Modulation of the Intermolecular Interactions of Cucurbit7uril with Phenylalanine Derivatives by the Functional Groups

Abstract Intermolecular interactions in 1:1 inclusion complexes of cucurbit7uril (CB7) with phenylalanine derivatives were investigated by density functional theory (B97-D) calculations. For each complex, 2 optimized geometries were found: conformer C in which a guest molecule resided in the center of CB7, and conformer E where a guest molecule was present at the edge of CB7. The order of energy differences between these conformers agreed well with previously reported differences in the affinity of guest molecules for CB7. Molecular dynamics simulations of the complexes showed that the guest molecules in CB7 had different stabilities, and the calculated binding free energies between them also qualitatively agreed with the experimental results. Pair-interaction energy decomposition analyses of the complexes at FMO-MP2/6-31G(d) and aug-cc-pVDZ level of theory were performed using snapshot structures at 500 ns of simulations. The dispersion interaction characterized the interaction, and the order of total interaction energies between the guest molecules and CB7 was also associated with the experimental results. A significant difference in electrostatic interaction energies was observed in conformer E, which was correlated with the stability of the guest molecules at the edge of CB7. The balance between the stabilities of these conformers was correlated with the affinity of guest molecules for CB7.