Why copper is preferred over iron for oxygen activation and reduction in haem-copper oxidases

Abstract

Heme-copper oxidase (HCO) catalyzes the natural reduction of oxygen to water using a heme-copper center. Despite decades of research on HCO's, the role of nonheme metal and Nature's choice of copper over other metals like iron remains unclear. Here, we use a biosynthetic model of HCO in myoglobin that selectively binds different nonheme metals to demonstrate 30-fold and 11-fold enhancements in oxidase activity of Cu- and Fe-bound HCO mimics respectively, as compared to Zn-bound mimics. Detailed electrochemical, kinetic and vibrational spectroscopic studies, in tandem with theoretical DFT calculations demonstrate that the nonheme metal not only donates electrons to oxygen but also activates it for efficient O-O bond cleavage. Furthermore, the higher redox potential of copper and the enhanced weakening of O-O bond from the higher electron density in the d-orbital of copper are central to its higher oxidase activity over iron. This work resolves a long-standing question in bioenergetics, and renders a chemical-biological basis for designing future oxygen reduction catalysts.

Activation of dioxygen by copper metalloproteins and insights from model complexes

“…Most recently, Bhagi-Damodaran et al reported on a study which reflects on why nature may have chosen copper as the non-heme metal in the O 2 reduction site of heme-copper oxidases [238]. In constructs related to those mentioned above, an Mb was engineered to contain a non-heme 3-His-1-Glu binding pocket for Zn, Fe or Cu (Fig.…”

“…The authors attributed this rate enhancement to the Cu ion center in Cu II -Fe B -Mb possessing a higher reduction potential relative to the non-heme Fe coordination moiety in Fe III -Fe B -Mb. This results in faster ET from an external reductant to the Cu ion within the hetero-binuclear center, corresponding to the overall rate-limiting step [238]. …”

“…Middle-Right imiTyrCu B Mb contains an additional histidine, and an unnatural histidine crosslinked to tyrosine in the distal binding pocket [237]. Right M II -Fe B Mb contains two additional histidines and a glutamate in the distal binding pocket [238]…”

Biomimetic Reactivity of Oxygen-Derived Manganese and Iron Porphyrinoid Complexes

“…11,12 Finally, the ability to encapsulate the metalloporphyin in artificial or engineered proteins has seen a recent surge in effort. 13-16 …”

Bimetallic organic frameworks derived CuNi/carbon nanocomposites as efficient electrocatalysts for oxygen reduction reaction

“…However, no studies have developed efficient nanocomposites that incorporate Cu and Ni as ORR catalysts. To the best of our knowledge, although Cu is not an active ORR catalyst compared to the most efficient non-noble materials, copper based enzymes are famous for their oxygen reduction reactivity [36][37][38][39]. On the other hand, the extensively-studied PtM (M is transition metal such as Ni, Fe, Co) [40][41][42] demonstrates enhanced kinetics of the ORR than the commercial Pt/C.…”