A General Picture of Cucurbit[8]uril Host–Guest Binding

作者：Zhaoxi Sun, Zhe Huai, Qiaole He, Zhirong Liu · 发表于：Journal of Chemical Information and Modeling · 年份：2021 · DOI：10.1021/acs.jcim.1c01208 · 被引用次数：71 · 研究领域：Supramolecular Chemistry and Complexes、Crystallography and molecular interactions、Boron Compounds in Chemistry

Describing, understanding, and designing complex interaction networks within macromolecular systems remain challenging in modern chemical research. Host-guest systems, despite their relative simplicity in both the structural feature and interaction patterns, still pose problems in theoretical modeling. The barrel-shaped supramolecular container cucurbit[8]uril (CB8) shows promising functionalities in various areas, e.g., catalysis and molecular recognition. It can stably coordinate a series of structurally diverse guests with high affinities. In this work, we examine the binding of seven commonly abused drugs to the CB8 host, aiming at providing a general picture of CB8-guest binding. Extensive sampling of the configurational space of these host-guest systems is performed, and the binding pathway and interaction patterns of CB8-guest complexes are investigated. A thorough comparison of widely used fixed-charge models for drug-like molecules is presented. Iterative refitting of the atomic charges suggests significant conformation dependence of charge generation. The initial model generated at the original conformation could be inaccurate for new conformations explored during conformational search, and the newly fitted charge set improves the prediction-experiment correlation significantly. Our investigations of the configurational space of CB8-drug complexes suggest that the host-guest interactions are more complex than expected. Despite the structural simplicities of these mo...