Various strategies for obtaining oxidative artificial hemoproteins with a catalytic oxidative activity: from "Hemoabzymes" to "Hemozymes"?

Abstract

The design of artificial hemoproteins that could lead to new biocatalysts for selective oxidation reactions using clean oxidants such as O 2 or H 2 O 2 under ecocompatible conditions constitutes a really promising challenge for a wide range of industrial applications. In vivo, such reactions are performed by heme-thiolate proteins, cytochromes P450, that catalyze the oxidation of drugs by dioxygen in the presence of electrons delivered from NADPH by cytochrome P450 reductase. Several strategies were used to design new artificial hemoproteins to mimic these enzymes, that associate synthetic metalloporphyrin derivatives to a protein that is supposed to induce a selectivity in the catalyzed reaction. A first generation of artificial hemoproteins or "hemoabzymes" was obtained by the non-covalent association of synthetic hemes such as N-methyl-mesoporphyrin IX, Fe(III) -α3β-tetra-o-carboxyphenylporphyrin or microperoxidase 8 with monoclonal antibodies raised against these cofactors. The obtained antibody-metalloporphyrin complexes displayed a peroxidase activity and some of them catalyzed the regio-selective nitration of phenols by H 2 O 2/ NO 2 and the stereo-selective oxidation of sulphides by H 2 O 2. A second generation of artificial hemoproteins or "hemozymes", was obtained by the non-covalent association of non-relevant proteins with metalloporphyrin derivatives. Several strategies were used, the most successful of which, named "host-guest" strategy involved the non-covalent incorporation of metalloporphyrin derivatives into easily affordable proteins. The artificial hemoproteins obtained were found to be able to perform efficiently the stereoselective oxidation of organic compounds such as sulphides and alkenes by H 2 O 2 and KHSO 5.