Arene activation by a nonheme iron(III)–hydroperoxo complex: pathways leading to phenol and ketone products

  • Abayomi S. Faponle
  • Frédéric Banse
  • Sam P. de Visser
Original Paper


Iron(III)–hydroperoxo complexes are found in various nonheme iron enzymes as catalytic cycle intermediates; however, little is known on their catalytic properties. The recent work of Banse and co-workers on a biomimetic nonheme iron(III)–hydroperoxo complex provided evidence of its involvement in reactivity with arenes. This contrasts the behavior of heme iron(III)–hydroperoxo complexes that are known to be sluggish oxidants. To gain insight into the reaction mechanism of the biomimetic iron(III)–hydroperoxo complex with arenes, we performed a computational (density functional theory) study. The calculations show that iron(III)–hydroperoxo reacts with substrates via low free energies of activation that should be accessible at room temperature. Moreover, a dominant ketone reaction product is observed as primary products rather than the thermodynamically more stable phenols. These product distributions are analyzed and the calculations show that charge interaction between the iron(III)–hydroxo group and the substrate in the intermediate state pushes the transferring proton to the meta-carbon atom of the substrate and guides the selectivity of ketone formation. These studies show that the relative ratio of ketone versus phenol as primary products can be affected by external interactions of the oxidant with the substrate. Moreover, iron(III)–hydroperoxo complexes are shown to selectively give ketone products, whereas iron(IV)–oxo complexes will react with arenes to form phenols instead.


Biomimetic models Chemoselectivity Aromatic hydroxylation Enzyme models Cytochrome P450 


Cpd 0

Compound 0

Cpd I

Compound I


Density functional theory


Kinetic isotope effect






Cytochrome P450



A. S. F. thanks the Tertiary Education Trust Fund for a studentship. S. P. d. V. thanks the National Service of Computational Chemistry Software UK for providing computational resource and CPU time. The EU-COST Networks for Bioinorganic Reaction Mechanisms (CM1003) and Explicit Control Over Spin states in Technology and Biochemistry (ECOSTBio, CM1305) are acknowledged for their support.

Supplementary material

775_2016_1354_MOESM1_ESM.pdf (489 kb)
Supplementary material 1 (PDF 489 kb) Tables with absolute and relative energies and group spin densities and charges as well as Cartesian coordinates of all optimized geometries and intrinsic reaction coordinate scans is available


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Copyright information

© SBIC 2016

Authors and Affiliations

  1. 1.Manchester Institute of Biotechnology, School of Chemical Engineering and Analytical ScienceThe University of ManchesterManchesterUK
  2. 2.Institut de Chimie Moleculaire et des Materiaux d’OrsayUniversité Paris Sud, Université Paris Saclay, CNRSOrsay CedexFrance

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