Compact Conformation of Ba²⁺-Beauvericin Complex by Triple Cation-π Interactions: Insight into Ion Transport Mechanism from Gas-Phase Structures

Beauvericin (BEA), a natural cyclic hexadepsipeptide ionophore, can selectively transport metal ions through lipid bilayers. Although BEA can transport Ca²⁺ and Ba²⁺, previous studies have not yet revealed its ion-selective transport mechanism. In the present study, we identified a novel conformation of 1:1 BEA complexes selectively stabilized by triple cation-π interactions with Ba²⁺ among alkaline-earth and alkali metal ions, using electrospray ionization-ion mobility-mass spectrometry (ESI-IM-MS). The calculated IR spectrum of this conformation was well reproduced with the experimental IR photodissociation spectrum of the 1:1 BEA complex with Ba²⁺, which was not assigned previously. This conformation can maximize membrane permeability across lipid bilayers since its size (collision cross section) and polarity (solvent accessible 3D polar surface area) are very small and apolar, respectively. The gas phase structures provide insight into BEA's structure-function relationship, in which the formation of a compact and apolar conformation facilitates ion-selective transport.