Estrada E, Perdomo-López I, Torres-Labandeira J J
Faculty of Pharmacy, Department of Organic Chemistry, University of Santiago de Compostela, 15706 Santiago de Compostela, Spain.
J Chem Inf Comput Sci. 2001 Nov-Dec;41(6):1561-8. doi: 10.1021/ci0100402.
Quantitative models are found to describe the complexation of alpha- and beta-cyclodextrin with mono- and 1,4-disubstituted benzene derivatives by using combinations of 2D-, 3D-connectivity and quantum chemical molecular descriptors. The association constants (K(a)) for the inclusion complexation of cyclodextrins and benzene derivatives are calculated by the models found with a high degree of precision. These models also permit the interpretation of the driving forces of such complexation processes. In the case of the complexation of alpha-cyclodextrin with benzene derivatives these driving forces are mainly the electronic repulsion between frontier orbitals of the host and guest molecules. However, the complexation of beta-cyclodextrin with benzene derivatives is controlled by topological and topographic parameters indicating the relevance of the van der Waals and hydrophobic interactions. We also carried out molecular modeling studies showing that for alpha-cyclodextrin complexes the benzene ring is outside the cavity of the cyclodextrin, while in beta-cyclodextrin they penetrate deeply into the apolar and hydrophobic cavity of the host, which explain the differences in the driving forces for both complexation processes.
通过使用二维、三维连接性和量子化学分子描述符的组合，发现定量模型可描述α-和β-环糊精与单取代和1,4-二取代苯衍生物的络合作用。环糊精与苯衍生物包合络合的缔合常数（K(a)）由精度很高的模型计算得出。这些模型还允许解释此类络合过程的驱动力。在α-环糊精与苯衍生物的络合情况下，这些驱动力主要是主体和客体分子前沿轨道之间的电子排斥。然而，β-环糊精与苯衍生物的络合由拓扑和地形参数控制，表明范德华力和疏水相互作用的相关性。我们还进行了分子建模研究，结果表明对于α-环糊精络合物，苯环位于环糊精腔外部，而在β-环糊精中，它们深深穿透主体的非极性和疏水腔，这解释了两种络合过程驱动力的差异。
