Heme-copper/dioxygen adduct formation, properties, and reactivity

This Account focuses on our recent developments in synthetic heme/copper/O 2 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 O 2 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 O 2-derived heme-Cu bridging group depends upon the copper-ligand environment, resulting in micro-(O 2 (2-)) side-on to Fe (III) and end-on to Cu (II) (micro-eta (2):eta (1)) binding for cases having N 4 tetradentate ligands but side-on/side-on (micro-eta (2):eta (2)) micro-peroxo coordination with tridentate copper chelates. The dynamics of the generation of Fe (III)-(O 2 (2-))-Cu (II) complexes are known in some cases, including the initial formation of a short-lived superoxo (heme)Fe (III)(O 2 -) 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.