Controlling Antibacterial Activity Exclusively with Visible Light: Introducing a Tetra‐ortho‐Chloro‐Azobenzene Amino Acid

The introduction of a novel tetra‐ortho‐chloroazobenzene amino acid (CEBA) has enabled photoswitching of the antimicrobial activity of tyrocidine A analogues by using exclusively visible light, granting spatiotemporal control under benign conditions. Compounds bearing this photoswitchable amino acid become active upon irradiation with red light, but quickly turn‐off upon exposure to other visible light wavelengths. Critically, sunlight quickly triggers isomerisation of the red light‐activated compounds into their original trans form, offering an ideal platform for self‐deactivation upon release into the environment. Linear analogues of tyrocidine A were found to provide the best photocontrol of their antimicrobial activity, leading to compounds active against Acinetobacter baumannii upon isomerisation. Exploration of their N‐ and C‐termini has provided insights into key elements of their structure and has allowed obtaining new antimicrobials displaying excellent strain selectivity and photocontrol.