Mechanism and Catalytic Site Atlas

Introduction

The hydrogen peroxide substrate becomes bound to the oxidised [3,3] state of the Mn cluster via a terminal oxygen, replacing the nonbridging solvent (W3) on the Mn1 subsite. The [3,3] cluster has a diamagnetic ground state, associated with the bis-m-bridged dimanganese core structure. The bridging ligands act as proton acceptor sites in this reaction and support electronic coupling between the two Mn ions. Two-electron reduction of the terminally bound peroxide by the dinuclear Mn (III) complex results in the release of the dioxygen product. This step is facilitated by the two oxygen bridges (W1 and W2) that electronically couple the Mn ions. Glu 178 is involved in transferring the peroxidic protons to active site bases during turnover. These bases are likely to be the solvent molecules themselves, tightly coupling proton transfer to metal-centred redox. The cluster, now in a [2,2] reduced state has labile bridging groups, which allow substantial substitutional insertion of peroxide into a bridging position of the reduced complex in forming an m(1,1) hydroperoxy intermediate. Therefore, the peroxide replaces the relatively weakly bound, doubly protonated (aquo) bridge. The resulting m(1,1) bridging mode favours heterolytic peroxide cleavage due to polarization of the O-O bond, and is activated towards reoxidation of the dimanganese core. The O-O bond may be further activated by vic to gem isomerisation of the peroxide protons with the Glu 178 shuttle catalysing the proton rearrangement, protonating the nonbridging oxygen of the bound substrate. Loss of water regenerates the [3,3] state of the cluster.