Dioxygen reactivity of copper and heme-copper complexes possessing an imidazole-phenol cross-link

Recent spectroscopic, kinetics, and structural studies on cytochrome c oxidases (CcOs) suggest that the histidine-tyrosine cross-link at the heme a(3)-Cu-B binuclear active site plays a key role in the reductive O-2-cleavage process. In this report, we describe dioxygen reactivity of copper and heme/Cu assemblies in which the imidazole-phenol moieties are employed as a part of copper ligand (LOH)-O-N4 (2- 4-[2-(bis-pyridin-2-ylmethyl-amino)-ethyl]-imidazol-1-yl}-4,6-di-tert-butyl-phenol). Stopped-flow kinetic studies reveal that low-temperature oxygenation of [Cu-I((LOH)-O-N4)](+) (1) leads to rapid formation of a copper-superoxo species [Cu-II((LOH)-O-N4)(O-2(-))](+) (1a), which further reacts with 1 to form the 2:1 Cu:O-2 adduct, peroxo complex [{Cu-II((LOH)-O-N4)}(2)(O-2(2-))](2+) (1b). Complex 1b is also short-lived, and a dimer Cu(II)-phenolate complex [CuII((LO-)-O-N4)](2)(2+) (1c) eventually forms as a final product in the later stage of the oxygenation reaction, Dioxygen reactivities of 1 and its anisole analogue [Cu-I((LOMe)-O-N4)](+) (2) in the presence of a heme complex (F-8)Fe-II (3) (F-8 = tetrakis(2,6,-difluorotetraphenyl)-porphyrinate) are also described. Spectroscopic investigations including UV-vis, H-1 and H-2 NMR, EPR, and resonance Raman spectroscopies along with spectrophotometric titration reveal that low-temperature oxygenation of 1/3 leads to formation of a heme-peroxo-copper species [(F-8)Fe-III-(O-2(2-))-Cu-II((LOH)-O-N4)](+) (4), v((O-O)) = 813 cm(-1). Complex 4 is an S = 2 spin system with strong antiferromagnetic coupling between high-spin iron(III) and copper(II) through a bridging peroxide ligand. A very similar complex [(F-8)Fe-III-(O-2(2-))-Cu-II((LOMe)-O-N4)](+) (5) (v((O-O)) = 815 cm(-1)) can be generated by utilizing the anisole compound 2, which indicates that the cross-linked phenol moiety in 4 does not interact with the bridging peroxo group between heme and copper. This investigation thus reveals that a stable heme-peroxo-copper species can be generated even in the presence of an imidazole-phenol group (i.e., possible electron/proton donor source) in close proximity. Future studies are needed to probe key factors that can trigger the reductive O-O cleavage in CcO model compounds.