Radiolytically induced one-electron reduction of artemisinin in H₂O/ethanol (1:1 v/v) solution: a pulse radiolysis study.

Abstract

The aim was to obtain information on the one-electron reduction of the antimalarial natural drug artemisinin (ART). The pulse radiolysis of ART in H₂O/ethanol (EtOH) (1:1 v/v) solution was studied in the absence and presence of the so-called redox indicators N,N,N’,N’-tetramethyl-p-phenylenediamine (TMPD), Fe(CN)₆^4 −, 1,1′-dimethyl-4,4′-bipyridinium dichloride (methyl viologen, MV^2 +) and Fe(CN)₆^3 −. In an argon-purged solution, ART reacts with solvated electrons (e_s⁻) with k = 4.4 × 10⁹ dm³ mol^− 1 s^− 1 generating an absorption band rising in the ultraviolet region similar to the spectrum of the CH₃^•CHOH radical. The species originating from the reaction between ART and e_s⁻ do not show any appreciable reactivity toward Fe(CN)₆^4 −, TMPD, MV^2 + and Fe(CN)₆^3 −. The experiments performed in the presence of ART and MV^2 + have provided strong support to the idea that the first species obtained from the addition of the electron, which is believed to occur at the endoperoxide group level, undergoes a rapid (k on the order of 10⁸ s^− 1 or higher) intramolecular rearrangement to give species, most likely carbon-centred radicals, that show some reactivity towards the methyl viologen radical cation (MV^• +).