Illuminating and alleviating cellular oxidative stress with an ROS-activated, H2S-donating theranostic

Abstract This paper is dedicated to Prof. Dale L. Boger on the occasion of his receipt of the 2020 Tetrahedron Prize for Creativity. Hydrogen sulfide (H2S) is an endogenous signaling molecule that has been shown to provide impressive antioxidative and cytoprotective effects. To further gauge its physiological and pathophysiological properties, small molecule donors with precise control over their H2S delivery within a biological setting are needed. Herein, we describe a novel, self-reporting H2S donor that is selectively activated by reactive oxygen species (ROS). Within our design, we append an ROS-responsive aryl boronate ester to 7-hydroxy-4-methylcoumarin via an S-alkyl thiocarbonate linkage—a key feature which provides the efficient release of both H2S (via COS hydrolysis) and a fluorescent reporter in response to elevated levels of ROS. Thus, this design was found to be a useful bifunctional tool given its rare ability to simultaneously image and neutralize hydrogen peroxide within live cells.