Concerted Electron–Proton Transfer (EPT) in the Oxidation of Cysteine

Abstract

Cysteine is the most acidic of the three common redox active amino acids with pKa = 8.2 for the thiol compared to pKa = 10.1 for the phenol in tyrosine and pKa ≈ 16 for the indole proton in tryptophan. Stopped-flow and electrochemical measurements have been used to explore the role of proton-coupled electron transfer (PCET) and concerted electron–proton transfer (EPT) in the oxidations of L-cysteine and N-acetyl-cysteine by the polypyridyl oxidants M(bpy)33+ (M = Fe, Ru, Os) and Ru(dmb)33+ (bpy is 2,2′-bipyridine, and dmb is 4,4′-dimethyl-2,2′-bipyridine). Oxidation is rate limited by initial 1e– electron transfer to M(bpy)33+, with added proton acceptor bases, by multiple pathways whose relative importance depends on reaction conditions. The results of these studies document important roles for acetate (AcO–) and phosphate (HPO42–) as proton acceptor bases in concerted electron–proton transfer (EPT) pathways in the oxidation of L-cysteine and N-acetyl-cysteine with good agreement between rate constant data obtained by electrochemical and stopped-flow methods.