Selenium-Based Catalytic Scavengers for Concurrent Scavenging of H2 S and Reactive Oxygen Species.

Hydrogen sulfide (H2 S) is an endogenous gasotransmitter that plays important roles in redox signaling. H2 S overproduction has been linked to a variety of disease states and therefore, H2 S-depleting agents, such as scavengers, are needed to understand the significance of H2 S-based therapy. It is known that elevated H2 S can induce oxidative stress with elevated reactive oxygen species (ROS) formation, such as in H2 S acute intoxication. We explored the possibility of developing catalytic scavengers to simultaneously remove H2 S and ROS. Herein, we studied a series of selenium-based molecules as catalytic H2 S/H2 O2 scavengers. Inspired by the high reactivity of selenoxide compounds towards H2 S, 14 diselenide/monoselenide compounds were tested. Several promising candidates such as S6 were identified. Their activities in buffers, as well as in plasma- and cell lysate-containing solutions were evaluated. We also studied the reaction mechanism of this scavenging process. Finally, the combination of the diselenide catalyst and photosensitizers was used to achieve light-induced H2 S removal. These Se-based scavengers can be useful tools for understanding H2 S/ROS regulations.

Thioglucose-derived tetrasulfide, a unique polysulfide model compound.

Polysulfides have received increased interest in redox biology due to their role as the precursors of H2S and persulfides. However, the compounds that are suitable for biological investigations are limited to cysteine- and glutathione-derived polysulfides. In this work, we report the preparation and evaluation of a novel polysulfide derived from thioglucose, which represents the first carbohydrate-based polysulfide. This compound, thioglucose tetrasulfide (TGS4), showed excellent stability and water solubility. H2S and persulfide production from TGS4, as well as its associated antioxidative property were also demonstrated. Additionally, TGS4 was demonstrated to significantly induce cellular sulfane sulfur level increase, in particular for the formation of hydropersulfides/trisulfides. These results suggest that TGS4 is a useful tool for polysulfide research.

Geminal-dithiol-based precursors for reactive sulfur species.

Caged gem-dithiols have been developed as the donors of reactive sulfur species (RSS), but the chemistry of free gem-dithiols as RSS donors has not been well understood. Herein, we report the study of a free gem-dithiol, 1,3-diphenylpropane-2,2-dithiol, as the precursor for several RSS. It releases H2S under physiological conditions and can be converted to a mono-S-nitrosothiol, which serves as a NO donor. Furthermore, it can be converted to 3,3-dibenzyldithiirane, which is an active sulfur transfer reagent and can induce S-persulfidation.

2H-Thiopyran-2-thione sulfine, a compound for converting H2S to HSOH/H2S2 and increasing intracellular sulfane sulfur levels.

Reactive sulfane sulfur species such as persulfides (RSSH) and H2S2 are important redox regulators and closely linked to H2S signaling. However, the study of these species is still challenging due to their instability, high reactivity, and the lack of suitable donors to produce them. Herein we report a unique compound, 2H-thiopyran-2-thione sulfine (TTS), which can specifically convert H2S to HSOH, and then to H2S2 in the presence of excess H2S. Meanwhile, the reaction product 2H-thiopyran-2-thione (TT) can be oxidized to reform TTS by biological oxidants. The reaction mechanism of TTS is studied experimentally and computationally. TTS can be conjugated to proteins to achieve specific delivery, and the combination of TTS and H2S leads to highly efficient protein persulfidation. When TTS is applied in conjunction with established H2S donors, the corresponding donors of H2S2 (or its equivalents) are obtained. Cell-based studies reveal that TTS can effectively increase intracellular sulfane sulfur levels and compensate for certain aspects of sulfide:quinone oxidoreductase (SQR) deficiency. These properties make TTS a conceptually new strategy for the design of donors of reactive sulfane sulfur species.