Photoswitchable Antimicrobial Metallohelices

Abstract

Chiral subcomponent self-assembly is used to access optically pure, metallo-helical species based on Zn and Fe(II) and incorporating three trans-azobenzene units. UV-visible, circular dichroism and NMR spectroscopies, alongside X-ray crystallographic and DFT computational studies are used to unambiguously characterize a highly reversible stepwise photochemical transformation to an all-cis state in which structural integrity and optical purity have been retained. While the all-trans state of the water-soluble enantiomers exhibited low or moderate activity against Gram-positive strains, irradiation at 365 nm led to up to eight-fold reduction in MIC. Electron microscopy and a cell permeability assay indicate a membrane disruption mechanism; the higher activity of the photochemically-generated all-cis state is consistent with its more compact supramolecular fold.