COMPUTATIONAL DESIGN OF A HIGH SELECTIVE MOLECULARLY IMPRINTED POLYMER FOR SOLID-PHASE EXTRACTION OF CHENODEOXYCHOLIC ACID FROM CRUDE BILE

This work has focused on the rational development of polymers capable of acting as traps of Chenodeoxycholic acid. Computational modeling was combined with molecular imprinting technology to obtain networks with high affinity for Chenodeoxycholic acid in aqueous medium. We use the density functional theory (DFT) at M062x/6-31g^*+(d, P) level and Gaussian 2009 package to select of 10 monomers, which are commonly used for imprinted networks. The effect of polymerization solvent was also evaluated by the polarizable continuum model(PCM), which was chosen based on the comparison of the binding energy of the complexes between the template and functional monomers in different polymerization solvents. The computational method showed that the three fluoromethyl acrylic acid had the highest stabilization energy for the pre-polymerization adducts. Additionally, the mole ratio of 1:4 give the highest△E . Due to the functional monomer dimerization in the molecular imprinting process, in order to get a suitable template to functional monomer molar ratio for MIP preparations, eight different polymers were prepared using Chenodeoxycholic acid as the template. The MIPs were synthesized in a non-covalent approach via thermal free-radical polymerization, using two different polymerization methods, emulsion and suspension. Batch rebinding experiments were performed to evaluate the binding properties of the imprinted polymers. The best results were obtained with a MIP prepared using suspension polymerization with three fluoromethyl acrylic acid as the functional monomer and ethylene glycol dimethacrylate (EGDMA)as the crosslinker with a molar ratio of 1:6:20. Compared to polymers prepared without functional monomer, both imprinted and non-imprinted microparticles showed a high capability to extract Chenodeoxycholic acid from aqueous medium. The adsorption experiments revealed that MMIP showed better extraction capacity and selectivity toward Chenodeoxycholic acid and its analogues than the non-imprinted polymer(NIP). The MMIP possessed adsorption capacity of 140mg/g for Chenodeoxycholic acid and the imprinting factor was 2.10 at separate adsorption and 1.87 at competitive adsorption.