Hydroxylation mechanism of methane and its derivatives over designed methane monooxygenase model with peroxo dizinc core

Org Biomol Chem. 2012 May 21;10(19):3924-31. doi: 10.1039/c2ob25163a. Epub 2012 Apr 11.

Abstract

The peroxo dizinc Zn(2)O(2) complex Q coordinated by imidazole and carboxylate groups for each Zn center has been designed to model the hydroxylase component of methane monooxygenase (MMO) enzyme, on the basis of the experimentally available structure information of enzyme with divalent zinc ion and the MMO with Fe(2)O(2) core. The reaction mechanism for the hydroxylation of methane and its derivatives catalyzed by Q has been investigated at the B3LYP*/cc-pVTZ, Lanl2tz level in protein solution environment. These hydroxylation reactions proceed via a radical-rebound mechanism, with the rate-determining step of the C-H bond cleavage. This radical-rebound reaction mechanism is analogous to the experimentally available MMOs with diamond Fe(2)O(2) core accompanied by a coordinate number of six for the hydroxylation of methane. The rate constants for the hydroxylation of substrates catalyzed by Q increase along CH(4) < CH(3)F < CH(3)CN ≈ CH(3)NO(2) < CH(3)CH(3). Both the activation strain ΔE(≠)(strain) and the stabilizing interaction ΔE(≠)(int) jointly affect the activation energy ΔE(≠). For the C-H cleavage of substrate CH(3)X, with the decrease of steric shielding for the substituted CH(3)X (X = F > H > CH(3) > NO(2) > CN) attacking the O center in Q, the activation strain ΔE(≠)(strain) decreases, whereas the stabilizing interaction ΔE(≠)(int) increases. It is predicted that the MMO with peroxo dizinc Zn(2)O(2) core should be a promising catalyst for the hydroxylation of methane and its derivatives.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biocatalysis
  • Enzyme Activation
  • Hydroxylation
  • Methane / analogs & derivatives
  • Methane / chemistry*
  • Methane / metabolism
  • Models, Molecular
  • Molecular Structure
  • Oxygenases / chemistry*
  • Oxygenases / metabolism
  • Substrate Specificity
  • Zinc / chemistry*

Substances

  • Oxygenases
  • methane monooxygenase
  • Zinc
  • Methane