The products of electro- and photochemical oxidation of 2-hydroxyacridinone, the reference compound of antitumor imidazoacridinone derivatives

Abstract

Electrochemical oxidation of 2-hydroxyacridinone, the reference compound of antitumor imidazoacridinone derivatives, was studied by cyclic voltammetry (CV), spectroelectrochemical methods and controlled potential electrolysis. The photochemical oxidation was also investigated. The studies aimed to elucidate the pathway of the oxidative metabolic activation of antitumor hydroxyacridinones under biological conditions. The cyclic voltammogram at a glassy-carbon electrode in water, pH 7.4 showed the electrochemical oxidation to be an irreversible process. The main peak potential ( E p) is pH-dependent in the range of 3–10 pH units. The spectroelectrochemical experiments performed at pH 7.4 revealed that four products of electrochemical and chemical reactions were formed during the forward potential scan and they were reduced during the reverse scan. One product of this reduction represents the reversible process. Two products of the oxidative transformation of 2-hydroxyacridinone were identified by means of MS and NMR spectroscopy. The first one, p1, turned out to be a dimer: 1,1-bi(2-hydroxyacridinone), whereas the second one, p2, was an extremely unstable orthoquinone derivative. Cyclic voltammograms of p1 and p2 allowed us to identify the current peaks observed in the voltammograms of the substrate. Two pathways of 2-hydroxyacridinone electrooxidation were proposed. The contribution of each pathway to the formation of products p1 and p2 depended on the electrochemical potential (Ecp) and pH conditions. The proposed pathways were discussed with respect to the metabolic activation of hydroxyacridinones in the organism. It was suggested that the electrooxidation might be a suitable method for the synthesis of adducts between antitumor hydroxyacridinones and DNA.