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

Cysteine is the most acidic of the three common redox active amino acids with p<i>K</i>_a = 8.2 for the thiol compared to p<i>K</i>_a = 10.1 for the phenol in tyrosine and p<i>K</i>_a ≈ 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 <i>L</i>-cysteine and <i>N</i>-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 (HPO₄^2–) as proton acceptor bases in concerted electron–proton transfer (EPT) pathways in the oxidation of <i>L</i>-cysteine and <i>N</i>-acetyl-cysteine with good agreement between rate constant data obtained by electrochemical and stopped-flow methods