Kinetics of one-electron oxidation of thiols and hydrogen abstraction by thiyl radicals from α-amino C-H bonds

Article abstract of DOI:10.1021/ja00105a048

One-electron oxidation of cysteine, homocysteine, and glutathione by azide radical in alkaline solution (pH 10.5), where both the amino and the SH groups are deprotonated, has been investigated by pulse radiolysis. Reducing α-aminoalkyl radicals (^?CR), which are formed via intramolecular rearrangement of thiyl radicals, were detected using methylviologen as oxidant in the kinetic analysis. The general scheme of the reactions is sketched. Thiyl radicals either equilibrate with RSSR^?- in reaction 5, RS^? + RS^- = RSSR^?-, or undergo intramolecular transformation via equilibrium 6, RS^? = ^?CR. At pH 10.5, equilibrium 6 is completely shifted to the right, resulting in α-aminoalkyl radical formation. The rate constants in the reaction scheme for cysteine, homocysteine, and glutathione were measured. With the rate constants obtained, the decay kinetics of RSSR^?- into ^?CR was simulated, and it agreed with that measured at 420 nm. At pH 10.5, the first-order rate constants for the transformation (k₆) were determined to be 2.5 × 10⁴, 1.8 × 10⁵ and 2.2 × 10⁵ s^-1 for cysteine, homocysteine, and glutathione, respectively. The rate constants for intermolecular hydrogen abstraction by thiyl radicals from α-amino C-H bonds of alanine and glycine were determined at the same pH to be 7.7 × 10⁵ and 3.2 × 10⁵ M^-1 s^-1, respectively. Thermodynamic estimation places the reduction potential E°(H₂NC(CO₂^-)CH₃^-, H⁺/H₂NCH(CO₂^-)CH₃) at ca. 1.22 V, which implies a rather weak tertiary C-H bond in the anion of α-amino acids. Thus, an intramolecular hydrogen abstraction mechanism for the transformation of thiyl radical to α-amino carbon-centered radical is postulated. Molecular geometry plays an important part in deciding the transformation rates (k₆,) of different thiyl radicals.