Oxidation of Disulfides to Thiolsulfinates with Hydrogen Peroxide and a Cyclic Seleninate Ester Catalyst

• Published in: Molecules (Basel, Switzerland) Vol. 20; no. 6; pp. 10748 - 10762
• Main Authors: McNeil, Nicole M R, McDonnell, Ciara, Hambrook, Miranda, Back, Thomas G
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 11-06-2015; MDPI
• Subjects: Acids; Antioxidants - chemistry; Antioxidants - metabolism; Catalysts; Catalytic oxidation; cyclic seleninate esters; Cystine - analogs & derivatives; Cystine - chemistry; Dimethyl; Disulfides; Disulfides - chemistry; Disulfides - metabolism; Esters; Esters - chemistry; Esters - metabolism; Glutathione Peroxidase - chemistry; Glutathione Peroxidase - metabolism; glutathione peroxide mimetics; Hydrogen peroxide; Hydrogen Peroxide - chemistry; Molecular Mimicry; Organoselenium Compounds - metabolism; organoselenium redox catalysts; Oxidation; Oxidation-Reduction; Oxidative stress; Peptides; Spectators; Sulfhydryl Compounds - chemistry; thiolsulfinates; cyclic seleninate esters; organoselenium redox catalysts; disulfides; thiolsulfinates; glutathione peroxide mimetics
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules200610748

Cyclic seleninate esters function as mimetics of the antioxidant selenoenzyme glutathione peroxidase. They catalyze the reduction of harmful peroxides with thiols, which are converted to disulfides in the process. The possibility that the seleninate esters could also catalyze the further oxidation of disulfides to thiolsulfinates and other overoxidation products under these conditions was investigated. This has ramifications in potential medicinal applications of seleninate esters because of the possibility of catalyzing the unwanted oxidation of disulfide-containing spectator peptides and proteins. A variety of aryl and alkyl disulfides underwent facile oxidation with hydrogen peroxide in the presence of catalytic benzo-1,2-oxaselenolane Se-oxide affording the corresponding thiolsulfinates as the principal products. Unsymmetrical disulfides typically afforded mixtures of regioisomers. Lipoic acid and N,N'-dibenzoylcystine dimethyl ester were oxidized readily under similar conditions. Although isolated yields of the product thiolsulfinates were generally modest, these experiments demonstrate that the method nevertheless has preparative value because of its mild conditions. The results also confirm the possibility that cyclic seleninate esters could catalyze the further undesired oxidation of disulfides in vivo.