

7. The method for preparing a capillary electrochromatography monolithic column based on nanomaterials synthesized from chiral metal organic frameworks and chiral molecular imprinted polymers according to claim 1, characterized in that: The mixed solvent in step (4) is a mixture of ethanol and methanol in a volume ratio of 3:

2.

8. The method for preparing a capillary electrochromatography monolithic column based on nanomaterials synthesized from chiral metal organic frameworks and chiral molecular imprinted polymers according to claim 1, characterized in that: The preparation method of the Vinyl-L-His-ZIF-8 dispersion in the step (4) is as follows: first, rac-DCPP and PG are dissolved in a mixed solvent, stirred at room temperature for 30 minutes, and then EDMA is added and stirred for 20 minutes to obtain a mixed solution; Vinyl-L-His-ZIF-8 is dispersed in 1 mL of the mixed solution, stirred for 5 minutes, AIBN is added, ultrasonically treated for 30 minutes, and then nitrogen is blown for 5 minutes to obtain a Vinyl-L-His-ZIF-8 dispersion.

9. The method for preparing a capillary electrochromatography monolithic column based on nanomaterials synthesized from chiral metal organic frameworks and chiral molecular imprinted polymers according to claim 1, characterized in that: The eluent in step (4) is a mixture of acetic acid and methanol in a volume ratio of 1:

9.

10. The method for preparing a capillary electrochromatography monolithic column based on nanomaterials synthesized from chiral metal organic frameworks and chiral molecular imprinted polymers according to claim 1, characterized in that: In step (4), the time for washing the capillary column with the eluent is 4 hours.

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