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

Abstract

This study evaluates the reaction of a biomimetic heme–peroxo–copper complex, {[(DCHIm)(F8)-FeIII]–(O22−)–[CuII(AN)]}+ (1), with a phenolic substrate, involving a net H-atom abstraction to cleave the bridging peroxo O–O bond that produces FeIV=O, CuII—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 OCu 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.

NRVS Studies of the Peroxide Shunt Intermediate in a Rieske Dioxygenase and Its Relation to the Native FeII O2 Reaction

“…38 The Gibbs free energy of protonating the guanidine group of Arg312 is −275 kcal/mol, 10 kcal/mol more favorable than bulk solvent. 80 It was found that deprotonating BZDOp and oxidizing it by one electron to an S = 2 Fe III –O 2 •− species (the lowest energy superoxo, vide infra) is unfavorable by 129.3 kcal/mol if the proton goes to solvent, or 119.3 kcal/mol if the proton goes to the guanidine group. The net thermodynamics of converting BZDOp to a superoxo Rieske red species are thus +43.2 kcal/mol (H + from solvent) or +33.2 kcal/mol (H + from Arg + ).…”

Influence of the distal guanidine group on the rate and selectivity of O2 reduction by iron porphyrin

“…The O-O bond cleavage in heme/Cu systems can be further enhanced by Hbonding to a bridging Fe-O-O-Cu peroxide. 39 The same is most conveniently achieved in mononuclear porphyrins by introducing protonated basic groups that can form H-bonds as well as translocate protons to the distal oxygen of the bound peroxide ( Fig. 8E and Table 2, row 5).…”

Synthetic Fe/Cu Complexes: Toward Understanding Heme-Copper Oxidase Structure and Function

“…883,884,892–894 it has been ruled out in the reaction of CcO with dioxygen, based on vibrational data and recent calculations which state that it is energetically less favorable to oxidize the porphyrin than nearby residues, specifically Tyr244. 322,747,887,891,895…”