Kinetics and Mechanism of Hydroxyl Radical and OH-adduct Radical Reactions with Nitroxides and With Their Hydroxylamines
A Samuni, A Russo, J B. Mitchell, M C. Krishna, Pedatsur Neta, S Goldstein
The stable nitroxide radicals, such as 2,2,6,6-tetramethylpiperidinoxyl (TPO) and 4-OH-2,2,6,6-tetramethylpiperidinoxyl (TPL), are potent antioxidants and among the most effective non-thiol radioprotectants, although the reported rate constants of their reactions with OH radicals (3 x 109 L mol-1 s-1) are lower than those of typical phenolic antioxidants or thiols. Moreover, their reduced form, which is a better reductant, has no radioprotective effect. To measure the rate constants for reaction of OH radicals with the nitroxides (TPO and TPL) and the hydroxylamine (TPLH), steady-state and pulse radiolysis methods were utilized. Competition kinetics with SCN- in pulse radiolysis give rate constants kOH+TPO = (1.6 0.3) x 1010 L mol-1 s-1 and kOH+TPL = (1.75 0.3) x 1010 L mol-1 s-1, considerably higher than reported before. A much lower value is found for the hydroxylamine, kOH+TPLH = (2.4 0.4) x 109 L mol-1 s-1. This lower reactivity may partly account for the lower radioprotective activity. Competition kinetics with benzoate and terephthalate in steady-state radiolysis are complicated by the need to oxidize the transient OH-adducts into stable, and generally fluorescent, phenolic products. Nitroxides are found to affect aromatic hydroxylation through two opposing pathways: (a) fast oxidation of the OH-adducts, leading to an increase in yield at low [TPL], and (b) competition for OH radicals, leading to a decrease in yield at high [TPL]. Pathway (a) is more effective with TPL than with the commonly used ferricyanide and the rate constant of nitroxide with the OH adduct of terephthalate was determined by pulse radiolysis to be (1 0.15) x 107 L mol-1 s-1. Thus, nitroxide at micromolar concentrations effectively prevents dimerization of the OH-adducts and permits a valid use of aromatic hydroxylation a marker for OH formation.
, Russo, A.
, Mitchell, J.
, Krishna, M.
, Neta, P.
and Goldstein, S.
Kinetics and Mechanism of Hydroxyl Radical and OH-adduct Radical Reactions with Nitroxides and With Their Hydroxylamines, Journal of the American Chemical Society
(Accessed June 10, 2023)