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.

Organelle-Targeted Fluorescent Probes for Sulfane Sulfur Species.

Sulfane sulfurs, which include hydropersulfides (RSSH), hydrogen polysulfides (H2Sn, n > 1), and polysulfides (RSnR, n > 2), play important roles in cellular redox biology and are closely linked to hydrogen sulfide (H2S) signaling. While most studies on sulfane sulfur detection have focused on sulfane sulfurs in the whole cell, increasing the recognition of the effects of reactive sulfur species on the functions of various subcellular organelles has emerged. This has driven a need for organelle-targeted detection methods. However, the detection of sulfane sulfurs, particularly of RSSH and H2Sn, in biological systems is still a challenge due to their low endogenous concentrations and instabilities. In this review, we summarize the development and design of organelle-targeted fluorescent sulfane sulfur probes, examine their organelle-targeting strategies and choices of fluorophores (e.g., ratiometric, near-infrared, etc.), and discuss their mechanisms and ability to detect endogenous and exogenous sulfane sulfur species. We also present the advantages and limitations of the probes and propose directions for future work on this topic.

Benzothiazole-Derived Sulfones and Sulfoxides as Reactive Templates for Biothiols and Sulfane Sulfurs.

In this work we studied the reactions of benzothiazole sulfones and sulfoxides toward reactive sulfur species. The reaction of thiols with benzothiazole sulfones produces sulfinic acids (RSO2H), which can further react with sulfane sulfurs to form thiosulfonic acids (RSO2SH). This was used to design fluorescent sensors for hydrogen polysulfides. The reaction of thiols with benzothiazole sulfoxides produces sulfenic acids (RSOH), which can undergo fast intramolecular cyclization and be used to design thiol-triggered fluorescent sensors.

Methods for Suppressing Hydrogen Sulfide in Biological Systems.

Significance: Hydrogen sulfide (H2S) plays critical roles in redox biology, and its regulatory effects are tightly controlled by its cellular location and concentration. The imbalance of H2S is believed to contribute to some pathological processes. Recent Advances: Downregulation of H2S requires chemical tools such as inhibitors of H2S-producing enzymes and H2S scavengers. Recent efforts have discovered some promising inhibitors and scavengers. These advances pave the road toward better understanding of the functions of H2S. Critical Issues: Precise H2S downregulation is challenging. The potency and specificity of current inhibitors are still far from ideal. H2S-producing enzymes are involved in complex sulfur metabolic pathways and ubiquitously present in biological matrices. The inhibition of these enzymes can cause unwanted side effects. H2S scavengers allow targeted H2S clearance, but their options are still limited. In addition, the scavenging process often results in biologically active by-products. Future Directions: Further development of potent and specific inhibitors for H2S-producing enzymes is needed. Scavengers that can rapidly and selectively remove H2S while generating biocompatible by-products are needed. Potential therapeutic applications of scavengers and inhibitors are worth exploring. Antioxid. Redox Signal. 36, 294-308.