Intramolecular Thiol- and Selenol-Assisted Delivery of Hydrogen Sulfide.

Arylthioamides have been frequently employed to assess the chemical biology and pharmacology of hydrogen sulfide (H2 S). From this class of donors, however, extremely low H2 S releasing efficiencies have been reported and proper mechanistic studies have been omitted. Consequently, millimolar concentrations of arylthioamides are required to liberate just trace amounts of H2 S, and via an unidentified mechanistic pathway, which obfuscates the interpretation of any biological activity that stems from their use. Herein, we report that H2 S release from this valuable class of donors can be markedly enhanced through intramolecular nucleophilic assistance. Specifically, we demonstrate that both disulfide- and diselenide-linked thioamides are responsive to biologically relevant concentrations of glutathione and release two molar equivalents of H2 S via an intramolecular cyclization that significantly augments their rate and efficiency of sulfide delivery in both buffer and live human cells.

Highly selective staining and quantification of intracellular lipid droplets with a compact push-pull fluorophore based on benzothiadiazole.

A robust lipophilic dye, based on the structures of the benzothiadiazole heterocycle, was shown to be a potent fluorescent stain for the selective imaging of lipid droplets (LDs) within both live and fixed human cells. Its small molecular framework, large Stokes shift, and vastly improved photostability over that of the current status quo, Nile Red, highlight its tremendous potential as a versatile chemical tool for facilitating LD imaging and research.

An Innovative Hydrogen Peroxide-Sensing Scaffold and Insight Towards its Potential as an ROS-Activated Persulfide Donor.

Reactive sulfur species, such as hydrogen sulfide, persulfides, and polysulfides, have recently emerged as key signaling molecules and important physiological mediators within mammalian systems. To better assess the therapeutic potential of their exogenous administration, we report on the development of a unique hydrogen peroxide (H2 O2 )-sensing motif and its capacity for providing cellular protection against oxidative stress while serving as a reactive oxygen species (ROS)-activated persulfide donor. With the strategic implementation of a gem-dimethyl group to promote both stability and cyclization, we found the initial rate of payload release from this newly derived scaffold to be directly proportional to the concentration of H2 O2 and to proceed via an unprecedented pathway that avoids the production of electrophilic byproducts, a severe limitation that has plagued the physiological application of previous designs.

Selenosulfides Tethered to gem-Dimethyl Esters: A Robust and Highly Versatile Framework for H2 S Probe Development.

Selenosulfides coupled to gem-dimethyl esters provide an exceptional platform for H2 S probe development. With the sulfur half being nonessential to its high reactivity and selectivity towards H2 S, we highlight the unique flexibility of our design by improving its biocompatibility and tissue specificity through structural modifications of its sulfide moiety.