Theoretical studies on the mechanism of the methane → methanol conversion reaction catalyzed by methane monooxygenase: O-side vs N-side mechanisms

Harold Basch, Djamaladdin G. Musaev, Koichi Mogi, Keiji Morokuma

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

The hybrid density functional method B3LYP was used to study the mechanism of the methane hydroxylation reaction catalyzed by the methane monooxygenase (MMO) enzyme. The key reactive compound Q of MMO was modeled by cis-(H2O)(NH2)Fe(μ-O)22-HCOO)2 Fe(NH2)(H2O), I, where the substrate molecule may coordinate to the bridging oxygen atoms, O1 and O2, located on the H2O and NH2 sides, leading to two different mechanisms, O-side and N-side pathways, respectively. Previously we have detailed the N-side pathway (Basch, H.; Mogi, K.; Musaev, D. G.; Morokuma, K. J. Am. Chem. Soc. 1999, 121, 7249); here we discuss the O-side pathway, and compare the two. Calculations show that, like the N-side pathway, the O-side pathway of the reaction of I with CH4 proceeds via a bound-radical mechanism. It starts from the bis(μ-oxo) compound I and goes over the rate-determining transition state III_O for H abstraction from methane to . form a weak complex IV_O between the Fe(μ-O)(μ-OH)Fe moiety and a methyl radical. This bound-radical intermediate IV_O converts to the oxo-methanol complex VI_O via a low barrier at transition state V_O for the addition of the methyl radical to the μ-OH ligand. Complex VI_O easily (with about 7-8 kcal/mol barrier) eliminates the methanol molecule and produces the Fe(μ-O)Fe, VII_O, complex. During the entire process, the oxidation state of the Fe core changes from FeIV-FeIV in I to a mixed-valence FeIII-FeIV in the short-lived intermediate IV_O, and finally to FeIII-FeIII in VI_O and VII_O. A comparison of the O-side and N-side pathways shows that both include similar intermediates, transition states, and products. The rate-determining step of both pathways is the H-atom abstraction from the methane molecule, which occurs by 23.2 and 19.5 kcal/mol barrier for the O-side and N-side pathways, respectively, in the ground 9A states of the systems. Thus, the N-side pathway is intrinsically more favorable kinetically than the O-side pathway by about 4 kcal/mol. However, experimentally in the enzyme the N side is blocked by unfavorable steric hindrance and the actual reaction has to take place on the O side.

Original languageEnglish
Pages (from-to)3615-3622
Number of pages8
JournalJournal of Physical Chemistry A
Volume105
Issue number14
DOIs
Publication statusPublished - Apr 12 2001
Externally publishedYes

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Physical and Theoretical Chemistry

Cite this