Releasing Preferentially Sequestered Na⁺ from Its Confinement by Beauvericin: A Single Water Molecule is the...

Beauvericin (Bv) is a natural ionophore capable of transporting ions across biological membranes. Mass spectrometry and infrared spectroscopy show that Bv specifically captures sodium ions with a unique 6-fold coordination in its cavity, which illustrates how ions are carried through the membrane. But with no reports on how ions are released from Bv at the interface, a complete picture of the ion transport process has yet to be established. In this study, conformational changes of Bv complexes with alkali metal ions upon hydration were investigated using infrared spectroscopy and computational calculations. The addition of a single water molecule to Na⁺Bv pries the ion away from the 6-fold cavity to the amide face of the ionophore, evidence of the first step of ion release. In contrast, there is little impact on the other M⁺Bv complexes, with the ion bound to the three carbonyl groups on the amide face. Analysis of the carbonyl C═O and water OH stretching modes reveals the competition between ion-ionophore, ion-water, and water-ionophore interactions and demonstrates how water actively participates in ion transport by initiating ion release from the ionophore.