From "hemoabzymes" to "hemozymes": towards new biocatalysts for selective oxidations

The design of artificial hemoproteins that could catalyze selective oxidations using clean oxidants such as O 2 or H 2 O 2 under ecocompatible conditions constitutes a real challenge for a wide range of industrial applications. In vivo , such reactions are performed by heme-thiolate proteins, cytochromes P450, which catalyze the oxidation of substrates by dioxygen in the presence of electrons delivered from NADPH by cytochrome P450 reductase. Several strategies were used to design new artificial hemoproteins that mimic these enzymes. The first one involved the non-covalent association of synthetic hemes with monoclonal antibodies raised against these cofactors. This led to the first generation of artificial hemoproteins or "hemoabzymes" that displayed a peroxidase activity, and in some cases catalyzed the regioselective nitration of phenols by H 2 O 2 /NO 2 and the stereoselective oxidation of sulfides by H 2 O 2 . The second one involved the non-covalent association of easily affordable non-relevant proteins with metalloporphyrin derivatives, using either the "Trojan Horse strategy" or the "host-guest" strategy. This led to a second generation of artificial hemoproteins or "hemozymes", some of which were found able to catalyze the stereoselective oxidation of organic compounds such as sulfides and alkenes by H 2 O 2 and KHSO 5 . Two generations of artificial hemoproteins have been obtained: "hemoabzymes", by non-covalent association of synthetic hemes with monoclonal antibodies raised against these cofactors and "hemozymes", by non-covalent association of non-relevant proteins with metalloporphyrin derivatives. A review of the different strategies employed as well as their structural and catalytic properties is presented here.