Phenoxazinone synthase activity of a mononuclear cobalt(III) complex

Metalloenzymes that activate molecular oxygen possess great potential as catalyst for specific oxidation reactions and as guides for the development of efficient small molecule catalysts. These lowmolecular metal complexes serves as functional model and catalyze the same (or a closely related) reaction as does the metalloenzyme to be mimicked. In combination with the structural models which mimic various structural features, functional models constitute the basis for the modelling approach in the study of metalloenzymes, which regards metalloenzyme active sites as metal complexes embedded in a protein matrix. The study of biomimetic reactions catalyzed by functional metalloenzyme models helps to understand the mechanisms of metalloenzyme action and assists the design of metal complex catalysts for specific purposes (bioinspired catalysis). The enzyme, phenoxazinone synthase, a type 2 copper-containing oxidase (subunit molecular mass 88,000, 3.7 Cu per subunit) is naturally found in the bacterium Streptomyces antibioticus and has been cloned and over expressed in S. Lividians. This enzyme catalyzes the six electron oxidative coupling of two molecules of a substituted 2-aminophenol to the phenoxazinone chromophore (Scheme 1) in the final step in the biosynthesis of actinomycin D, namely, the oxidative condensation of two molecules of 3-hydroxy-4-methylanthranilic acid pentapeptide lactone to form actinocin (Scheme 2). Actinomycin D is clinically used to treat Wilm’s tumor, gestational choriocarcinoma, and other tumors. The synthesis and reactivity studies of transition metal complexes, as model compounds for metalloenzymes with oxidase (oxygenase) activity, are of particular interest for the development of bioinspired catalysts for oxidation reactions. Several copper(II), cobalt(II/III), manganese(II/IV), iron(III) complexes as functional models of phenoxazinone synthase have been reported. Herein, we report the phenoxazinone synthase activity of a trivalent cobalt(III) complex, [Co(HL)2] (OAc).H2O (1) [H2L = N-(2-hydroxyethyl)3-methoxysalicylaldimine], which has been structurally characterized by X-ray data earlier (Fig. 1). (1) behaves as an effective catalyst towards oxidative dehydrogenation of o-aminophenol (OAPH) to 2-aminophenoxazine-3-one (APX) in aerial oxygen.