76 - Chemical Tools for Delivery of COS and H2S

Abstract

Hydrogen sulfide (H2S) and related reactive sulfur species are now recognized to play important and expanded roles in biology, health, and disease. Aligned with this increased interest, chemical tools that enable H2S delivery have emerged as important research tools with high pharmacological potential. In our efforts to expand the available toolbox of compounds that enable H2S-delivery, we have recently demonstrated H2S release from synthetic polysulfides as well as caged thiocarbamate motifs. The thiocarbamate-based H2S donors function through the initial release of carbonyl sulfide (COS), which is quickly converted to H2S by carbonic anhydrase (CA), which is expressed widely in mammalian systems. One added benefit of such systems is that they can be tuned to release COS/H2S in response to specific biological or biorthogonal stimuli, thus providing a broad platform for tuning the donor motifs for specific applications. This presentation will focus on recent work from our lab aimed at (1) diversifying available COS/H2S donor core motifs and (2) preparing and applying new COS donors activated by specific stimuli, including biologically-relevant small molecules, bio-orthogonal triggers, and enzymatic reactions. In addition, we will also provide early insights into mitochondrial bioenergetics measurements that suggest that COS may exert different activities than H2S in certain systems, thus highlighting the potential biological roles of this under-investigated small molecule.