Cysteine-activated hydrogen sulfide (H₂S) delivery through caged carbonyl sulfide (COS) donor motifs

Abstract

Hydrogen sulfide (H2S) is an important biomolecule, and controllable H2S donors are needed to investigate H2S biological functions. Here we utilize cysteine-mediated addition/cyclization chemistry to unmask an acrylate-functionalized thiocarbamate and release carbonyl sulfide (COS), which is quickly converted to H2S by carbonic anhydrase (CA).

Fluorogenic hydrogen sulfide (H2S) donors based on sulfenyl thiocarbonates enable H2S tracking and quantification

“…1a). 34 Expanding on this initial report, we, as well as others, have applied the similar caged-COS systems to include a series of triggerable COS-based H 2 S donors which can be activated by different mechanisms, such as reactive oxygen species (ROS),35–37 esterase,38,39 cellular nucleophiles,40 click chemistry,41 light,42–44 and Cys,45 to release H 2 S under various conditions 45,46…”

Self-amplified depolymerization of oligo(thiourethanes) for the release of COS/H2S

“…The released COS was then rapidly hydrolyzed to H 2 S via the action of the ubiquitous enzyme carbonic anhydrase (CA). Since this seminal work on small molecule thiocarbamates as dual COS/H 2 S donors, Pluth and coworkers have demonstrated the ability to trigger COS/H 2 S release in the presence of other stimuli including hydrogen peroxide, 28 cysteine, 29 light, 30 and others. 29,31 We envisioned that leveraging benzyl thiocarbamates as the repeat unit of a depolymerizable polymer would provide an exciting opportunity for a platform from which endogenous H 2 S production may be amplified, creating a self-amplified depolymerizable polymer (SADP) (Scheme 1C).…”

Thionoesters: A Native Chemical Ligation-Inspired Approach to Cysteine-Triggered H2S Donors

“…To the best of our knowledge, the only reported cysteine-selective H 2 S donor utilizes the established reactivity of acrylate Michael acceptors toward cysteine, 26 to subsequently trigger the generation of COS, which is quickly converted to H 2 S by carbonic anhydrase. 27…”