Copper Peroxide Bioinorganic Chemistry: From Metalloenzymes to Bioinspired Synthetic Systems

Abstract

During the last few decades, copper‐dioxygen chemistry has emerged as a new and very active field of (bio)inorganic relevance. Highlighted herein are the major findings, including the principles of dioxygen activation in metal‐containing proteins along with characterization and reactivity of natural copper‐peroxo systems which are derived from reaction of molecular oxygen with copper(I) active‐site centers. Inspired by the varied array of copper proteins‐enzymes which have been characterized, synthetic bioinorganic researchers have developed model systems which are amenable to facilitating the electron‐transfer and atom‐transfer chemistry which pervades dioxygen binding to copper complexes found in various oxidation states (+1 to +3). These studies have provided for new coordination chemistry of fundamental importance. In addition, significant contributions concerning the identity of biological or chemical reactive intermediates and insights into copper enzyme reaction mechanisms have been made. Taking advantage of this rich redox chemistry, synthetic methods combining copper and O2 (or H2O2) have been explored by organic/inorganic chemists, seeking to employ this earth abundant element to replace routes now usually carried out with precious (expensive/non‐benign) metals, developing green, sustainable and selective oxidative processes.

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

“…1108 With increasing heme E o of the variants, O 2 -reduction activity and selectivity both improved, with the diformyl version showing a more than 5-fold increase over the initial F33Y-Cu B Mb (Figure 140, bottom) and remaining active for over 1000 turnovers. 1107 Electron flux to the active site in CcO has been proposed to be a rate-limiting and product-directing factor during enzymatic turnover, 679,876,1109 and the results from these experiments with engineered Mbderived mimics of CcO suggest that the heme E o is so positive in CcO to render it a better electron acceptor and thus able to drive O 2 -reduction. Interestingly, analogous transformations in WT-Mb also showed increased rates of O 2 -reduction; however, they also resulted in higher ratios of ROS formation, implicating the roles of H-bonding, Cu B , and proximal Tyr in selectivity (vide infra).…”

“…The structural variety of active sites and diverse interactions with dioxygen make copper-containing enzymes appealing targets for bioinspired model chemistry. , In synthetic inorganic systems, the chemist can control aspects of the copper ion coordination sphere, such as ligand denticity and donating ability, coordination geometry, and second coordination sphere interactions like hydrogen-bonding. In doing so, it is possible to investigate the reactivity of such systems with dioxygen, as different types of Cu n -O 2 adducts display unique/characteristic spectroscopic features (UV–vis, EPR, and rR spectroscopy, vide infra ).…”

“…713 While Cu II/III -OOR species have been shown to be active in substrate oxidation reactions, they are less relevant to the focus of this review, and therefore, we direct the interested reader to other recent reviews on the subject. 18,610,679 Instead, here we will discuss synthetic copper-hydroperoxides, which are proposed to be reactive intermediates in various O 2 -activating mononuclear copper enzymes (vide supra) and since a heme−Cu bridging hydroperoxide has been considered computationally as a potential fleeting but very important intermediate in the catalytic cycle of HCOs. As with other Cu-oxy species, the ligand structure (coordination geometry, ligand denticity, type, and sterics), electronics (reduction potential), and secondary coordination sphere (H-bonding) have profound effects on the formation, stability, and reactivity of copper(II) hydroperoxides.…”