Intermolecular Association Model of Antifungal Polyene Macrolide via Concerted =C–H···O Interactions: X-ray Crystal Structure Analysis and Ab Initio Molecular-Orbital Calculations of Chainin

The absolute configuration of chainin (1), a polyene macrolide antibiotic, was determined by X-ray crystal analyses, and the conformational stability of planar 28-membered ring was confirmed by an ab initio quantum chemical calculation. The most prominent feature observed in the crystal structure was the concerted =C–H···O interactions formed between four conjugated olefinic CH groups and five hydroxyl oxygen atoms of neighboring molecules. The character of the interaction was investigated by IR measurements and quantum chemical calculations, leading to the conclusion that these concerted interactions are powerful enough to form defined intermolecular association of polyene macrolide. Characteristically, this intermolecular association mode allows the proposal of a barrel-stave assembly, comprising eight parallel or antiparallel pairs of 1 via =C–H···O interactions, which serves as a possible ion-permeable membrane channel structure of polyene macrolide, which may be responsible for the antifungal activity in cell membranes.