Bio-inspired Mononuclear Nonheme Metal Peroxo Complexes

Abstract
Metalloenzymes utilize inexpensive and earth-abundant transition metal ions as important co-factors to enable binding of a dioxygen molecule so that it can be used in various biological metabolisms. For many important enzymatic reactions, dioxygen binding and activation is the fundamental process used to generate chemically reactive metal–oxygen intermediates. During past decades, a variety of hypothetical metal–oxygen adducts have been proposed as key intermediates in the catalytic reaction of metalloenzymes. For example, metal peroxo species have been considered and sometimes directly captured spectroscopically and crystallographically at the active site of several metalloenzymes including Rieske dioxygenase, deformylase and superoxide dismutase. To understand the chemical properties and reactivities of the metal peroxo intermediates, synthetic model chemistry has been advanced with numerous ligand systems and central metal ions. The successful synthesis of well-characterized metal peroxo compounds has allowed us to acquire deep insights into the mechanisms of such enzymatic reactions. In this review, we encompass overall studies on the nonheme first-row transition metal peroxo complexes (M = Mn, Fe, Co, Ni and Cu) with physicochemical characterization and structural information. The chemical reactivities of the metal peroxo complexes relevant to the biological system are also presented. Nucleophilic aldehyde deformylation has become a representative reaction mediated by the metal peroxo intermediates, and recent findings have revealed unique reaction mechanisms such as nitrile activation. Furthermore, rate-determining H atom abstraction has also been suggested in the current study on the aldehyde deformylation. Extrinsic factors to control the chemical properties and reactivities of the metal peroxo complexes have recently been accomplished through adding the redox inactive metal ion and modifying the ligand topology. It is hoped that the comprehensive knowledge presented in this review will help to broaden and deepen our understanding of the metal peroxo intermediates and be useful to understand enzyme mechanisms and to develop bioinspired catalysts.

More than 40% of enzymes in the oxygen organism are metal enzymes that contain metal ions as essential. They use molecules to form metal-activated oxygen intermediates to remove the toxicity of substances or to synthesize necessary biomolecules. In particular, metal-peroxo species have been observed as an important reaction intermediate in several metal enzymes.

A team led by Professor Jaeheung Cho of the Department of Chemistry at UNIST published a comprehensive review paper, collecting all the results of research on simulated compounds of ‘metal-peroxin species’, one of the metal-active oxygen intermediates. Through this paper, it is expected to make a key contribution to improving understanding of metal enzymes and developing biomimetic catalysts.

Metal-peroxinoma has been proposed as a reaction intermediate that oversees important reactions in various metal enzymes such as male aldehyde depomylase and naphthalene discretase. In order to accurately understand the spectroscopic properties and reaction mechanisms of these metal-activated oxygen species, simulated compounds that mimic the active site of metal enzymes have been reported over the past few decades.

First, the research team collected all the papers of various metal-peroxo species that have been revealed so far and classified them by metal. In particular, metal-peroxone species using manganese, iron, cobalt, nickel, copper, etc., which are first-cycle transition metals that are closely used in living things, have been discussed.

“Recently, metal-peroxin species have been actively researched and important characteristics have been discovered,” said Donghyun Jeong (Department of Chemistry, UNIST), the first author of this study. “This paper systematically categorizes and organizes vast research topics that have been conducted for decades in the field of bioinorganic chemistry.”

After that, the metal-peroxo species synthesized through biomimetic analysis, the ligand and complex synthesis methods utilized, the characteristics confirmation through various physicochemical techniques, and the basic research on reactivity with substrates were summarized. In addition, important information for understanding metal enzymes was clearly summarized, suggesting prospects for subsequent studies of metal-activated oxygen species.

“This paper allows us to understand the flow of metal-peroxo species research so far,” said Professor Choi. “We expect it to be of great help in presenting follow-up research directions, including the development of biomimetic catalysts.”

This study has been participated by Donghyun Jeong from the Department of Chemistry at UNIST, as first author. Their findings have been published in the January 2023 issue of Coordination Chemistry Reviews, a renowned journal in the field of Chemistry. This study has been supported by the National Research Foundation of Korea (NRF) and the Korean government (MSIT).

Journal Reference
Donghyun Jeong, Joan Selverstone Valentine, Jaeheung Cho, “Bio-inspired mononuclear nonheme metal peroxo complexes: Synthesis, structures and mechanistic studies toward understanding enzymatic reactions,” Coord. Chem. Rev., (2023)