Pathways for Arene Oxidation in Non-Heme Diiron Enzymes: Lessons from Computational Studies on Benzoyl Coenzyme A Epoxidase.
Oxygenation of aromatic rings using O2is 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-η2:η2-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.
Institute of Organic Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences , Magyar Tudósok körútja 2, 1117 Budapest, Hungary.
Tibor András
TA
Rokob
D000214:Acyl Coenzyme A / Q000737:chemistry*; D000475:Alkenes / Q000737:chemistry*; D003198:Computer Simulation; D056831:Coordination Complexes; D004852:Epoxy Compounds / Q000737:chemistry; D007501:Iron / Q000737:chemistry*; D008958:Models, Molecular; D019159:Nonheme Iron Proteins / Q000737:chemistry*; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000737:chemistry*; D010100:Oxygen / Q000737:chemistry
D000214:Acyl Coenzyme A; D000475:Alkenes; D056831:Coordination Complexes; D004852:Epoxy Compounds; D019159:Nonheme Iron Proteins; C037817:benzoyl-coenzyme A; D007501:Iron; D010088:Oxidoreductases; C023111:epoxidase; D010100:Oxygen