TY - JOUR
T1 - Oxygen Activation and Radical Transformations in Heme Proteins and Metalloporphyrins
AU - Huang, Xiongyi
AU - Groves, John Taylor
N1 - Funding Information:
Xiongyi Huang received his B.S. degree in chemistry in 2010 from University of Science and Technology of China (USTC), where he performed undergraduate research in computational chemistry under the guidance of Prof. Yao Fu and Prof. Jing Shi. He received his Ph.D. in 2016 at Princeton University with Prof. John T. Groves. His Ph.D. work mainly focused on developing new synthetic strategies for the construction of aliphatic C−halogen, C−F, and C−N bonds using biomimetic manganese catalysts. While at Princeton, Xiongyi was a recipient of the HHMI International Student Research Fellowship (2013−2015) and the 2016 Chinese Government Award for Outstanding Students Abroad. He is currently an NIH Ruth L. Kirschstein postdoctoral fellow in the laboratory of Prof. Frances H. Arnold at Caltech, where he works on developing new enzymatic reactions via directed evolution.
Funding Information:
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 functional-ization 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
Funding Information:
by the National Institutes of Health (2R37 GM036298). X.H. thanks Merck, Inc., the Howard Hughes Foundation, and NIH (Award F32GM125231) for fellowship support.
Publisher Copyright:
© 2017 American Chemical Society.
PY - 2018/3/14
Y1 - 2018/3/14
N2 - 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 O2 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 O2-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 O2 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.
AB - 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 O2 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 O2-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 O2 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.
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U2 - 10.1021/acs.chemrev.7b00373
DO - 10.1021/acs.chemrev.7b00373
M3 - Review article
C2 - 29286645
AN - SCOPUS:85043775390
SN - 0009-2665
VL - 118
SP - 2491
EP - 2553
JO - Chemical Reviews
JF - Chemical Reviews
IS - 5
ER -