Stacked Sandwich-type Beauvericin Complex Revealed by Cryogenic Ion Mobility and Infrared Spectroscopy: Insight into...

Understanding the molecular mechanisms underlying ion transport selectivity is a central issue in supramolecular chemistry and biochemistry. Beauvericin (Bv), a naturally occurring cyclic hexadepsipeptide, selectively transports physiologically relevant Ca²⁺ across cell membranes. Although the 2:1 (Bv-M-Bv) complex has been proposed as a key driver of ion transport, its detailed conformations and contribution to selectivity remain unclear. Here, we systematically investigated the Bv-M-Bv complexes with alkaline-earth and alkali metal ions using cryogenic ion mobility and cryogenic IR spectroscopy. Comparison of collision cross sections, IR spectra, and quantum chemical calculations enabled strongly supported assignments to the stacked, tilted, and shifted conformers, whose relative abundances depend strongly on the size and charge of the encapsulated metal ions. Notably, the Bv-Ca²⁺-Bv complex preferentially adopts the most compact stacked conformation, which may enhance diffusion across cell membranes. These findings provide molecular-level insights into ion transport selectivity governed by structural flexibility.