Reactions of a free radical intermediate in the oxidation of amodiaquine.

One electron oxidation of the antimalarial drug amodiaquine by inorganic radicals was investigated by pulse radiolysis. A transient species was observed and identified as the semiiminoquinone radical, which has recently been implicated in the toxicity of amodiaquine. Pulse radiolysis was used to determine the reactivity of this radical. In the absence of other solutes it decays rapidly in a second order process. No reaction between the semiiminoquinone radical and oxygen could be observed. In the presence of ascorbate or a phenolic antioxidant (Trolox C) the semiiminoquinone radical was rapidly repaired. Similar reductants have been reported (Maggs JL et al., Biochem Pharmacol 37: 303-311, 1988) to inhibit irreverisble protein binding during amodiaquine autoxidation, and the present results support the involvement of the radical during these reactions.