Carboxylate as the Protonation Site in (Peroxo)diiron(III) Model Complexes of Soluble Methane Monooxygenase and Related Diiron Proteins

Abstract

Dioxygen activation by carboxylate-bridged diiron enzymes is involved in essential biological processes ranging from DNA synthesis and hydrocarbon metabolism to cell proliferation.1-3 The carboxylate-bridged diiron superfamily of proteins includes ribonucleotide reductase (RNR),4 Δ9 desaturase,5 bacterial multicomponent monooxygenases (BMMs),6,7 and most recently human deoxyhypusine hydroxylase (hDOHH).3 In all of these systems, the O2 reduction step proceeds through a (peroxo)- diiron(III) intermediate in which the resulting peroxo ligand is proposed to bridge two iron atoms in a μ-1,2 or μ-η2η2 coordination mode.8-10 Extensive studies of soluble methane monooxygenase (sMMO), a BMM family member that oxidizes methane to methanol, reveal that the generation and activation of Fe2O2 units requires protons.11,12 Given the complexity of protein environments, identifying the sites involved in such proton translocation processes and their effect on O2 activation is not a trivial undertaking.