persulfides

Persulfides are chemical species characterized by a sulfur-sulfur bond adjacent to a thiol group, commonly represented as RSSH where R is an organic substituent. The simplest persulfide motif is the -S–S–H unit, giving organic persulfides such as cysteine persulfide (Cys–SSH) and glutathione persulfide (GSSH). Persulfides include both organic derivatives and simple hydropersulfide forms found in biology.

In chemistry and biology, persulfides can arise when thiols react with sulfur-containing donors or when hydrogen sulfide engages in redox transformations. In living systems, enzymes such as cystathionine gamma-lyase, cystathionine beta-synthase, and 3-mercaptopyruvate sulfurtransferase contribute to persulfide formation, producing low-molecular-weight species and modifying protein thiols to form persulfide groups. Persulfides are also formed non-enzymatically under oxidative or sulfane-sulfur–rich conditions.

Chemically, persulfides are more acidic than their thiol precursors and are relatively good nucleophiles and reductants due to the extra sulfur atom. The S–S bond in RSSH enables transfer of sulfane sulfur to other molecules and participation in redox chemistry. They can be oxidized to thiosulfonates or other higher sulfur-oxidized species, and they readily participate in S-sulfhydration of protein cysteine residues, a modification implicated in redox signaling.

Biological roles of persulfides include participation in redox signaling, cytoprotection, and modulation of cellular responses to oxidative stress. They are investigated for their potential antioxidant effects and involvement in disease-related pathways. Analytical detection and quantification typically rely on mass spectrometry and chemical tagging strategies that stabilize and identify the extra sulfur moiety.