The Path from Sequestration to Hydration: Why Na⁺ Takes a Unique Route with the Ionophore, Beauvericin

Previous investigations of the ionophore, beauvericin, have shown that Na⁺ is uniquely sequestered, with a 6-fold coordination involving the oxygens from six carbonyl groups, three amides and three esters. The coordination of the remaining alkali metal ions was only 3-fold with the amide carbonyls. It was also demonstrated that a single water molecule was sufficient to extract the ion from the cavity and adopt a coordination similar to the other alkali metal ions. Here, we extend the study to four water molecules, in a combined cryogenic ion trap infrared laser spectroscopic and quantum chemical computational study. Three pathways were observed for the alkali metal atoms to follow. For Li⁺, the addition of the second water leads to a distortion of the ionophore, as ion-water, water-water interactions exert their influence. For the larger ions, K⁺, Rb⁺, and Cs⁺, the ion sits comfortably above the amide carbonyls, accommodating up to three waters with no noticeable impact on the ion-ionophore structure. For Na⁺, a unique pathway is observed, where the second water weakens the ion binding to the ionophore. But it takes a third water before the ion-water and water-water interactions are able to distort the grasp of the ion by the amide carbonyl oxygens. For all five ions, the fourth water leads to a fairly uniform hydration of each ion, separating the ions from the dominant binding influence of the ionophore. Three separate paths, but one ultimate result, providing an understanding of the ion binding/releasing process with an ionophore.