Many bacterial pathogens produce protein siderophores to bind and transport iron from the surrounding environment into bacterial cells. Due to their reliance on this metal scavenging mechanism for survival, synthetic analogues of siderophores serve as an attractive model for antibacterial therapeutic agents and for probing biological systems. As a chemical scaffold for photoswitches, azobenzene is among the most widely used and possesses well-characterized photochemistry with distinct absorbance spectra in the UV and visible region for its cis and trans isomers, respectively. Building upon existing work aimed at designing azobenzene photoswitches for the reversible and light driven photocontrol of biomolecules, we report the synthesis and photophysical characterization of azobenzene derivatives of rhizoferrin as potential photoswitchable metal chelators. To evaluate the efficacy of ligand metal binding, as reflected by slower cis to trans thermal relaxation rates, we conducted kinetic studies using UV/Vis spectroscopy of our synthetic siderophore in the presence of various metals. Additionally, we explored the effect of modifying the electronics and length of the chelating “arms” to optimize metal coordination in the active cis state, and to attenuate isomerization back to the inactive and thermodynamically favored trans state. Our efforts to couple the inherent photochromism of azobenzene with the metal-binding ability of siderophores provides novel insight into the structure-activity relationship of a tunable platform for photoswitchable antibacterial design.

Photoswitchable metal chelators: Azobenzene driven synthetic siderohphores as a model for antibacterial design

ACS Spring 2022

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