A density functional study of possible intermediates of the reaction of dioxygen molecule with non-heme iron complexes. 1. N-side versus O-side mechanism with water-free model

Mechanistic aspects of the biological activation of O₂ catalyzed by methane monooxygenase (MMO) were investigated by using a hybrid density functional method. The reduced form of the metalloenzyme was modeled by cis-(H₂O)(NH₂)Fe(η²-HCOO)₂Fe(NH ₂)(H₂O), where the O₂ molecule may coordinate the Fe centers from two different sides, the H₂O-side and the NH₂-side, leading to two different mechanisms, O-side and N-side pathways, respectively. Calculations show that both pathways proceed via similar intermediates. The energy profile for the reaction of O₂ coming from the O-side, however, is more consistent with available experimental data than for the N-side. On the other hand, the N-side mechanism is thermodynamically more favorable. This study suggests that, if the protein backbone did not block the N-side, the O₂ molecule would most likely approach the dinuclear iron center from this side rather than from the O-side. Several mixed-valence intermediates have been found during the reaction, including an Fe^II-Fe^III mixed-valence species, P*, prior to formation of intermediate P, and a species similar to intermediate X in the analogous mechanism of Ribonucleotide Reductase, as well as an Fe^III-Fe^IV mixed-valence species prior to formation of intermediate Q. Our theoretical findings give support to the idea that electrons do not need to be transferred by pairs in the studied diiron system. This is the first time that a structure for intermediate P* has been proposed in the literature.