Sense and release: A cysteine-responsive, flavonol-based photoCORM

Biothiols, namely glutathione, homocysteine, and cysteine (Cys), are considered non-enzymatic redox indicators and perturbation of their levels is related to various diseases. Cellular cysteine levels are of particular current interest due to its participation in reversible redox reactions and cellular detoxification. Cellular redox homeostasis, including relative thiol concentrations, is regulated by maintaining a balance between reactive oxygen species (ROS) and their elimination. Notably, changes in cellular carbon monoxide levels are known to influence ROS generation. In this context, it is desirable to have a CO-releasing molecule that communicates the redox state of the cell prior to delivering CO. To meet this need, our laboratory has developed a Cys-sensitive CO-releasing molecule based on a flavonol motif. This molecule is selective for cysteine over other biothiols, exhibits nanomolar sensitivity, and is trackable in real time prior to CO release. This is the first example of a photoCORM that provides preliminary insight into the biological environment and then can be triggered for CO release