Pathways for Arene Oxidation in Non-Heme Diiron Enzymes: Lessons from Computational Studies on Benzoyl Coenzyme A Epoxidase

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Oxygenation of aromatic rings using O2 is catalyzed by several non-heme carboxylate-bridged diiron enzymes. In order to provide a general mechanistic description for these reactions, computational studies were carried out at the ONIOM(B3LYP/BP86/Amber) level on the non-heme diiron enzyme benzoyl coenzyme A epoxidase, BoxB. The calculations revealed four possible pathways for attacking the aromatic ring: (a) electrophilic (2e-) attack by a bis(μ-oxo)-diiron(IV) species (Q pathway); (b) electrophilic (2e-) attack via the σ∗ orbital of a μ-η22-peroxo-diiron(III) intermediate (Pσ∗ pathway); (c) radical (1e-) attack via the π∗-orbital of a superoxo-diiron(II,III) species (Pπ∗ pathway); (d) radical (1e-) attack of a partially quenched bis(μ-oxo)-diiron(IV) intermediate (Q′ pathway). The results allowed earlier work of de Visser on olefin epoxidation by diiron complexes and QM-cluster studies of Liao and Siegbahn on BoxB to be put into a broader perspective. Parallels with epoxidation using organic peracids were also examined. Specifically for the BoxB enzyme, the Q pathway was found to be the most preferred, but the corresponding bis(μ-oxo)-diiron(IV) species is significantly destabilized and not expected to be directly observable. Epoxidation via the Pσ∗ pathway represents an energetically somewhat higher lying alternative; possible strategies for experimental discrimination are discussed. The selectivity toward epoxidation is shown to stem from a combination of inherent electronic properties of the thioacyl substituent and enzymatic constraints. Possible implications of the results for toluene monooxygenases are considered as well.

Original languageEnglish
Pages (from-to)14623-14638
Number of pages16
JournalJournal of the American Chemical Society
Issue number44
Publication statusPublished - Nov 9 2016

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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