Using resonance synchronous spectroscopy to characterize the reactivity and electrophilicity of biologically relevant sulfane sulfur

Rui Zhao,Zhigang Chen,Huanjie Li,Xin Hu,Huaiwei Liu,Mingxue Ran,Luying Xun,Yongzhen Xia,Jihua Liu,Qingda Wang,Ming Xian

doi:10.1016/j.redox.2019.101179

Rui Zhao, Zhigang Chen

Open Access

https://doi.org/10.1016/j.redox.2019.101179

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Abstract

Sulfane sulfur is common inside cells, playing both regulatory and antioxidant roles. However, there are unresolved issues about its chemistry and biochemistry. We report the discovery that reactive sulfane sulfur such as polysulfides and persulfides could be detected by using resonance synchronous spectroscopy (RS2). With RS2, we showed that inorganic polysulfides at low concentrations were unstable with a half-life about 1 min under physiological conditions due to reacting with glutathione. The protonated form of glutathione persulfide (GSSH) was electrophilic and had RS2 signal. GSS− was nucleophilic, prone to oxidation, but had no RS2 signal. Using this phenomenon, pKa of GSSH was determined as 6.9. GSSH/GSS− was 50-fold more reactive than H2S/HS− towards H2O2 at pH 7.4, supporting reactive sulfane sulfur species like GSSH/GSS− may act as antioxidants inside cells. Further, protein persulfides were shown to be in two forms: at pH 7.4 the deprotonated form (R-SS-) without RS2 signal was not reactive toward sulfite, and the protonated form (R-SSH) in the active site of a rhodanese had RS2 signal and readily reacted with sulfite to produce thiosulfate. These data suggest that RS2 of sulfane sulfur is likely associated with its electrophilicity. Sulfane sulfur showed species-specific RS2 spectra and intensities at physiological pH, which may reveal the relative abundance of a reactive sulfane sulfur species inside cells.

Highlights

Hydrogen sulfide (H2S) is a new gasotransmitter that serves many important regulatory roles in biological systems [1]
Reactive sulfane sulfur is different from thiols, as it often possesses both nucleophilic and electrophilic characteristics while thiols mainly function as nucleophiles [8]
Distilled water and 50 mM Tris-HCl had low RS2, and we used the TrisHCl or HEPES buffer for most analyses (Fig. 1A). To test whether it is a common property of sulfur-containing compounds, we totally analyzed 14 sulfur-containing chemicals that were sorted into 7 clusters (Table 1)

Summary

Introduction

Hydrogen sulfide (H2S) is a new gasotransmitter that serves many important regulatory roles in biological systems [1]. Reactive sulfane sulfur includes organic persulfides (R-SSH), organic polysulfides (R-SSnH or R-SSnR, n ≥ 2), and inorganic hydrogen polysulfides (H2Sn, n ≥ 2) [7]. Reactive sulfane sulfur is different from thiols, as it often possesses both nucleophilic and electrophilic characteristics while thiols mainly function as nucleophiles [8]. GSSH is a key form of reactive sulfane sulfur in the sulfide oxidation pathway of heterotrophic bacteria and human mitochondria [14,15]. Reactive sulfane sulfur can modify cysteine residues in a large number of proteins by S-persulfidation (R-SSH), which can alter enzyme activity and influence biological processes via signaling [13,16]. Previous reports have revealed the significance of reactive sulfane sulfur in biological processes. A better understanding of the chemical and biochemical properties of biologically relevant reactive sulfane sulfur will help to advance the field [19,20]

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