Abstract
Changes in mechanical stresses in a tight-binding host-guest system were computed and visualized as the cationic was computationally pulled out of the cucurbituril host in a series of steps. A sharp conformational transition was observed as one of the guest's ammonium groups jumped through the center of the host to the opposite portal. The conformation immediately prior to this transition was found to possess high levels of Lennard-Jones and electrostatic stress. This observation, along with the specific distribution of Lennard-Jones stress around the portals, suggested that the conformational transition resulted from steric constriction, which had been expected, and electrostatics, which was not expected. An important role for electrostatics, at least at the level of these calculations, was confirmed by a comparative computational pulling study of another guest molecule lacking the critical ammonium group. These calculations suggest that the binding kinetics of diammonium guests that position an ammonium at each cucurbituril portal will be found to be slower than the kinetics of monoammonium guests. More generally, the results suggest that computational stress analysis can provide mechanistic insight into supramolecular systems. It will be of considerable interest to extend such applications to biomolecules, for which the mechanisms of conformational change are of great scientific and practical interest.