A capillary electrochromatographic coated column based on iron-based cyclodextrin metal-organic frameworks and chiral molecularly imprinted polymers and its preparation method.

Abstract

This invention discloses a novel nanomaterial synthesized based on an iron-based cyclodextrin metal-organic framework and a chiral molecularly imprinted polymer. The iron-based cyclodextrin metal-organic framework is prepared via solvent diffusion using γ-cyclodextrin as the organic ligand and ferric nitrate as the metal salt. S-ofloxacin and (3-aminopropyl)triethoxysilane are dissolved in anhydrous ethanol, and the iron-based cyclodextrin metal-organic framework, tetraethoxysilane, and ammonia are added and mixed thoroughly. The mixture is reacted at room temperature. After the reaction, the mixture is filtered, washed with eluent, and dried to obtain the novel nanomaterial. This invention also discloses a capillary electrochromatography (CEC) coated column, which is prepared by fixing the aforementioned novel nanomaterial based on the iron-based cyclodextrin metal-organic framework and chiral molecularly imprinted polymer onto the inner wall of a capillary. The CEC coated column of this invention can be used in capillary electrochromatography systems to achieve efficient chiral resolution of the racemic drug ofloxacin.

Description

Technical Field

[0001] This invention belongs to the field of chemical synthesis and analysis technology, specifically relating to a novel nanomaterial based on iron-based cyclodextrin metal-organic frameworks and chiral molecularly imprinted materials, its synthesis method, a capillary electrochromatographic coated column using the nanomaterial as a coating, and its preparation method. Background Technology

[0002] Capillary electrochromatography (CEC) is a rapid and efficient column separation technique that uses a stationary phase within a capillary as the separation medium, combining the characteristics of high-performance capillary electrophoresis (HPCE) and high-performance liquid chromatography (HPLC). CEC is characterized by high selectivity and analytical efficiency, and is widely used in chiral resolution. The capillary column is the core of CEC, and its performance is directly affected by the composition and structure of the stationary phase. Capillary columns can be classified into coated columns, monolithic columns, and packed columns, among which coated columns are widely studied and applied due to their simple preparation and ease of modification. However, coated columns also have drawbacks such as low column capacity and weak chiral resolution. To overcome these shortcomings, researchers have modified the inner wall of capillary columns with nanomaterials such as gold nanoparticles, carbon nanotubes, and metal-organic frameworks through physical coating or chemical bonding to increase their specific surface area, ultimately improving the separation efficiency of the capillary column. In conclusion, developing capillary coated columns with excellent chiral resolution performance, high column efficiency, and ease of preparation is a crucial aspect of CEC development.

[0003] Metal-organic frameworks (MOFs) are porous crystalline nanomaterials formed by the self-assembly of metal ions / clusters and organic ligands, and have seen rapid development in recent years. MOFs have gained favor among researchers due to their ultra-high specific surface area, flexible and varied topologies, and uniformly tunable channels. Iron-based cyclodextrin metal-organic frameworks (Fe-CD-MOFs) are chiral metal-organic frameworks (CMOFs) that not only possess the inherent characteristics of MOFs but also are rich in chiral groups, thus exhibiting good chiral selectivity. Therefore, when CMOF nanomaterials prepared from cyclodextrin are used as capillary stationary phases, they can not only increase the specific surface area of ​​the capillary inner wall and improve its chiral resolution performance but also avoid the need to add chiral selectors to the buffer solution, reducing consumption. In previous studies, cyclodextrins and their derivatives have often been used as chiral selectors, but they often suffer from drawbacks such as unstable chiral separation performance and high consumption.

[0004] Polymers that use the interaction between a template and functional monomers, with a three-dimensional network structure formed by a cross-linking agent to fix their positions, and then remove the template to obtain cavities complementary to the template, are called molecularly imprinted polymers (MIPs). The cavities of MIPs exhibit high specificity for template recognition. After rapid development in recent decades, MIPs have been widely used in drug delivery, adsorption purification / separation, and sensor development. If the template is a chiral molecule, the resulting MIPs are chiral molecularly imprinted polymers (CMIPs) with chiral selectivity, which also hold an important position in the field of chiral separation.

[0005] In previous reports, both CMIPs and Fe-CD-MOF have been studied and applied in the field of chiral separation / selection. However, in CEC, the chiral resolution performance of capillary columns using Fe-CD-MOF and CMIPs as stationary phases alone is often unsatisfactory. When Fe-CD-MOF is used alone as a CEC stationary phase, it often suffers from poor chiral resolution, poor peak shape, and numerous interfering peaks; while when CMIPs is used alone as a CEC stationary phase, its chiral resolution capability rarely meets the requirements. To date, the inventors have not found any reports on CEC chiral resolution systems using novel nanomaterials synthesized from Fe-CD-MOF and CMIPs as stationary phases. The synthesis of this novel nanomaterial mainly faces the following challenges: on the one hand, sufficient CMIPs material is needed for the recognition of target molecules, while the porous structure of Fe-CD-MOF must not be completely masked; on the other hand, good dispersibility and particle size control of the nanomaterial must be maintained during the preparation process so that it can be well applied to the capillary stationary phase without clogging the capillary.

[0006] The issues of drug quality control and safe medication associated with chiral drugs have attracted great attention from pharmaceutical regulatory authorities in various countries. Establishing accurate, efficient, and sensitive methods for the separation and analysis of chiral drugs can provide effective approaches for the development of single-enantiomer new drugs and their pharmacodynamic and pharmacokinetic studies in living organisms, possessing significant application value and market potential. Summary of the Invention

[0007] The purpose of this invention is to address the technical problems of low chiral resolution and low separation efficiency of existing CEC coated columns by providing a novel nanomaterial synthesized based on iron-based cyclodextrin metal-organic frameworks (Fe-γ-CD-MOF) and chiral molecularly imprinted polymers (CMIPs), as well as a novel capillary electrochromatography coated column using this nanomaterial as a coating. This capillary electrochromatography coated column can be used to construct a CEC chiral resolution system and complete the chiral resolution of the chiral drug ofloxacin.

[0008] To achieve the above objectives, the specific technical solution adopted by the present invention is as follows:

[0009] A novel nanomaterial based on iron-based cyclodextrin metal-organic frameworks (Fe-γ-CD-MOF) and chiral molecularly imprinted polymers (CMIPs) is synthesized. The Fe-γ-CD-MOF is prepared via solvent diffusion using γ-cyclodextrin as the organic ligand and ferric nitrate as the metal salt. S-ofloxacin and (3-aminopropyl)triethoxysilane (APTES) are dissolved in anhydrous ethanol, and the Fe-γ-CD-MOF, tetraethoxysilane (TEOS), and ammonia are added and mixed thoroughly. The mixture is then reacted at room temperature. After the reaction is complete, the mixture is filtered, washed with an eluent, and dried to obtain the novel nanomaterial.

[0010] A method for synthesizing novel nanomaterials based on iron-based cyclodextrin metal-organic frameworks and chiral molecularly imprinted polymers, comprising:

[0011] Step (1) Preparation of iron-based cyclodextrin metal-organic framework (Fe-γ-CD-MOF): γ-cyclodextrin and ferric nitrate were dissolved in N,N-dimethylformamide (DMF), filtered, and placed in an open device; the open device was placed in a closed device containing methanol and incubated at room temperature for 24-48 h; the open device was removed and placed in a closed device containing hexadecyltrimethylammonium bromide solution and incubated at room temperature for 5-7 days; the crystals were filtered, washed by centrifugation with isopropanol, and dried to obtain Fe-γ-CD-MOF;

[0012] Step (2): S-ofloxacin and (3-aminopropyl)triethoxysilane (APTES) were dissolved in anhydrous ethanol and stirred at room temperature. Iron-based cyclodextrin metal-organic frameworks were added and stirred at room temperature. Tetraethoxysilane (TEOS) and ammonia were added while stirring and mixed evenly. The reaction was carried out at room temperature for 6 to 18 hours. After the reaction was completed, the mixture was filtered, washed with eluent, and dried to obtain a novel nanomaterial (Fe-CD-MOF@CMIP) synthesized based on iron-based cyclodextrin metal-organic frameworks and chiral molecularly imprinted polymers.

[0013] In step (1), the molar ratio of γ-cyclodextrin to ferric nitrate is 1:5 to 1:10, preferably 1:8.

[0014] The ferric nitrate mentioned is ferric nitrate nonahydrate.

[0015] The ratio of γ-cyclodextrin to N,N-dimethylformamide is 0.5:10 to 1.5:10 mmol / mL, preferably 1:10 mmol / mL.

[0016] Preferably, γ-cyclodextrin and ferric nitrate are dissolved in N,N-dimethylformamide after ultrasonic treatment, and the filter membrane used is an organic filter membrane with a diameter of 0.45 microns.

[0017] The open device can be a small beaker; the closed device can be a large beaker, and the large beaker is sealed with plastic wrap / sealing film.

[0018] The volume ratio of N,N-dimethylformamide to methanol is 1:50; the volume ratio of N,N-dimethylformamide to hexadecyltrimethylammonium bromide solution is 1:50.

[0019] The concentration of the hexadecyltrimethylammonium bromide solution is 0.32 g / L. The specific preparation method is as follows: dissolve 160 mg of hexadecyltrimethylammonium bromide in 500 mL of deionized water.

[0020] The centrifugal washing refers to washing the crystals prepared with 1 mmol of organic ligand with 20-40 mL of isopropanol each time, followed by centrifugation.

[0021] Preferably, the centrifugal washing refers to washing the crystals prepared with 1 mmol of organic ligand with 30 mL of isopropanol each time, followed by centrifugation.

[0022] The centrifugal washing is performed three times.

[0023] In step (2), the ratio of S-ofloxacin to anhydrous ethanol is 1:3 to 1:15 mg / mL, preferably 1:3 mg / mL.

[0024] The ratio of S-ofloxacin to (3-aminopropyl)triethoxysilane (APTES) is (1-5):(20-100) mg / μL, preferably 1:10-1:20 mg / μL, and more preferably 1:20 mg / μL.

[0025] The mass ratio of S-ofloxacin to iron-based cyclodextrin metal-organic framework is (1-5):(5-15), preferably 1:2-1:4, and more preferably 1:4.

[0026] The ratio of S-ofloxacin to tetraethoxysilane (TEOS) is (1-5):(25-100) mg / μL, preferably 1:10-1:20 mg / μL, and more preferably 1:20 mg / μL.

[0027] The ratio of S-ofloxacin to ammonia is (1-5):(25-100) mg / μL, preferably 1:10-1:20 mg / μL, and more preferably 1:20 mg / μL.

[0028] The ammonia solution has a mass fraction of 25% to 28%.

[0029] Specifically, S-ofloxacin and (3-aminopropyl)triethoxysilane are dissolved in anhydrous ethanol and stirred at room temperature for 20-40 minutes. Iron-based cyclodextrin metal-organic framework is added and stirred at room temperature for another 20-40 minutes. Then, while stirring, tetraethoxysilane and ammonia are added and mixed thoroughly.

[0030] More specifically, S-ofloxacin and (3-aminopropyl)triethoxysilane were dissolved in anhydrous ethanol and stirred at room temperature for 30 min. Iron-based cyclodextrin metal-organic frameworks were added and stirred at room temperature for another 30 min. Then, tetraethoxysilane and ammonia were added while stirring until homogeneous.

[0031] The eluent is a mixed solvent of methanol and acetic acid in a volume ratio of 9:1.

[0032] A capillary electrochromatography coated column based on a novel nanomaterial synthesized from iron-based cyclodextrin metal-organic frameworks and chiral molecularly imprinted polymers is described. The column is made by fixing the novel nanomaterial synthesized from iron-based cyclodextrin metal-organic frameworks and chiral molecularly imprinted polymers onto the inner wall of a capillary.

[0033] Preferably, the capillary electrochromatographic coated column is prepared by solvent diffusion of γ-cyclodextrin as an organic ligand and ferric nitrate as a metal salt to obtain an iron-based cyclodextrin metal-organic framework (Fe-γ-CD-MOF). S-ofloxacin and (3-aminopropyl)triethoxysilane (APTES) are dissolved in anhydrous ethanol, and the iron-based cyclodextrin metal-organic framework, tetraethoxysilane (TEOS), and ammonia are added and mixed evenly. The mixture is then flushed into an activated capillary, the two ends of the capillary are sealed, and the column is allowed to stand at room temperature. The capillary is then rinsed with eluent and dried with nitrogen to obtain the novel capillary electrochromatographic coated column.

[0034] A method for preparing a capillary electrochromatographic coated column based on novel nanomaterials synthesized from iron-based cyclodextrin metal-organic frameworks and chiral molecularly imprinted polymers includes:

[0035] Step (1), Capillary activation: The empty molten silica capillary is rinsed with sodium hydroxide solution, hydrochloric acid and methanol respectively, dried with nitrogen gas and dried at 110°C to obtain the activated capillary.

[0036] Step (2), Preparation of iron-based cyclodextrin metal-organic framework (Fe-γ-CD-MOF): Dissolve γ-cyclodextrin and ferric nitrate in N,N-dimethylformamide (DMF), filter, and place in an open device; place the open device in a closed device containing methanol and incubate at room temperature for 24-48 h; remove the open device and place it in a closed device containing hexadecyltrimethylammonium bromide solution and incubate at room temperature for 5-7 days; filter, wash the obtained crystals by centrifugation with isopropanol, and dry to obtain Fe-γ-CD-MOF;

[0037] Step (3): S-ofloxacin and (3-aminopropyl)triethoxysilane (APTES) are dissolved in anhydrous ethanol and stirred at room temperature. Iron-based cyclodextrin metal-organic framework is added and stirred at room temperature. Tetraethoxysilane (TEOS) and ammonia are added while stirring and mixed evenly. The mixture is then poured into an activated capillary, and both ends of the capillary are sealed. The capillary is allowed to stand at room temperature for 6-18 hours. The capillary is then rinsed with eluent and dried with nitrogen to obtain a novel capillary coated column Fe-CD-MOF@CMIP@capillary.

[0038] In step (1), the empty silica capillary is a molten silica capillary with an inner diameter of 75 micrometers without any modification.

[0039] The concentration of the sodium hydroxide solution is 1 mol·L⁻¹. -1 The concentration of the hydrochloric acid is 1 mol·L⁻¹. -1 .

[0040] Specifically, the activation of the capillary is as follows: the empty molten silica capillary is rinsed sequentially with sodium hydroxide solution, hydrochloric acid and methanol for 1 hour, 0.5 hours and 0.5 hours respectively, dried with nitrogen gas, and placed in an oven at 110°C for 1 hour to obtain the activated capillary, which is then stored at -4°C.

[0041] The capillary electrochromatographic coated column described in this invention can be efficiently applied to enantiomeric separation of chiral drugs / compounds and optical purity testing of active pharmaceutical ingredients.

[0042] Another object of the present invention is to provide the application of the capillary electrochromatographic coated column in the chiral resolution of racemic ofloxacin.

[0043] A method for chiral resolution of racemic ofloxacin based on capillary electrochromatography includes:

[0044] Running buffer: 5–30 mM phosphate buffer, pH 6.0–7.2;

[0045] Sample preparation: Racemic ofloxacin samples were prepared using a methanol-water (v / v = 1:1) mixture at a concentration of 0.5 mg / mL. -1 ;

[0046] Separation procedure: Take a 33cm long capillary electrochromatographic coated column with a detection window of about 0.5cm at 8.5cm on one end, insert the capillary cartridge, and carry out the experiment on a capillary electrophoresis instrument (Agilent 3D CE 7100);

[0047] Sample introduction method: 50mbar×2s, application voltage: 10kV, detection wavelength: 294nm.

[0048] The present invention has the following beneficial effects:

[0049] This invention presents a novel capillary electrochromatographic coated column with excellent chiral resolution, low cost, and good chemical stability. Compared with capillary coated columns using Fe-γ-CD-MOF and CMIPs alone as stationary phases, the Fe-CD-MOF@CMIP@capillary capillary coated column of this invention significantly improves the chiral resolution performance of racemic ofloxacin (resolution: 0 / 0.69→3.92), achieving a synergistic effect. Fe-γ-CD-MOF itself possesses a certain chiral recognition capability, which synergistically enhances the chiral resolution performance of the capillary coated column with CMIPs. The cross-linking effect of the molecularly imprinted polymer also improves the linkage stability of the stationary phase. The ultra-large specific surface area of ​​Fe-γ-CD-MOF greatly increases the loading capacity of CMIPs, and the rigid framework of Fe-CD-MOF can also prevent the collapse and deformation of the imprinted cavities of CMIPs.

[0050] The novel CEC chiral drug / compound resolution system, which uses Fe-CD-MOF and CMIPs as stationary phases, is highly innovative. Attached Figure Description

[0051] Figure 1 This is a schematic diagram of the preparation of Fe-CD-MOF@CMIP@capillary.

[0052] Figure 2 Transmission electron microscopy (TEM) images of Fe-CD-MOF(A) and Fe-CD-MOF@CMIP(B) in Example 1.

[0053] Figure 3 Scanning electron microscope images of an empty molten silica capillary column (A) and a Fe-CD-MOF@CMIP@capillary (B).

[0054] Figure 4 Electrophoresis results of racemic ofloxacin or S-ofloxacin on different capillary electrochromatographic coated columns are shown. Among them, A is the CEC chiral resolution result of racemic ofloxacin by Fe-CD-MOF@CMIP@capillary, B is the CEC chiral resolution result of S-ofloxacin by Fe-CD-MOF@CMIP@capillary, C is the CEC chiral resolution result of racemic ofloxacin by Fe-CD-MOF@capillary, and D is the CEC chiral resolution result of racemic ofloxacin by CMIP@capillary. Detailed Implementation

[0055] To better understand the present invention, the following embodiments are further illustrations of the invention. The descriptions below are illustrative and not restrictive, and should not be construed as limiting the scope of protection of the present invention.

[0056] Example 1

[0057] The preparation process of the capillary electrochromatographic coated column Fe-CD-MOF@CMIP@capillary is as follows: Figure 1 As shown, the steps are as follows:

[0058] Use 1 mol·L sequentially -1 Sodium hydroxide solution, 1 mol·L -1 The empty molten silica capillary (75 μm inner diameter) was rinsed with hydrochloric acid and methanol for 1 h, 0.5 h, and 0.5 h respectively, dried with nitrogen, and then dried in an oven at 110 °C for 1 h to obtain the activated capillary. It was then stored at -4 °C.

[0059] 1 mmol of γ-cyclodextrin and 8 mmol of ferric nitrate nonahydrate were dissolved in 10 mL of N,N-dimethylformamide (DMF) by sonication. The solution was filtered through a 0.45 μm organic filter and placed into a small beaker. The small beaker was then placed into a large beaker containing 500 mL of methanol. The large beaker was sealed with plastic wrap / sealing film and kept at room temperature for 24 h to allow the methanol to diffuse into the solution. The small beaker was then removed and placed into a large beaker containing 500 mL of cetyltrimethylammonium bromide solution (concentration: 0.32 g / L). The large beaker was sealed with plastic wrap / sealing film and incubated at room temperature for 5 days. The crystals were obtained by filtration, centrifugation and washing with isopropanol (30 mL × 3), and drying to obtain Fe-γ-CD-MOF.

[0060] 2.5 mg of S-ofloxacin and 50 μL of APTES were dissolved in 15 mL of anhydrous ethanol and stirred at room temperature for 30 min. Then, 10 mg of Fe-γ-CD-MOF was added, and stirring continued at room temperature for another 30 min. Subsequently, 50 μL of tetraethoxysilane (TEOS) and 50 μL of ammonia (mass fraction 25%–28%, the same below) were added while stirring, and the mixture was thoroughly combined. The reaction was carried out at room temperature for 12 h, filtered, and the capillary was washed with methanol-acetic acid (9:1, v / v) for two hours to obtain the novel nanomaterial Fe-CD-MOF@CMIP. Figure 2 It can be seen that, with Fe-γ-CD-MOF ( Figure 2 Compared to A), Fe-CD-MOF@CMIP ( Figure 2 The morphology of B) changed significantly, indicating that CMIPs were synthesized on Fe-CD-MOF.

[0061] 2.5 mg of S-ofloxacin and 50 μL of APTES were dissolved in 15 mL of anhydrous ethanol and stirred at room temperature for 30 min. Then, 10 mg of Fe-γ-CD-MOF was added, and stirring continued for another 30 min. Subsequently, 50 μL of tetraethoxysilane (TEOS) and 50 μL of ammonia were added while stirring, and the mixture was thoroughly mixed. This mixture was then poured into an activated capillary, and both ends of the capillary were sealed with rubber stoppers. The capillary was allowed to stand at room temperature for 12 h, then rinsed with methanol-acetic acid (9:1, v / v) for two hours and dried under nitrogen to obtain the novel capillary electrochromatographic coated column Fe-CD-MOF@CMIP@capillary. Figure 3 It can be seen that the inner wall of the empty molten silica capillary column is smooth and has no adhering material. Figure 3 A), while the attachment of the stationary phase can be clearly seen on the inner wall of Fe-CD-MOF@CMIP@capillary. Figure 3 B) indicates that Fe-CD-MOF@CMIP@capillary was successfully prepared.

[0062] Example 2

[0063] Use 1 mol·L sequentially -1 Sodium hydroxide solution, 1 mol·L -1 The empty molten silica capillary (75 μm inner diameter) was rinsed with hydrochloric acid and methanol for 1 h, 0.5 h, and 0.5 h respectively, dried with nitrogen, and then dried in an oven at 110 °C for 1 h to obtain the activated capillary. It was then stored at -4 °C.

[0064] 1 mmol of γ-cyclodextrin and 8 mmol of ferric nitrate nonahydrate were dissolved in 10 mL of N,N-dimethylformamide (DMF) by sonication. The solution was filtered through a 0.45 μm organic filter and placed into a small beaker. The small beaker was then placed into a large beaker containing 500 mL of methanol, and the large beaker was sealed with plastic wrap / sealing film and kept at room temperature for 24 h. The small beaker was then removed and placed into a large beaker containing 500 mL of cetyltrimethylammonium bromide solution (concentration: 0.32 g / L). The large beaker was sealed with plastic wrap / sealing film and incubated at room temperature for 5 days. The crystals were obtained by filtration, centrifugation and washing with isopropanol (30 mL × 3), and drying to obtain Fe-γ-CD-MOF.

[0065] 2.5 mg of S-ofloxacin and 50 μL of APTES were dissolved in 15 mL of anhydrous ethanol and stirred at room temperature for 30 min. 8 mg of Fe-γ-CD-MOF was added, and stirring was continued at room temperature for another 30 min. Then, while stirring, 50 μL of tetraethoxysilane (TEOS) and 50 μL of ammonia were added and mixed thoroughly. The mixture was then flushed into an activated capillary, and both ends of the capillary were sealed with rubber stoppers. The capillary was allowed to stand at room temperature for 12 h, and then flushed with methanol-acetic acid (9:1, v / v) for two hours. The capillary was then dried with nitrogen to obtain a novel capillary electrochromatographic coated column Fe-CD-MOF@CMIP@capillary.

[0066] Example 3

[0067] Use 1 mol·L sequentially -1 Sodium hydroxide solution, 1 mol·L -1 The empty molten silica capillary (75 μm inner diameter) was rinsed with hydrochloric acid and methanol for 1 h, 0.5 h, and 0.5 h respectively, dried with nitrogen, and placed in an oven at 110 °C for 1 h to obtain the activated capillary. It was then stored at -4 °C.

[0068] 1 mmol of γ-cyclodextrin and 8 mmol of ferric nitrate nonahydrate were dissolved in 10 mL of N,N-dimethylformamide (DMF) by sonication. The solution was filtered through a 0.45 μm organic filter and placed into a small beaker. The small beaker was then placed into a large beaker containing 500 mL of methanol, and the large beaker was sealed with plastic wrap / sealing film and kept at room temperature for 24 h. The small beaker was then removed and placed into a large beaker containing 500 mL of cetyltrimethylammonium bromide solution (concentration: 0.32 g / L). The large beaker was sealed with plastic wrap / sealing film and incubated at room temperature for 5 days. The crystals were obtained by filtration, centrifugation and washing with isopropanol (30 mL × 3), and drying to obtain Fe-γ-CD-MOF.

[0069] 5 mg of S-ofloxacin and 50 μL of APTES were dissolved in 15 mL of anhydrous ethanol and stirred at room temperature for 30 min. 10 mg of Fe-γ-CD-MOF was added and stirred at room temperature for another 30 min. Then, while stirring, 50 μL of tetraethoxysilane (TEOS) and 50 μL of ammonia were added and mixed thoroughly. The mixture was then flushed into an activated capillary, and both ends of the capillary were sealed with rubber stoppers. The capillary was allowed to stand at room temperature for 12 h, and then flushed with methanol-acetic acid (9:1, v / v) for two hours. The capillary was then dried with nitrogen to obtain a novel capillary electrochromatographic coated column Fe-CD-MOF@CMIP@capillary.

[0070] Comparative Example 1

[0071] Preparation of Fe-CD-MOF@capillary: Fe-CD-MOF was prepared by activating the capillary according to Example 1; 2 mg of Fe-CD-MOF was dispersed in 3 mL of anhydrous ethanol and poured into the activated capillary. The two ends of the capillary were sealed with rubber stoppers and allowed to stand at room temperature for 24 h; the capillary coated column with Fe-CD-MOF as the stationary phase was obtained, i.e., Fe-CD-MOF@capillary.

[0072] Comparative Example 2

[0073] Preparation of CMIP@capillary: The amount of Fe-CD-MOF added in Example 1 was adjusted to 0 mg / mL, while all other aspects remained the same as in Example 1, resulting in a capillary coated column with CMIPs as the stationary phase alone, i.e., CMIP@capillary.

[0074] Performance testing

[0075] The novel capillary electrochromatographic coated column prepared in Example 1 was applied to the CEC chiral resolution system to perform chiral resolution of the racemic drug ofloxacin. The specific CEC operation process and parameters are as follows:

[0076] Running buffer: 20 mM phosphate buffer, pH = 6.7;

[0077] Sample preparation: Racemic ofloxacin sample was prepared using a methanol-water (v / v = 1:1) mixture at a concentration of 0.5 mg / mL. -1 ;

[0078] Separation procedure: Take a 33cm capillary electrochromatographic coated column, burn out a detection window of about 0.5cm in length at 8.5cm from one end, insert the capillary cartridge, and carry out the experiment on a capillary electrophoresis instrument (Agilent 3D CE 7100);

[0079] Sample introduction method: 50 mbar × 2 s, application voltage: 10 kV, detection wavelength: 294 nm;

[0080] The resolution results of racemic ofloxacin on the novel capillary electrochromatographic coated column prepared in Example 1 are as follows: Figure 4 As shown, the novel capillary electrochromatography coated column Fe-CD-MOF@CMIP@capillary can achieve chiral separation of the racemic drug ofloxacin with a resolution of 3.92, achieving baseline separation. The capillary electrochromatography coated columns prepared in Examples 2 and 3 also achieved chiral separation of the racemic drug ofloxacin, achieving baseline separation. However, the resolutions of Fe-CD-MOF@capillary and CMIP@capillary for racemic ofloxacin were 0 and 0.69, respectively.

[0081] The above description is merely a preferred embodiment of the present invention and should not be construed as limiting the scope of the invention. Those skilled in the art can make modifications based on the above-described technical content without departing from the principles of the invention, and these modifications and variations are also considered within the scope of protection of the present invention.

Claims

1. A nanomaterial synthesized based on an iron-based cyclodextrin metal-organic framework and a chiral molecularly imprinted polymer, characterized in that: It is prepared by solvent diffusion method using γ-cyclodextrin as organic ligand and ferric nitrate as metal salt to obtain iron-based cyclodextrin metal-organic framework. S-ofloxacin and (3-aminopropyl)triethoxysilane are dissolved in anhydrous ethanol, and iron-based cyclodextrin metal-organic framework, tetraethoxysilane and ammonia are added and mixed evenly. The mixture is reacted at room temperature. After the reaction is completed, the mixture is filtered, washed with eluent, and dried to obtain nanomaterials. The molar ratio of γ-cyclodextrin to ferric nitrate is 1:5 to 1:10; the molar ratio of S-ofloxacin to (3-aminopropyl)triethoxysilane is (1-5):(20-100) mg / μL; the molar ratio of S-ofloxacin to tetraethoxysilane is (1-5):(25-100) mg / μL; and the mass ratio of S-ofloxacin to iron-based cyclodextrin metal-organic framework is (1-5):(5-15).

2. A method for synthesizing nanomaterials based on iron-based cyclodextrin metal-organic frameworks and chiral molecularly imprinted polymers as described in claim 1, characterized in that: include: Step (1) Preparation of iron-based cyclodextrin metal-organic framework: Dissolve γ-cyclodextrin and ferric nitrate in N,N-dimethylformamide, filter, and load into an open device; place the open device into a closed device containing methanol and incubate at room temperature for 24-48 h; remove the open device and place it into a closed device containing hexadecyltrimethylammonium bromide solution and incubate at room temperature for 5-7 days; filter, wash the obtained crystals by centrifugation with isopropanol, and dry to obtain iron-based cyclodextrin metal-organic framework; Step (2): S-ofloxacin and (3-aminopropyl)triethoxysilane were dissolved in anhydrous ethanol and stirred at room temperature. Iron-based cyclodextrin metal-organic framework was added and stirred at room temperature. Tetraethoxysilane and ammonia were added while stirring and mixed evenly. The reaction was carried out at room temperature for 6 to 18 hours. After the reaction was completed, the mixture was filtered, washed with eluent, and dried to obtain nanomaterials synthesized based on iron-based cyclodextrin metal-organic framework and chiral molecularly imprinted polymer.

3. The method for synthesizing nanomaterials based on iron-based cyclodextrin metal-organic frameworks and chiral molecularly imprinted polymers according to claim 2, characterized in that: In step (1), the ratio of γ-cyclodextrin to N,N-dimethylformamide is 0.5:10 to 1.5:10 mmol / mL; the concentration of the hexadecyltrimethylammonium bromide solution is 0.32 g / L.

4. The method for synthesizing nanomaterials based on iron-based cyclodextrin metal-organic frameworks and chiral molecularly imprinted polymers according to claim 2, characterized in that: In step (2), the ratio of S-ofloxacin to anhydrous ethanol is 1:3 to 1:15 mg / mL; the ratio of S-ofloxacin to ammonia is (1 to 5):(25 to 100) mg / μL; and the mass fraction of ammonia is 25% to 28%.

5. The method for synthesizing nanomaterials based on iron-based cyclodextrin metal-organic frameworks and chiral molecularly imprinted polymers according to claim 2 or 4, characterized in that: In step (2), the ratio of S-ofloxacin to (3-aminopropyl)triethoxysilane is 1:10 to 1:20 mg / μL; the ratio of S-ofloxacin to tetraethoxysilane is 1:10 to 1:20 mg / μL; and the ratio of S-ofloxacin to ammonia is 1:10 to 1:20 mg / μL.

6. The method for synthesizing nanomaterials based on iron-based cyclodextrin metal-organic frameworks and chiral molecularly imprinted polymers according to claim 2, characterized in that: In step (2), the mass ratio of S-ofloxacin to iron-based cyclodextrin metal-organic framework is 1:2 to 1:

4.

7. The method for synthesizing nanomaterials based on iron-based cyclodextrin metal-organic frameworks and chiral molecularly imprinted polymers according to claim 2, characterized in that: The eluent mentioned in step (2) is a mixed solvent of methanol and acetic acid in a volume ratio of 9:

1.

8. A capillary electrochromatographic coated column based on nanomaterials synthesized from iron-based cyclodextrin metal-organic frameworks and chiral molecularly imprinted polymers, characterized in that: It is a capillary electrochromatographic coated column made by fixing the nanomaterials based on iron-based cyclodextrin metal-organic frameworks and chiral molecularly imprinted polymers as described in claim 1 on the inner wall of a capillary.

9. A method for preparing a capillary electrochromatographic coated column as described in claim 8, characterized in that: include: Step (1), Capillary activation: The empty molten silica capillary is rinsed with sodium hydroxide solution, hydrochloric acid and methanol respectively, dried with nitrogen gas and dried at 110 ℃ to obtain the activated capillary. Step (2) Preparation of iron-based cyclodextrin metal-organic framework: Dissolve γ-cyclodextrin and ferric nitrate in N,N-dimethylformamide, filter, and place in an open device; place the open device in a closed device containing methanol and incubate at room temperature for 24-48 h; remove the open device and place it in a closed device containing hexadecyltrimethylammonium bromide solution and incubate at room temperature for 5-7 days; filter, wash the obtained crystals by centrifugation with isopropanol, and dry to obtain iron-based cyclodextrin metal-organic framework; Step (3): Dissolve S-ofloxacin and (3-aminopropyl)triethoxysilane in anhydrous ethanol, stir at room temperature, add iron-based cyclodextrin metal-organic framework, continue stirring at room temperature, then add tetraethoxysilane and ammonia while stirring, mix evenly, flush the mixture into an activated capillary, seal both ends of the capillary, let stand at room temperature for 6-18 h, then rinse the capillary with eluent, blow dry with nitrogen, and obtain a capillary coated column.

10. The application of the capillary electrochromatographic coated column of claim 8 in the chiral resolution of racemic ofloxacin.

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