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Oxygen Activation and Radical Transformations in Heme Proteins and Metalloporphyrins

Huang, Xiongyi and Groves, John T. (2018) Oxygen Activation and Radical Transformations in Heme Proteins and Metalloporphyrins. Chemical Reviews, 118 (5). pp. 2491-2553. ISSN 0009-2665. PMCID PMC5855008.

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As a result of the adaptation of life to an aerobic environment, nature has evolved a panoply of metalloproteins for oxidative metabolism and protection against reactive oxygen species. Despite the diverse structures and functions of these proteins, they share common mechanistic grounds. An open-shell transition metal like iron or copper is employed to interact with O_2 and its derived intermediates such as hydrogen peroxide to afford a variety of metal–oxygen intermediates. These reactive intermediates, including metal-superoxo, -(hydro)peroxo, and high-valent metal–oxo species, are the basis for the various biological functions of O_2-utilizing metalloproteins. Collectively, these processes are called oxygen activation. Much of our understanding of the reactivity of these reactive intermediates has come from the study of heme-containing proteins and related metalloporphyrin compounds. These studies not only have deepened our understanding of various functions of heme proteins, such as O2 storage and transport, degradation of reactive oxygen species, redox signaling, and biological oxygenation, etc., but also have driven the development of bioinorganic chemistry and biomimetic catalysis. In this review, we survey the range of O_2 activation processes mediated by heme proteins and model compounds with a focus on recent progress in the characterization and reactivity of important iron–oxygen intermediates. Representative reactions initiated by these reactive intermediates as well as some context from prior decades will also be presented. We will discuss the fundamental mechanistic features of these transformations and delineate the underlying structural and electronic factors that contribute to the spectrum of reactivities that has been observed in nature as well as those that have been invented using these paradigms. Given the recent developments in biocatalysis for non-natural chemistries and the renaissance of radical chemistry in organic synthesis, we envision that new enzymatic and synthetic transformations will emerge based on the radical processes mediated by metalloproteins and their synthetic analogs.

Item Type:Article
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URLURL TypeDescription CentralArticle
Huang, Xiongyi0000-0001-7156-8881
Groves, John T.0000-0002-9944-5899
Additional Information:© 2017 American Chemical Society. This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes. Special Issue: Oxygen Reduction and Activation in Catalysis. Received: June 21, 2017; Published: December 29, 2017. We are deeply indebted to our co-workers at Princeton University and at the University of Michigan in the early years, for their imaginative and energetic contributions to the work from our laboratories described herein. We are also grateful for the continuous support of this research by federal granting agencies. Research directed toward C–H oxidative functionalization was supported by the U.S. National Science Foundation Awards CHE-1148597 and CHE-1464578 and by the Center for Catalytic Hydrocarbon Functionalization, an Energy Frontier Research Center, U.S. Department of Energy, Office of Science, Basic Energy Sciences, under Award DESC0001298. Cytochrome P450 and APO enzymology has been supported by the National Institutes of Health (2R37 GM036298). X.H. thanks Merck, Inc., the Howard Hughes Foundation, and NIH (Award F32GM125231) for fellowship support. The authors declare no competing financial interest.
Funding AgencyGrant Number
Department of Energy (DOE)DE-SC0001298
NIH2R37 GM036298
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
NIH Postdoctoral FellowshipF32GM125231
Issue or Number:5
PubMed Central ID:PMC5855008
Record Number:CaltechAUTHORS:20180102-132213444
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Official Citation:Oxygen Activation and Radical Transformations in Heme Proteins and Metalloporphyrins. Xiongyi Huang and John T. Groves. Chemical Reviews 2018 118 (5), 2491-2553. DOI: 10.1021/acs.chemrev.7b00373
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:84032
Deposited By: George Porter
Deposited On:02 Jan 2018 21:43
Last Modified:14 Apr 2020 22:13

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