Theoretical Prediction And Regulation Of Molecularly Imprinted Polymer's Affinity And Selectivity

Molecularly imprinted polymer (MIP) is a new kind of macromolecular material with high molecular recognition characteristics. Owing to predetermined property with specific recognition capability and wide practicability, it has been developed quickly in recent years. MIP is also called synthetic antibody. However, compared with natural antibody, MIP can be easily prepared in large quantities and it also showed much higher stability even under extreme conditions. For these reasons, many studies have been focused on the application of MIP in chromatographic separation, solid phase extraction, biosensors, antibody mimicking and catalyzing reactions. While the practical study has made substantial progress the theoretical study is relatively insufficient and the recognition mechanism remains to be further understood. In addition, the time required for the design, synthesis to evaluation and application of a MIP is still a long and tedious task, which greatly limited its commercialization. A thorough review of general theory and application of MIP was conducted in the first chapter. The review showed that the study of molecular recognition mechanism of MIP is insufficient; the cycle from design and preparation to evaluation and application of a MIP was too long. Furthermore, some simple small molecules and molecules containing intramolecular hydrogen bond had poor imprintogenicity (the potential of a template to be imprinted) and were difficult to be imprinted. Based on the review and the previous work of our group, the research target of the present dissertation was proposed. Simply speaking, the first aim was to establish a systematic computational chemistry-based theoretical model to guide MIP preparation and to predict the affinity and selectivity of a MIP. And the second aim was to imprint templates of poor imprintogenicity by an indirect (or regulated) approach. The main conclusions and original aspects of the present dissertation are summarized as follows: Two MIP systems were systematically studied by the computer simulation and the theoretical model for the prediction of affinity and selectivity of MIP was established, which could commendably simulate the pre-organization of template and functional monomer, polymerization, elution of template and rebinding of template or its analogues. The accuracy of the theoretical prediction was investigated with molecular mechanics method, semi-emperical method including CNDO, AM1 and PM3, and ab-initio method. The results showed that PM3 and ab-initio methods were more suitable for the simulation of the MIP system. The systematic investigation on nicotinamide and p-hydroxybenzoic acid MIP systems showed that the theoretically predicted affinity and selectivity were in good agreement with the experimental ones. Namely, the interaction energy between the template and the functional monomer had a positive correlation with its retention (capacity factor) on related MIP packed cartridge. The above proposed computational model was further applied in the selection of suitable functional monomer for a given template, in the optimization of monomer-template ratio and in the choice of proper porogen. The study was carried out with nicotinamide as template, methacrylic acid, acrylic acid, 4-vinyl pyridine, styrene, acrylamide, or acrylonitrile as functional monomer and toluene, acetonitrile, chloroform or methanol as porogen. Three conclusions could be drawn based on theoretical prediction with solvent effect and mass balance of template-monomer interaction in pre-organization stage included. (1) Selection of the functional monomer with the largest interaction energy for a given template was in favor of obtaining MIP with high affinity and selectivity. (2) To get more accurate result in theoretical calculation the solvent effect should be included. For aprotonic porogens (such as toluene, chloroform, acetonitrile) dielectric constants should be considered while for protic porogens (such as methanol) both the dielectric constant and hydrogen bonding interference of the...