A density functional investigation of hydrogen peroxide activation by high-valent heme centers: implications for the catalase catalytic cycle

Abstract

Catalases employ a tyrosinate-ligated ferric heme in order to catalyze the dismutation of hydrogen peroxide to O2 and water. In the first half of the catalytic cycle, H2O2 oxidizes Fe(III) to the formally Fe(V) state commonly referred to as Compound I. The second half of the cycle entails oxidation of a second hydrogen peroxide molecule by Compound I to dioxygen. The present study employs density functional (DFT) calculations to examine the nature of this second step of the catalatic reaction. In order to account for the unusual choice of tyrosinate as an axial ligand in catalases, oxidation of hydrogen peroxide by an imidazole-ligated Compound I is also examined, bearing in mind that imidazole-ligated hemoproteins such as myoglobin or horseradish peroxidase tend to display little, if any, catalatic activity. Furthermore, in order to gauge the importance of the cation radical of Compound I in peroxide activation, the performance of Compound II (the one-electron reduced version of Compound I, formally Fe(IV) ), is also examined. It is found that hydrogen peroxide oxidation occurs in a quasi-concerted manner, with two hydrogen-atom transfer reactions, and that the tyrosinate ligand is in no way required at this stage. We propose that the role of the tyrosinate is purely thermodynamic, in avoiding accumulation of the much less peroxide-reactive ferrous form in vivo – all in line with the predominantly thermodynamic role of the cysteinate ligands in enzymes such as cytochromes P450.