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

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 provide a useful bifunctional tool given its rare ability to simultaneously image and neutralize hydrogen peroxide within live cells. (C) 2021 Elsevier Ltd. All rights reserved.

Automated summary

This paper describes a novel, self-reporting H2S donor selectively activated by ROS, which can efficiently release H2S and a fluorescent reporter in response to elevated ROS levels. The design provides a useful bifunctional tool for imaging and neutralizing hydrogen peroxide within live cells.