Dioxygen Activation by Nonheme Diiron Enzymes: Diverse Dioxygen Adducts, High-Valent Intermediates, and Related Model Complexes

Chem Rev. 2018 Mar 14;118(5):2554-2592. doi: 10.1021/acs.chemrev.7b00457. Epub 2018 Feb 5.

Abstract

A growing subset of metalloenzymes activates dioxygen with nonheme diiron active sites to effect substrate oxidations that range from the hydroxylation of methane and the desaturation of fatty acids to the deformylation of fatty aldehydes to produce alkanes and the six-electron oxidation of aminoarenes to nitroarenes in the biosynthesis of antibiotics. A common feature of their reaction mechanisms is the formation of O2 adducts that evolve into more reactive derivatives such as diiron(II,III)-superoxo, diiron(III)-peroxo, diiron(III,IV)-oxo, and diiron(IV)-oxo species, which carry out particular substrate oxidation tasks. In this review, we survey the various enzymes belonging to this unique subset and the mechanisms by which substrate oxidation is carried out. We examine the nature of the reactive intermediates, as revealed by X-ray crystallography and the application of various spectroscopic methods and their associated reactivity. We also discuss the structural and electronic properties of the model complexes that have been found to mimic salient aspects of these enzyme active sites. Much has been learned in the past 25 years, but key questions remain to be answered.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Catalytic Domain
  • Crystallography, X-Ray
  • Iron / chemistry*
  • Oxidation-Reduction
  • Oxidoreductases / chemistry
  • Oxidoreductases / metabolism*
  • Oxygen / chemistry
  • Oxygen / metabolism*
  • X-Ray Absorption Spectroscopy

Substances

  • Iron
  • Oxidoreductases
  • Oxygen