Reaction of Hydrogen Sulfide with Disulfide and Sulfenic Acid to Form the Strongly Nucleophilic Persulfide.
Hydrogen sulfide (H2S) is increasingly recognized to modulate physiological processes in mammals through mechanisms that are currently under scrutiny. H2S is not able to react with reduced thiols (RSH). However, H2S, more precisely HS(-), is able to react with oxidized thiol derivatives. We performed a systematic study of the reactivity of HS(-) toward symmetric low molecular weight disulfides (RSSR) and mixed albumin (HSA) disulfides. Correlations with thiol acidity and computational modeling showed that the reaction occurs through a concerted mechanism. Comparison with analogous reactions of thiolates indicated that the intrinsic reactivity of HS(-) is 1 order of magnitude lower than that of thiolates. In addition, H2S is able to react with sulfenic acids (RSOH). The rate constant of the reaction of H2S with the sulfenic acid formed in HSA was determined. Both reactions of H2S with disulfides and sulfenic acids yield persulfides (RSSH), recently identified post-translational modifications. The formation of this derivative in HSA was determined, and the rate constants of its reactions with a reporter disulfide and with peroxynitrite revealed that persulfides are better nucleophiles than thiols, which is consistent with the α effect. Experiments with cells in culture showed that treatment with hydrogen peroxide enhanced the formation of persulfides. Biological implications are discussed. Our results give light on the mechanisms of persulfide formation and provide quantitative evidence for the high nucleophilicity of these novel derivatives, setting the stage for understanding the contribution of the reactions of H2S with oxidized thiol derivatives to H2S effector processes.
Laboratorios de Enzimología, Universidad de la República, 11400 Montevideo, Uruguay; Center for Free Radical and Biomedical Research, Universidad de la República, 11400 Montevideo, Uruguay.
Ernesto
E
Cuevasanta
Department of Chemistry and Pharmacy, Division of Bioinorganic Chemistry, Friedrich-Alexander University of Erlangen-Nuremberg, 91058 Erlangen, Germany.
Mike
M
Lange
Química Teórica y Computacional, Universidad de la República, 11400 Montevideo, Uruguay.
Jenner
J
Bonanata
Química Teórica y Computacional, Universidad de la República, 11400 Montevideo, Uruguay.
E Laura
EL
Coitiño
Center for Free Radical and Biomedical Research, Universidad de la República, 11400 Montevideo, Uruguay; Fisicoquímica Biológica, Facultad de Ciencias, Universidad de la República, 11400 Montevideo, Uruguay.
Gerardo
G
Ferrer-Sueta
Department of Chemistry and Pharmacy, Division of Bioinorganic Chemistry, Friedrich-Alexander University of Erlangen-Nuremberg, 91058 Erlangen, Germany. Electronic address: milos.filipovic@fau.de.
Milos R
MR
Filipovic
Laboratorios de Enzimología, Universidad de la República, 11400 Montevideo, Uruguay; Center for Free Radical and Biomedical Research, Universidad de la República, 11400 Montevideo, Uruguay. Electronic address: beatriz.alvarez@fcien.edu.uy.
Beatriz
B
Alvarez
D002460:Cell Line; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006862:Hydrogen Sulfide / Q000737:chemistry / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008954:Models, Biological; D008956:Models, Chemical; D008970:Molecular Weight; D010084:Oxidation-Reduction; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism; D013434:Sulfenic Acids / Q000737:chemistry / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000378:metabolism; D013440:Sulfides / Q000737:chemistry / Q000378:metabolism*
D004220:Disulfides; D012709:Serum Albumin; D013434:Sulfenic Acids; D013438:Sulfhydryl Compounds; D013440:Sulfides; C051552:persulfides; D006862:Hydrogen Sulfide
disulfide; hydrodisulfide; hydrogen sulfide; kinetics; persulfide; sulfenic acid; sulfhydryl; thiol