Uniformly Sized Molecularly Imprinted Polymer for (S)-Nilvadipine. Comparison of Chiral Recognition Ability with HPLC Chiral Stationary Phases Based on a Protein

Abstract

Uniformly sized molecularly imprinted polymers (MIPs) for (S)-nilvadipine have been prepared by a multistep swelling and polymerization method using methacrylic acid, 2-(trifluoromethyl)acrylic acid, 2-vinylpyridine, or 4-vinylpyridine (4-VPY) as a functional monomer and ethylene glycol dimethacrylate (EDMA) as a cross-linker. The chiral recognition abilities of the MIPs for nilvadipine and other dihydropyridine calcium antagonists were evaluated using a mixture of sodium phosphate buffer (or water) and acetonitrile or only acetonitrile as the mobile phase. The (S)-nilvadipine-imprinted 4-VPY-co-EDMA polymers gave the highest resolution for nilvadipine among the MIPs prepared. In addition, the enantioseparation of nilvadipine was attained using the (S)-nilvadipine-imprinted EDMA polymers, without use of a functional monomer. 1H NMR and molecular modeling studies suggested a one-to-one hydrogen-bonding-based complex formation of (S)-nilvadipine with 4-VPY in chloroform. These results reveal that the (S)-nilvadipine-imprinted EDMA polymers could recognize the template molecule by its molecular shape, and that in addition to this recognition, hydrophobic and hydrogen-bonding interactions seems to play important roles in the retention and chiral recognition of nilvadipine on the 4-VPY-co-EDMA polymers in hydroorganic mobile phases. By optimizing chromatographic conditions such as column temperature and flow rate, the baseline separation of nilvadipine enantiomers was attained with a short analysis time and with a column efficiency comparable to commercially available chiral stationary phases based on a protein, such as ovomucoid or alpha1-acid glycoprotein.