Releasing Preferentially\nSequestered Na<sup>+</sup> from Its Confinement by Beauvericin: A\nSingle Water Molecule is\nthe Accomplice

Beauvericin (Bv) is a natural ionophore capable of transporting\nions across biological membranes. Mass spectrometry and infrared spectroscopy\nshow that Bv specifically captures sodium ions with a unique 6-fold\ncoordination in its cavity, which illustrates how ions are carried\nthrough the membrane. But with no reports on how ions are released\nfrom Bv at the interface, a complete picture of the ion transport\nprocess has yet to be established. In this study, conformational changes\nof Bv complexes with alkali metal ions upon hydration were investigated\nusing infrared spectroscopy and computational calculations. The addition\nof a single water molecule to Na<sup>+</sup>Bv pries the ion away\nfrom the 6-fold cavity to the amide face of the ionophore, evidence\nof the first step of ion release. In contrast, there is little impact\non the other M<sup>+</sup>Bv complexes, with the ion bound to the\nthree carbonyl groups on the amide face. Analysis of the carbonyl\nCO and water OH stretching modes reveals the competition between\nion–ionophore, ion–water, and water–ionophore\ninteractions and demonstrates how water actively participates in ion\ntransport by initiating ion release from the ionophore.