The Autoxidation of the Reduced Forms of EO9

Abstract

The properties of the semiquinone radical from [3-hydroxy-5-aziridmyl-1-methyl-2-(1H-indole-4,7-indi one)-prop-β-en-α-ol], EO9, have been studied using pulse-radiolysis techniques. The reduction potential of the semiquinone of EO9 at pH 7.4, E(EO9/EO9⁻), is -253 ± 6 mV and hence this quinone can be readily reduced by one-electron reducing enzymes such as cytochrome P450 reductase and xanthine oxidase. However, the radical is unstable in the presence of oxygen (k = 1.3 ± 0.15 × 10⁸ M⁻¹ s⁻¹). The semiquinone radicals and the hydroquinone are in equilibrium, although the formation of the hydroquinone is favoured at physiologically relevant pH. The hydroquinone of EO9 is also unstable in the presence of oxygen and it is predicted that in fully aerated solutions, its half life is 1.5 ± 0.3 seconds. These results are discussed in view of the selective cytoxicity of EO9 and its ability to undergo bioreductive activation by one-electron reducing enzymes and DT-diaphorase.

Key Words:

• EO9
• semiquinone
• hydroquinone
• DT-diaphorase
• autoxidation
• pulse radiolysis