One-electron reduction of the antimalarial drug primaquine, studied by pulse radiolysis.

One-electron reduction of the antiparasitic drug primaquine has been studied by pulse radiolysis. Primaquine is reduced by the hydrated electron at neutral pH with a rate constant of (2.47 +/- 0.1) x 10(10) dm3mol-1s-1. Reduction by formate and isopropanol radicals is relatively slow (less than or equal to 10(7) dm3mol-1s-1) at neutral pH, but increases in rate with decreasing pH on protonation of the quinoline moiety. The one-electron reduction product form reaction of the hydrated electron with primaquine at neutral pH reacts with O2, benzyl viologen and NAD+ with rates of (1-2.3) x 10(9) dm3mol-1s-1. The relevance of these observations to the mechanisms proposed by Thornalley et al. (Biochem. Pharmacol. 32, 357, (1983] for oxygen free radical generation in solutions of NADPH and primaquine and the antiparasitic action of the drug is discussed.