H2S signals via protein persulfidation. To be regulatory the modification will have to be reversible. Using a new method for persulfide detection, we discover this missing link and show that thioredoxin system acts as depersulfidase in vivo.

The steric bulk of the phosphane ligand determines the mechanism of the ArX addition to zero‐valent [PdL2] complexes. This effect has been studied by variation of ligands (catalyst: [Pd(PCxntBu3−n)2]; n=0–3, Cx=cyclohexyl) in Pd couplings of unsaturated electrophiles, and different reaction pathways (A=associative, B=dissociative) identified, depending on the size of the ligand.

The proposal of the post-translational modification "S-sulfhydration" as a major pathway for H2 S-induced signaling has recently shed light on persulfides. However, the study of these species is hampered by their instability under biologically relevant conditions; this requires generating them in situ immediately prior to use. The current methods to prepare persulfides in aqueous solution suffer from several drawbacks. In particular, their formation requires (or generates) hydrogen sulfide, thus resulting in difficulties in distinguishing polysulfide reactivity from that of H2 S. Here we report the H2 S-free formation, characterization, and some biologically relevant reactions of a water-soluble persulfide analogue of the nitrosothiol SNAP, a widely used nitric oxide donor.

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Accumulating evidence suggests that abnormal levels of homocysteine are associated with vascular dysfunctions, cancer cell proliferation and various neurodegenerative diseases. With respect to the latter, a perturbation of transition metal homeostasis and an inhibition of catalase bioactivity have been reported. Herein, we report on some of the molecular bases for the cellular toxicity of homocysteine and demonstrate that it induces the formation of sulfcatalase, an irreversible inactive state of the enzyme, without the intervention of hydrogen sulfide. Initially, homocysteine reacts with native catalase and/or redox-active transition metal ions to generate thiyl radicals that mediate compound II formation, a temporarily inactive state of the enzyme. Then, the ferryl centre of compound II intervenes into the unprecedented S-oxygenation of homocysteine to engender the corresponding sulfenic acid species that further participates into the prosthetic heme modification through the formation of an unusual Fe(II) sulfonium. In addition, our ex cellulo studies performed on cancer cells, models of neurodegenerative diseases and ulcerative colitis suggest the likelihood of this scenario in a subset of cancer cells, as well as in a cellular model of Parkinson's disease. Our findings expand the repertoire of heme modifications promoted by biological compounds and point out another deleterious trait of disturbed homocysteine levels that could participate in the aetiology of these diseases.

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Generous donors: The dithioperoxyanhydrides (CH3 COS)2 , (PhCOS)2 , CH3 COSSCO2 Me and PhCOSSCO2 Me act as thiol-activated hydrogen sulfide donors in aqueous buffer solution. The most efficient donor (CH3 COS)2 can induce a biological response in cells, and advantageously replace hydrogen sulfide in ex vivo vascular studies.

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