Theoretical reassessment of Whelk-O1 as an enantioselective receptor for 1-(4-halogeno-phenyl)-1-ethylamine derivatives
Theoretical reassessment of Whelk-O1 as an enantioselective receptor for 1-(4-halogeno-phenyl)-1-ethylamine derivatives
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DOI：
10.1002/chir.20009
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发表时间：
2004-01-01
期刊：
影响因子：
2
通讯作者：
Roussel, C
中科院分区：
文献类型：
--
作者：
Del Rio, A;Hayes, JM;Roussel, C
结合分子力学和第一性原理计算，结合CHIRBASE数据库的实验数据，探讨了受体的对映体选择性。研究了Whelk-O1 HPLC手性固定相与一系列1-（4-卤代苯基）-1-乙胺衍生物外消旋物的相互作用。目的是从手性whelk - 01固定相和对映体之间的相互作用中提取信息，从而探索对映体选择行为的起源。计算正确地再现了洗脱顺序，合理地描述了实验对映选择性和保留因子。第一次洗脱的对映体复合物有不同的结合模式，而第二次洗脱的对映体复合物只有一种普遍的非对映体结合模式。采用天然键轨道（NBO）分析方法对整体最小键配合物进行了定量分析，以确定手性固定相与配体之间的供体-受体相互作用。分子间氢键是所研究的所有体系中必不可少的能量相互作用。CH-pi、芳香族堆积和各种电荷转移相互作用的量级较小，但对整体对映体选择行为仍然很重要。讨论了三点相互作用模型，指出了它在定性预测洗脱阶（绝对构型）中的困难。(C) 2004 Wiley-Liss, Inc。
A combination of molecular mechanics and first principles calculations was used to explore the enantioselectivity of receptors, taking into account experimental data from the CHIRBASE database. Interactions between the Whelk-O1 HPLC chiral stationary phase with the complete series of 1-(4-halogeno-phenyl)-1-ethylamine derivative racemates were studied. The objective was to extract information from the interactions between the chiral Whelk-O1 stationary phase and the enantiomers, hence probing the origin of the enantio selective behavior. Calculations correctly reproduce the elution orders and reasonably describe the experimental enantioselectivities and retention factors. Different binding modes were observed for the first eluted enantiomer complexes, whereas the second eluted show only one prevalent diastereomeric binding fashion. Natural bond orbital (NBO) analysis was used on the global minima bound-complexes to quantify donor-acceptor interactions among chiral stationary phase and ligand moieties. Intermolecular hydrogen bonding was found to be the essential energetic interaction for all systems studied. CH-pi, aromatic stacking and various charge transfer interactions were found to be smaller in magnitude but still important for the global enantio selective behavior. The three-point interaction model is discussed, pointing out the difficulty of its application for the qualitative prediction of elution orders (absolute configurations). (C) 2004 Wiley-Liss, Inc.