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 alpha-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 alpha-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 (k(6)) were determined to be 2.5 x 10(4), 1.8 x 10(5) and 2.2 x 10(5) s(-1) for cysteine, homocysteine, and glutathione, respectively. The rate constants for intermolecular hydrogen abstraction by thiyl radicals from alpha-amino C-H bonds of alanine and glycine were determined at the same pH to be 7.7 x 10(5) and 3.2 x 10(5) M(-1) s(-1), respectively. Thermodynamic estimation places the reduction potential E degrees(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 alpha-amino acids. Thus, an intramolecular hydrogen abstraction mechanism for the transformation of thiyl radical to alpha-amino carbon-centered radical is postulated. Molecular geometry plays an important part in deciding the transformation rates (k(6)) of different thiyl radicals.