Schefzick S, Lämmerhofer M, Lindner W, Lipkowitz K B, Jalaie M
Department of Analytical Chemistry, University of Vienna, Vienna, Austria.
Chirality. 2000 Nov;12(10):742-50. doi: 10.1002/1520-636X(2000)12:10<742::AID-CHIR7>3.0.CO;2-M.
A comparative molecular field analysis (CoMFA) was carried out on a set of aligned quinine-based stationary phase molecules used in enantioselective chromatography. The best QSAR derived has a cross-validated (predictive) r(2)(cv) = 0.671 and a normal r(2) = 0.998. For CoMFAs using both steric and electrostatic fields as descriptors, the steric field descriptors explained more than 91% of the variance while the electrostatic descriptors explained less than 9% of the variance. It is concluded that the long-range electrostatic potential surrounding the positively charged CSPs are not enantiodiscriminating, while the van der Waals and local electrostatic surface features of these CSPs are highly discriminating. Quantum mechanical calculations back up this claim by showing a relatively symmetric electrostatic iso-contour surface. From the QSAR derived here, a region around the carbamate moiety was located where placement of steric bulk is predicted to enhance chiral discrimination. A set of possible synthetic target molecules is presented.
对一组用于对映体选择性色谱的基于奎宁的固定相分子进行了比较分子场分析（CoMFA）。所得最佳定量构效关系（QSAR）的交叉验证（预测性）r²(cv) = 0.671，常规r² = 0.998。对于使用空间场和静电场作为描述符的CoMFA，空间场描述符解释了超过91%的方差，而静电描述符解释的方差不到9%。得出的结论是，带正电荷的固定相周围的长程静电势没有对映体区分能力，而这些固定相的范德华力和局部静电表面特征具有高度区分能力。量子力学计算通过显示相对对称的静电等轮廓表面支持了这一说法。从这里得出的QSAR中，确定了氨基甲酸酯部分周围的一个区域，预测在该区域放置空间体积将增强手性区分能力。给出了一组可能的合成目标分子。
