Frontispiece: Use of Dithiasuccinoyl‐Caged Amines Enables COS/H₂S Release Lacking Electrophilic Byproducts

Abstract

The thiol‐mediated reduction of dithiasuccinoyl groups was harnessed to develop a method for controlled carbonyl sulfide (COS) generation under buffered aqueous conditions. This reactivity generates two equivalents of COS and does not result in formation of electrophilic byproducts such as (imino)quinone methides. The rate of COS generation can be tuned as function of amine identity, and theoretical investigations provide key insights into COS release from thiocarbamate intermediates. For more information, see the Full Paper by M. D. Pluth and co‐workers on page 5374 ff.

Thiol-Activated 1,2,4-Thiadiazolidin-3,5-diones Release Hydrogen Sulfide through a Carbonyl-Sulfide-Dependent Pathway

“…A now common approach to developing H 2 S donors is to design molecules that can be engineered to release carbonyl sulfide (COS), which can be rapidly converted to H 2 S by the enzyme carbonic anhydrase (CA) . CA is a ubiquitous enzyme that maintains endogenous pH but can also readily convert COS to H 2 S, which provides a simple approach for delivering H 2 S through the intermediate release of COS. Our group, as well as others, has developed a palette of COS-releasing H 2 S donors, including self-immolative thiocarbamates, − N -thiocarboxyanhydrides, − sulfenyl thiocarbonates, dithiasuccinoyl compounds, , cyclic sulfenyl thiocarbamates, and N -alkyl perthiocarbamates, as well as other approaches (Figure a). These donors all have similar COS-producing moieties and proceed through common intermediates prior to COS/H 2 S release.…”