Heme–Copper/Dioxygen Adduct Formation, Properties, and Reactivity

Abstract

This Account focuses on our recent developments in synthetic heme/copper/O₂ chemistry, potentially relevant to the mechanism of action of heme–copper oxidases (e.g., cytochrome c oxidase) and to dioxygen activation chemistry. Methods for the generation of O₂ adducts, which are high-spin heme(Fe^III)–peroxo–Cu^II complexes, are described, along with a detailed structural/electronic characterization of one example. The coordination mode of the O₂-derived heme–Cu bridging group depends upon the copper–ligand environment, resulting in μ-(O₂^2–) side-on to Fe^III and end-on to Cu^II (μ-η²:η¹) binding for cases having N₄ tetradentate ligands but side-on/side-on (μ-η²:η²) μ-peroxo coordination with tridentate copper chelates. The dynamics of the generation of Fe^III–(O₂^2–)–Cu^II complexes are known in some cases, including the initial formation of a short-lived superoxo (heme)Fe^III(O₂^•–) intermediate. Complexes with cross-linked imidazole–phenol “cofactors” adjacent to the copper centers have also been described. Essential investigations of heme–copper-mediated reductive O–O bond cleavage chemistry are ongoing.