Environmental Engineering and Toxicology Department, Catholic University of San Antonio, Guadalupe, Murcia, C.P. 30107, Spain.
J Pharm Sci. 2009 Dec;98(12):4557-76. doi: 10.1002/jps.21747.
This study aims at developing a quantitative structure-property relationship (QSPR) model for predicting complexation with beta-cyclodextrins (beta-CD) based on a large variety of organic compounds. Molecular descriptors were computed following the TOPological Substructural MOlecular DEsign (TOPS-MODE) approach and correlated with beta-CD complex stability constants by linear multivariate data analysis. This strategy afforded a final QSPR model that was able to explain around 86% of the variance in the experimental activity, along with showing good internal cross-validation statistics, and also good predictivity on external data. Topological substructural information influencing the complexation with beta-CD was extracted from the QSPR model. This revealed that the major driving forces for complexation are hydrophobicity and van der Waals interactions. Therefore, the presence of hydrophobic groups (hydrocarbon chains, aryl groups, etc.) and voluminous species (Cl, Br, I, etc.) in the molecules renders easy their complexity with beta-CDs. To our knowledge, this is the first time a correlation between TOPS-MODE descriptors and complexing abilities of beta-CDs has been reported.
本研究旨在基于大量有机化合物开发一种预测与β-环糊精（β-CD）络合的定量结构-性质关系（QSPR）模型。采用拓扑结构分子设计（TOPS-MODE）方法计算分子描述符，并通过线性多元数据分析将其与β-CD 络合稳定常数相关联。该策略提供了一个最终的 QSPR 模型，能够解释实验活性的约 86%的方差，同时显示出良好的内部交叉验证统计数据，以及对外部数据的良好预测性。从 QSPR 模型中提取了影响与β-CD 络合的拓扑亚结构信息。这表明，疏水作用和范德华相互作用是络合的主要驱动力。因此，分子中存在疏水性基团（碳氢链、芳基等）和大体积物质（Cl、Br、I 等），使得它们很容易与β-CDs 络合。据我们所知，这是首次报道 TOPS-MODE 描述符与β-CD 络合能力之间的相关性。
