Hydrogen Sulfide Donors Activated by Reactive Oxygen Species

Angew Chem Int Ed Engl. 2016 Nov 14;55(47):14638-14642. doi: 10.1002/anie.201608052. Epub 2016 Oct 24.


Hydrogen sulfide (H2 S) exhibits promising protective effects in many (patho)physiological processes, as evidenced by recent reports using synthetic H2 S donors in different biological models. Herein, we report the design and evaluation of compounds denoted PeroxyTCM, which are the first class of reactive oxygen species (ROS)-triggered H2 S donors. These donors are engineered to release carbonyl sulfide (COS) upon activation, which is quickly hydrolyzed to H2 S by the ubiquitous enzyme carbonic anhydrase (CA). The donors are stable in aqueous solution and do not release H2 S until triggered by ROS, such as hydrogen peroxide (H2 O2 ), superoxide (O2- ), and peroxynitrite (ONOO- ). We demonstrate ROS-triggered H2 S donation in live cells and also demonstrate that PeroxyTCM-1 provides protection against H2 O2 -induced oxidative damage, suggesting potential future applications of PeroxyTCM and similar scaffolds in H2 S-related therapies.

Keywords: carbonyl sulfide; hydrogen sulfide; oxidative stress; reactive oxygen species; thiocarbamate.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Carbonic Anhydrases / chemistry
  • Carbonic Anhydrases / metabolism
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • HeLa Cells
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Hydrogen Sulfide / chemistry
  • Hydrogen Sulfide / metabolism*
  • Mice
  • Molecular Structure
  • RAW 264.7 Cells
  • Reactive Oxygen Species / metabolism*
  • Structure-Activity Relationship


  • Reactive Oxygen Species
  • Hydrogen Peroxide
  • Carbonic Anhydrases
  • Hydrogen Sulfide