Phenol-Induced O–O Bond Cleavage in a Low-Spin Heme–Peroxo–Copper Complex: Implications for O2 Reduction in Heme–Copper Oxidases

Journal of the American Chemical Society

5 years ago

Phenol-Induced O–O Bond Cleavage in a Low-Spin Heme–Peroxo–Copper Complex: Implications for O2 Reduction in Heme–Copper Oxidases

Edward I. Solomon, Kenneth D. Karlin, Suzanne M. Adam, Andrew W. Schaefer, Matthew T. Kieber-Emmons

This study evaluates the reaction of a biomimetic heme–peroxo–copper complex, {[(DCHIm)(F₈)Fe^III]–(O₂^2–)–[Cu^II(AN)]}⁺ (1), with a phenolic substrate, involving a net H-atom abstraction to cleave the bridging peroxo O–O bond that produces Fe^IV═O, Cu^II—OH, and phenoxyl radical moieties, analogous to the chemistry carried out in heme–copper oxidases (HCOs). A 3D potential energy surface generated for this reaction reveals two possible reaction pathways: one involves nearly complete proton transfer (PT) from the phenol to the peroxo ligand before the barrier; the other involves O–O homolysis, where the phenol remains H-bonding to the peroxo O_Cu in the transition state (TS) and transfers the H⁺ after the barrier. In both mechanisms, electron transfer (ET) from phenol occurs after the PT (and after the barrier); therefore, only the interaction with the H⁺ is involved in lowering the O–O cleavage barrier. The relative barriers depend on covalency (which governs ET from Fe), and therefore vary with DFT functional. However, as these mechanisms differ by the amount of PT at the TS, kinetic isotope experiments were conducted to determine which mechanism is active. It is found that the phenolic proton exhibits a secondary kinetic isotope effect, consistent with the calculations for the H-bonded O–O homolysis mechanism. The consequences of these findings are discussed in relation to O–O cleavage in HCOs, supporting a model in which a peroxo intermediate serves as the active H⁺ acceptor, and both the H⁺ and e^– required for O–O cleavage derive from the cross-linked Tyr residue present at the active site.

Publisher URL: http://dx.doi.org/10.1021/jacs.7b03292

DOI: 10.1021/jacs.7b03292