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.

Separation of Inorganic Anions on a Pyridine Stationary Phase in Ion Chromatography

“…6 2-Vinylpyridine and 4-vinylpyridine were used as a functional monomer to prepare uniformly sized molecularly imprinted polymers for chiral recognition of nilvadipine and other dihydropyridine calcium antagonists using a mixture of sodium phosphate buffer (or water) and acetonitrile or only acetonitrile as the mobile phase. 7 The present paper investigates the retention behavior of inorganic anions on a pyridine stationary phase commercially available for hydrophilic interaction chromatography (HILIC) in ion chromatography.…”

Preparation and evaluation of uniform-sized molecularly imprinted polymer beads used for the separation of sulfamethazine

“…However, this method is complex and time-consuming, since three steps are usually needed in the swelling process, i.e. the activation of the seed polystyrene formed by emulsifier-free emulsion polymerization, the absorption of porogen and initiator and the absorption of the template molecule, functional monomer and cross-linking monomer (Fu et al, 2003). Therefore, it is necessary to search other simpler methods for manufacturing this material.…”

Retentivity and Enantioselectivity of Uniformly-sized Molecularly Imprinted Polymers for (S)-Nilvadipine in Aqueous and Non-Aqueous Mobile Phases

“…To overcome this problem, the MIPs, which give uniformly-sized and monodispersed particles, have been prepared using a multi-step swelling and polymerization method. 9 The MIPs prepared by this method have been applied for chiral separations of drugs, 10,11 and on-line extractions of drugs 12 and environmental pollutants 13 using aqueous mobile phases. This is because the use of aqueous mobile phases is desirable for the biomedical and environmental applications.…”

“…Recently, we prepared the MIP for (S)-nilvadipine, and indicated that the MIP for (S)-nilvadipine had a column efficiency in aqueous mobile phases comparable to those of commercially available chiral stationary phases based on a protein, such as ovomucoid or α1-acid glycoprotein. 11 However, it is thought that specific interactions such as hydrogen-bonding and/or electrostatic interactions could be hampered in aqueous environments. 14 In this study, uniformly-sized (S)-nilvadipine-imprinted polymers were prepared by a multi-step swelling and polymerization method using methacrylic acid (MAA) or 4-vinylpyridine (4-VPY) as a functional monomer, ethylene glycol dimethacrylate (EDMA) as a cross-linker, and toluene, chloroform, cyclohexanol or phenylacetonitrile as a porogen.…”