Insights into the Mechanism of Thiol-Triggered COS/H2S Release from N-Dithiasuccinoyl Amines

The hydrolysis of carbonyl sulfide (COS) to form H 2 S by carbonic anhydrase has been demonstrated to be a viable strategy to deliver H 2 S in a biological system. Herein, we describe N -dithiasuccinoyl amines as thiol-triggered COS/H 2 S donors. Notably, thiol species especially GSH and homocysteine can trigger the release of both COS and H 2 S directly from several specific analogues via an unexpected mechanism. Importantly, two representative analogues Dts-1 and Dts-5 show intracellular H 2 S release, and Dts-1 imparts potent anti-inflammatory effects in LPS-challenged microglia cells. In conclusion, N -dithiasuccinoyl amine could serve as promising COS/H 2 S donors for either H 2 S biological studies or H 2 S-based therapeutics development.