Pulse radiolysis studies on the oxidation of OH˙ radical-damaged DNA by nitroquinolines in aqueous solution

Abstract

The reactions of nitroquinolines with radical sites on DNA, formed by OH˙ radical attack in aqueous solution, have been studied. It is found that the small concentrations of compound, unbound to DNA, oxidise the essentially immobile DNA radicals with diffusion-controlled rate constants of ca. 5 × 10⁹ dm³ mol^–1 s^–1to form absorbing radical anions. Oxidation of the radical sites by the proportion of the compounds bound to DNA does not occur, except to a small extent in the case of the 6-nitro regioisomer. Calculations based on the measured intrinsic association constant and migration rate along DNA of the 6-nitro regioisomer yield a jump time between neighbouring sites on the DNA of 2.76 ns. Competition studies between such compounds which bind to DNA and xenobiotica for OH˙ radical-damaged sites on DNA is illustrated by studies with three thiol compounds which yield second-order rate constants for repair of the DNA radicals, through H-atom donation; glutathione, 1.2 × 10⁶ dm³ mol^–1 s^–1, cysteine, 6 × 10⁶ dm³ mol^–1 s^–1 and cysteamine, 1.6 × 10⁸ dm³ mol^–1 s^–1.