Solvent polarization and kinetic isotope effects in nitroethane deprotonation and implications to the nitroalkane oxidase reaction

J Am Chem Soc. 2005 Nov 30;127(47):16374-5. doi: 10.1021/ja055881u.

Abstract

We have carried out a mixed molecular dynamics and centroid path integral simulation using a combined quantum mechanical and molecular mechanical (QM/MM) potential to study the anomalous Brønsted relationship between rates and equilibria for deprotonation of nitroalkanes in water, which is known as the nitroalkane anomaly. The deprotonation process is catalyzed by nitroalkane oxidase. Our results show that the difference in solvent polarization effects for the TS and products is a major factor for the differential solvent effects on rate and equilibrium of nitroalkane deprotonation. This is due to poor charge delocalization as a result of slow rehybridization compared to bond breaking. Although solvent effects do not affect significantly the computed kinetic isotope effects in comparison with the gas-phase value, there is slight solvent-induced increase in tunneling. The present results suggest that an effective means by which the transition state can be stabilized in the enzyme nitroalkane oxidase is to facilitate the Calpha rehybridization.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Computer Simulation
  • Deuterium
  • Dioxygenases / chemistry*
  • Ethane / analogs & derivatives*
  • Ethane / chemistry
  • Kinetics
  • Nitroparaffins / chemistry*
  • Protons
  • Solvents / chemistry*
  • Thermodynamics
  • Water / chemistry

Substances

  • Nitroparaffins
  • Protons
  • Solvents
  • Water
  • nitroethane
  • Deuterium
  • Dioxygenases
  • 2-nitropropane dioxygenase
  • Ethane