Theoretical Study of O₂ Reduction and Water Oxidation in Multicopper Oxidases

Abstract

Recent electrochemical experiments have shown that the reduction of O 2 can be driven backward to water oxidation, which is the first case that has been successfully demonstrated for an enzyme. To understand this ability of the enzyme, both the forward reduction and backward oxidation have been studied here. For the forward reaction, a mechanism similar to earlier studies was obtained. All steps of the full catalytic cycle were obtained for the first time, and it was shown that the explicit reduction steps contribute significantly to the rate-limiting step of the O–O bond cleavage. For the backward oxidation reaction, it was found that the mechanism of the O–O bond formation is not just the reverse of the reduction step where the O–O bond is cleaved for a protonated peroxide. The formation of two fully deprotonated oxo groups was found to be important, which leads to a large radical character for one of the oxo groups. For this possibility, it is important that the p K a of the water bound to the cofactor is quite high.

A quantum chemical approach for the mechanisms of redox-active metalloenzymes

“…The mechanism for reduction was found 66 to be the same as in the previous studies. 68 O 2 was found to be bound in the center of the cluster with bidentate bonding to one of the coppers and single bonds to the other ones.…”

“… 65 It was therefore of high interest to investigate how the present methodology works in those cases. 66 Recent electrochemical experiments was another reason for a study of these systems. 67 Interestingly, it was shown that O 2 reduction could actually be reversed to water oxidation for an enzyme of this type, which was the first case this had been shown for an enzyme.…”

Investigation of Water Splitting Reaction by a Multicopper Oxidase through X‐ray Absorption Nanospectroelectrochemistry

“…The few electrochemical investigations reported so far do not address those enzymes' mechanistic aspects of the WOR, [3,8] and only theoretical results using the density functional theory (DFT) have been recently presented. [4] Recently, we conducted an X-ray absorption spectroelectrochemistry experiment to investigate the performance of a copper-containing oxidoreductase enzyme as an ORR catalyst. [12] In the presence of O 2 , the BOD cofactor containing four copper ions requires an overpotential of 150 mV to be reduced in relation to that in the absence of O 2 .…”

“…[1,2] The molecular oxygen reduction (ORR) and the water oxidation reactions (WOR), catalyzed by multicopper oxidases, can be applied toward the generation of renewable and sustainable energy. [3][4][5] Although most redox enzymes are traditionally referred to In this context, in situ X-ray absorption spectroelectrochemistry with nanoscale resolution is a powerful tool as it can provide electronic and local atomistic information of the metal active sites of enzymes under real practical reaction conditions and concomitantly to an electrochemical control, without interferences of the enzyme shell and solvent, as well as, can enable to obtain thermodynamic parameters from the reaction. [12,14] Particularly, for investigating the oxidation state and electronic structure of the Cu atoms within BOD, the X-ray absorption near-edge spectra (XANES) at the Cu K-edge were recorded.…”

“…[ 1,2 ] The molecular oxygen reduction (ORR) and the water oxidation reactions (WOR), catalyzed by multicopper oxidases, can be applied toward the generation of renewable and sustainable energy. [ 3–5 ] Although most redox enzymes are traditionally referred to catalyze an irreversible redox reaction in a specific condition, hydrogenases, [ 6 ] formate dehydrogenase, [ 7 ] and some multicopper oxidases [ 3,8 ] have been demonstrated to be reversible catalysts at small overpotentials. In the case of multicopper oxidases, this versatility can be attributed to the presence of three‐dimensional copper sites in the highly stable protein structure.…”