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 O-2 catalyzed by methan e monooxygenase (MMO) were investigated by using a hybrid density functiona l method. The reduced form of the metalloenzyme was modeled by cis-(H2O)(NH 2)Fe(eta (2)-HCOO)(2)Fe(NH2)(H2O),where the O-2 Molecule may coordinate the Fe centers from two different sides, the H2O-side and the NH2-side, leadin g to two different mechanisms, O-side and N-side pathways, respectively. Ca lculations show that both pathways proceed via similar intermediates. The e nergy profile for the reaction of O-2 coming from the O-side, however, is m ore 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 O-2 molecule would most likely approach the dinuclear iron center from thi s side rather than from the O-side. Several mixed-valence intermediates hav e 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 t o intermediate X in the analogous mechanism of Ribonucleotide Reductase, as well as an Fe-III-Fe-IV mixed-valence species prior to formation of interm ediate 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 i s the first time that a structure for intermediate P* has been proposed in the literature.