Photoswitchable Antimicrobial Metallohelices

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.