Realizing Molecular Recognition And High Efficient Preparation For Enantiomers Of Chiral Drugs By Constituting Chiral Caves With Novel Surface-molecular Imprinting Technique

Chiral drugs in the large proportion of drugs in natural and synthetic drugs, there are many chiral compounds, the enantiomers of pharmacological activity and toxicity are often very different, sometimes even the nature of the opposite. Therefore, separation and determination of chiral drugs, the study of the pharmacokinetics of chiral drugs dynamics to determine the kinetic parameters of drugs, pharmacological and toxicological mechanisms and quality control of chiral drugs are all of great significance. Then, the molecular imprinting towards the grafted PMAA was performed with one enantiomer of tetramisole (TM), L-TM, as template molecule and using the novel surface-molecular imprinting technique established by our research group, and the L-TM molecule-imprinted material MIP-PMAA/SiO₂ was prepared. And to explore the imprinted materials of racemic D, L-TM in the separation of two enantiomers of the performance.To the molecular surface imprinted materials used in separation and purification of chiral drugs are discussed studies, the results of this study for separation of chiral drugs to enhance technology have important scientific significance and value.using the novel surface-molecular imprinting technique, the coupling agentγ-aminopropyltrimethoxysilane (AMPS) was bond onto the surface of silica gel particles, obtaining the modified particles AMPS-SiO₂. A redox initiating system was constructed by the amino groups on AMPS-SiO₂ and ammonium persulphate in the solution, and the surface-initiated graft polymerization of methacrylic acid (MAA) on the silica gel particles was realized, preparing the grafted particles PMAA/SiO₂ with high grafting degree (30g/100g). the effects of different factors on the surface- initiated graft polymerization were investigated in depth. The experimental results show that for the surface-initiated graft polymerization system, the suitable temperature is 40℃. If the temperature is over 40℃, the graft polymerization will be affected, and the grafting degree of PMAA will decline because of the heat decomposition of ammonium persulphate. During the graft polymerization, the grafted polymer layer which has formed is a hindrance to the subsequent graft polymerization. the used amount of initiator and the monomer concentration affect the graft polymerization intensively. The appropriate reaction conditions are as follows: a used amount of 1.1% for the initiator in the solution (it implies the mass percent of the monomer) and a monomer concentration of about 5% (it drives at the mass percent of the solution).More in-depth study of four grafted particles PMAA/SiO₂ and mechanism of adsorption of imidazole. The results show that, PMAA/SiO₂ of the Tetramisole, adsorption driving force is the role of hydrogen bonding and electrostatic interactions of two synergistic results. In the pH = 8, PMAA/SiO₂ with the largest of the four imidazole adsorption. Temperature on the adsorption performance is also greatly affected the adsorption capacity decreased with increasing temperature.Finally, the molecular imprinting towards the grafted PMAA was performed with one enantiomer of tetramisole (TM), L-TM, as template molecule and ethylene glycol diglycidyl ether (EGDE) as crosslinking agent by using the novel surface-molecular imprinting technique established by our research group, and the L-TM molecule- imprinted material MIP-PMAA/SiO₂ was prepared. With another enantiomer, D-TM as a contrast compound, both static and dynamic methods were adopted to study the chiral recognition character and binding property of MIP-PMAA/SiO₂ for L-TM and to examine its ability to separate the two enantiomers in raceme. The experiment results show that MIP-PMAA/SiO₂ have specific recognition selectivity and excellent binding affinity for L-TM, and its the selectivity coefficient for L-TM with respect to D-TM reaches 4.03, displaying fine ability to separate the two enantiomers. Besides, MIP-PMAA/SiO₂ has excellent elution property, and with a diluted aqueous solution of NaOH as the eluent, the desorption ratios of L-TM 99.08 % in 20 BV.