| With the rapid development of the life sciences, environmental science, chemical industry and pharmaceutical industry, some complex systems have appeared, and raised new challenges for the separation and analysis technology, such as rapid analysis of chiral drug enantiomers. High performance liquid chromatography (HPLC) and capillary electrochromatography (CEC) are the most widely used and important means of potential chiral separation of drugs. Hence, the exploitation of a series of stable property, efficient, fast, well applied and low cost new stationary phases for HPLC and CEC are the crucial task in the fields of chromatographic separation science, synthetic chemistry, materials chemistry and supramolecular chemistry.In this paper, a novel isatin derivative of β-cyclodextrin (ISCDP) stationary phase was first prepared by using a ordered mesoporous SBA-15as bonded matrix. ISCDP has high separation selectivity and fast separation ability for chiral and achiral analytes, which attributed to the supramolecular interactions of isatin derivatized P-cyclodextrin and the low mass transfer resistance of SBA-15. The main work included the preparation and characterization of a isatin derivative of P-cyclodextrin ligand, a ordered mesoporous SBA-15and a new stationary phase (ISCDP); the chromatographic performance of new stationary phase for chiral and achiral analytes; the discussion of related separation mechanisms. Meanwhile, a open-tubular capillary electrochromatography column with nitro-derivatized P-cyclodextrin was also prepared and evaluated for CEC. As mentioned above, a series of chromatographic methods containing high performance liquid chromatography and electrochromatography were established for the rapid separation of5-fluorouracil compounds, three groups substituted benzene positional isomers, commonly used cardiovascular chiral drugs such as P-blockers and calcium channel blockers. The results showed that ISCDP has rapid separation abilities both chiral and achiraly drugs. Namely, a versatile column. The main contents are as follows:1. The recent advances on the preparation methods and applications of bonded silica gel stationary phases for HPLC was summerized. Meanwhile, it also involved in the related ordered mesoporous materials for chromatography and capillary electrochromatographic technique. Especially, the development of derivatized (3-CD chiral stationary phases (CSPs) and applications of capillary electrochromatography in the separation of chiral drugs were reviewed, respectively. All above that will contribute to the research basis of this thesis.2. A Schiff base of isatin derivatized β-cyclodextrin was synthesized by the condensation reaction between the carbonyl of isatin and ethylenediamino β-cyclodextrin. The Schiff base as ligand was bonded to homemade ordered mesoporous SBA-15via y-isocyanate propyltriethoxy silane coupling agent and obtained a new isatin derivative of β-cyclodextrin-bonded SBA-15stationary phase (ISCDP) for HPLC. Its chemical and physical parameters were characterized by infrared spectroscopy, mass spectrometry, elemental analysis, thermogravimetric analysis, scanning electron microscopy, transmission electron microscopy, X-ray diffraction and BET specific surface area analyzer. The hydrophobic and stereoselective chromatographic performance of ISCDP were investigated by using polar solute probes such as halogenated uracils, purines and positional isomers of disubstituted benzene. The results indicated that the indole ring of isatin on the β-CD stationary phase could enhance the separation selectivity to the above polar compounds in reversed-phase mode, which contributed the fast separation of8polar compounds within12min. The positional isomers of nitroaniline, aminophenol and benzenediol could be easily separated with a simple binary mobile phase. The the para-isomers were eluted finally, which was due to the inclusion interactions. The new isatin derived-p-CD stationary phase exhibited well separation ability because it could provide various sites besides hydrophobic interaction, such as hydrogen bonding, π-π effect and dipole-dipole interactions.3. The new stationary phase was successfully used to the enantioseparations of P-blockers and dansyl-amino acids in polar organic mode and reversed-phase mode, respectively. The chromatographic separation mechanisms were also discussed. The results showed that good separation effects of several chiral compounds on ISCDP were achieved within25min. According to the experimental results, we believe that the introduction of the isatin could improve the hydrophobic interaction ability of the cyclodextrin ligand in the above chromatography. And the isatin plane aromatic ring system also exhibited a stronger π-π interaction, which makes the chiral center of the drugs more easily close to or into the cyclodextrin cavity. In this way, the separation improvement contributs to the inclusion interaction of cyclodextrin Various synergistic forces help to enhance the chiral recognition ability of ISCDP, so as to achieve good effect of chiral separations.4. A new open-tubular capillary electrochromatography column with nitro derivatives of P-cyclodextrin (NO2-β-CD) was prepared by the ring-opening reaction of a coupling agent containing succinic anhydride and sol-gel technique. The chemical structure of new CEC column was characterized. The fundamental parameter of the electro-osmotic flow (EOF) was investigated. Some chiral separation conditions of several P-blockers and calcium channel blockers drugs were studied, including buffer solution, pH values, organic modifers, temperature, applied voltage and so on. The experimental results showed that the cyclodextrin-based column with electro-drawing NO2group exhibited fast separation ability to4basic blockers within15min under the optimized conditions. Cyclodextrin open-tubular column could be conveniently prepared. It can be used to establish rapid and environment-friendly chiral separation methods with low solvent consumption. |
PDF Full Text Request