Uniformly sized molecularly imprinted polymer for (S)-nilvadipine.: Comparison of chiral recognition ability with HPLC chiral stationary phases based on a protein
Uniformly sized molecularly imprinted polymer for (S)-nilvadipine.: Comparison of chiral recognition ability with HPLC chiral stationary phases based on a protein
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DOI：
10.1021/ac026039z
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发表时间：
2003-01-15
影响因子：
7.4
通讯作者：
Haginaka, J
中科院分区：
文献类型：
--
作者：
Fu, Q;Sanbe, H;Haginaka, J
以甲基丙烯酸、2-（三氟甲基）丙烯酸、2-乙烯基吡啶或4-乙烯基吡啶（4-VPY）为功能单体，乙二醇二甲基丙烯酸酯（EDMA）为交联剂，采用多级溶胀和聚合的方法制备了(S)-尼伐地平均匀尺寸的分子印迹聚合物（MIPs）。使用磷酸钠缓冲液（或水）和乙腈或仅乙腈作为流动相，评估了MIPs对尼伐地平和其他二氢吡啶钙拮抗剂的手性识别能力。在所制备的mip中，(S)-尼伐地平印迹的4- vy -co- edma聚合物具有最高的尼伐地平分辨率。此外，在不使用功能单体的情况下，利用(S)尼伐地平印迹EDMA聚合物实现了尼伐地平的对映体分离。H-1核磁共振和分子模型研究表明，(S)-尼伐地平与4-VPY在氯仿中形成一对一的氢键配合物。这些结果表明，(S)-尼瓦地平印迹EDMA聚合物可以通过其分子形状识别模板分子，并且除了这种识别外，疏水和氢键相互作用似乎在尼瓦地平在4- vy -co-EDMA聚合物的水有机流动相上的保留和手性识别中起重要作用。通过优化色谱条件（如柱温和流速），在较短的分析时间内获得了尼伐地平对映体的基线分离，柱效率与基于蛋白质（如卵泡样蛋白或α(1)-酸性糖蛋白）的市售手性固定相相当。
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 enantio-separation of nilvadipine was attained using the (S)nilvadipine-imprinted EDMA polymers, without use of a functional monomer. H-1 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 alpha(1)-acid glycoprotein.