Abstract
The quantum mechanics/molecular mechanics three-dimensional reference interaction site model (QM/MM/3D-RISM) method is a three-layer hybrid approach designed to calculate the electronic structure of complex molecules in solution. In this study, the QM/MM/3D-RISM method was employed to investigate electronic structure changes in ligand molecules upon molecular recognition by the macrocyclic host molecule cucurbit[7]uril (CB7). Thiabendazole (TBZ), a benzimidazole derivative, was selected as the ligand, which is known for its significant alterations in properties such as pKa, solubility, photostability, and fluorescence intensity upon binding to CB7. The calculations elucidated the mechanism underlying the changes in the electronic structure induced by encapsulation, as well as the role of solvation in these transformations.