Ion Recognition beyond Size Matching: Cooperative Hydration Effect on the K + Selectivity of Valinomycin over Na + Revealed by Cryogenic Double Ion Trap Infrared Spectroscopy.

The naturally occurring ionophore valinomycin (VM) selectively transports K + across the biological membrane, which makes VM a plausible antivirus and antibacterial candidate. The K + selectivity of VM was rationalized based on a size-matching model despite structural inconsistency between experiments and computations. In this study, we investigated the conformations of the Na + VM complex with 1-10 water molecules using cryogenic ion trap infrared spectroscopy with computational calculations. It shows that the water molecule penetrates the cavity of VM deeply enough to distort the C 3 -symmetric structure of gas-phase Na + VM, in stark contrast to hydrated clusters of K + VM with C 3 -symmetric structure, where H 2 O is located outside the cavity. The high affinity to K + would be ascribed to minimal hydration-induced structural deformation of K + VM compared to Na + VM. This study highlights a novel cooperative hydration effect on the K + selectivity and will provide an updated understanding of its ionophoric properties beyond the traditional size-matching model.