Thiosulfoxide (Sulfane) Sulfur: New Chemistry and New Regulatory Roles in Biology

Abstract

The understanding of sulfur bonding is undergoing change. Old theories on hypervalency of sulfur and the nature of the chalcogen-chalcogen bond are now questioned. At the same time, there is a rapidly expanding literature on the effects of sulfur in regulating biological systems. The two fields are inter-related because the new understanding of the thiosulfoxide bond helps to explain the newfound roles of sulfur in biology. This review examines the nature of thiosulfoxide (sulfane, S0) sulfur, the history of its regulatory role, its generation in biological systems, and its functions in cells. The functions include synthesis of cofactors (molybdenum cofactor, iron-sulfur clusters), sulfuration of tRNA, modulation of enzyme activities, and regulating the redox environment by several mechanisms (including the enhancement of the reductive capacity of glutathione). A brief review of the analogous form of selenium suggests that the toxicity of selenium may be due to over-reduction caused by the powerful reductive activity of glutathione perselenide.

Garlic oil polysulfides: H2S- and O2-independent prooxidants in buffer and antioxidants in cells

“…Yadav et al (63) also suggested that SSP4 is unlikely to detect low-molecular-weight persulfides in solution but instead detects thiosulfoxides [RS(ϭS)SR] and that SSP4 itself could bind to cysteine persulfides. The issue is further complicated by the possibility of tautomerization between thiosulfoxides and polysulfides (55). We have shown previously (8) and again in Fig.…”

“…In order for H 2 S to persulfidate, either it, or the protein cystine sulfur, must first undergo a two-electron oxidation to sulfane sulfur (0 formal oxidation state), or both must undergo a one-electron oxidation, which is less likely. The sulfane (thiosulfoxide) sulfur in DADS (RSSR) and DATS (RSSSR), where R denotes the allyl groups, appears to be especially important in this regard, as it can tautomerize to RS(S)R and RS(S)SR, and this sulfur is highly reactive (55).…”

“…Over 15 proteins have been shown to be regulated via sulfuration, and this number is rapidly increasing (44). However, H 2 S cannot persulfidate protein cysteines because sulfur is in its most reduced form (Ϫ2) as are the reactive protein cysteines, and their reaction is not favored (11,55). In order for H 2 S to persulfidate, either it, or the protein cystine sulfur, must first undergo a two-electron oxidation to sulfane sulfur (0 formal oxidation state), or both must undergo a one-electron oxidation, which is less likely.…”

Key bioactive reaction products of the NO/H2S interaction are S/N-hybrid species, polysulfides, and nitroxyl

“…Polysulfides were proposed to be the bioactive molecules responsible for "H 2 S signaling" and much of the physiological action of sulfide in cells (31,48,49). In addition, they are believed to act as storage or buffer molecules of H 2 S, with surprisingly high concentrations measured in murine organs/tissues (31).…”

“…HS n − (and their organic counterparts) are not resistant to reducing conditions and high concentrations of thiols, and contain a highly reactive sulfane sulfur (49,50). Polysulfides were proposed to be the bioactive molecules responsible for "H 2 S signaling" and much of the physiological action of sulfide in cells (31,48,49).…”