Molecular Imprinting Separation Technique

Molecular imprinting is a new and potential separation technique for preparing specialized recognition chromatography media. The process of the preparation consists of : (1) mixing the template molecules with monomers with appropriate functional groups, (2) low temperature and photo polymerization, and (3) extracting the template molecules from the polymer, which leaves cavities inside the polymers that are complementary in terms of size, shape, and functional group orientation to those of the template molecules. The technique has been applied widely in enantioselective separation for a variety of molecules, such as amino acids and their derivatives, free sugars, and racemic drugs. In this thesis, chiral separation of drugs and preparation of pueraria using molecular imprinting and imprinting of protein were studied. Molecular imprinting affinity model was established, and utilized to descript quantificationally imprinted separation.A chiral stationary phase for naproxen separation was prepared by molecular imprinting, in which cheap and simple acrylamide (functional monomer) and ethylene glycol dimethacrylate were copolymerised in the presence of template. The influences of several parameters on the resolution of racemic ketoprofen were investigated, including the amount of functional and cross-linking monomers, the molar ratio of the target molecule to the monomers, and so on. Evaluation of HPLC showed racemic naproxen was efficiently resolved on the molecular imprinting polymer. The effects of concentration of acetic acid in the mobile phase was studied and the polymers were able to separate naproxen from the structurally similar molecular such as ibuprofen and ketoprofen.A synthetic polymer for ketoprofen separation was first prepared by molecular imprinting, in which 4-vinylpyridine used as functional monomer and ethylene glycol dimethacrylate were copolymerised in the presence of template. Racemic ketoprofen was efficiently resolved on the MIPs, a selectivity factor of 1.52 and S-ketoprofen capacity factor of 9.52 were obtained. Furthermore, the polymer was able to separate ketoprofen from the structurally related ibuprofen and naproxen. Effect of several conditions on separation were optimized.The thermodynamic behaviour in the separation of molecular imprinting was studied. In the imprinted separation on naproxen and ketoprofen, the change of enthalpy and entropy was estimated, respectively. The results show that the values of A// and AS are negative and the AS is very small, which indicated the process of chiral separation for racemic ketoprofen and naproxen was controlled by enthalpy. Therefore, It was concluded that imprinted separation was mainly contributed to the functional group special interaction instead of spacial constructure. Surfacial constructre and shape of MIPs were studied, and pore size distribution of MIPs was investigated, which suggested percent of pore about 30nM is the most.It was assumed that a printed molecule was seen as a whole and monovalently bonded to the ligand, so an affinity chromatography model for molecular imprinting was first established. The data obtained on imprinted column of (5)-naproxen was simulated with the model, and a good agreement was obtained between the simulated and experimental data, which suggested that the affinity chromatography mechanism controlled the retention in this system. Moreover, the affinity chromatography equilibrium constants on (5^-naproxen in mobile phase of tetrahydrofuran-heptane and acetonitrile were 34.45 and 17.69, respectively. In addition, further demonstration about molecular imprinting affinity chromatography model was performed with (S)-ketoprofen imprinted column. The results showed a good agreement was obtained between the simulated and experimental data and the affinity chromatography equilibrium constant on (S)-ketoprofen was calculated to be 39.16 in mobile phase of acetonitrile in 22 C, and be in 28 C. Effect of temperature on affinity chromatography adsorption equilibrium constant of (S) -ketoprofen was investi...