title: Computational simulation of the lifetime of the methoxymethyl cation in water. A simple model for a glycosyl cation: when is an intermediate an intermediate?
abstract: A two-dimensional free-energy surface is constructed for transfer of the methoxymethyl cation between two water molecules. These atoms are treated quantum mechanically within a box of >1000 classical solvent water molecules, and the molecular dynamics of the whole system is considered at 300 K. This provides a simple model for glycosyl transfer in water. The best surface obtained (MPWB1K/6-31+G(d,p) corrected AM1/TIP3P) contains a shallow free-energy well corresponding to an oxacarbenium ion intermediate in a stepwise mechanism. Molecular dynamics analysis at three temperatures leads to a classical estimate of the lifetime of the methoxymethyl cation in water; when quantum corrections for vibrational zero-point energy are included, the lifetime is estimated to be 1 ps. This result is in complete agreement with the best experimental estimate and suggests that computational simulation is a reliable tool for elucidation of glycosyl-transfer mechanisms in enzymes and whether these involve glycosyl cations as intermediates.
authors.affiliation: Department of Chemistry, University of Bath, Bath, BA2 7AY, UK.
authors.forename: J Javier
authors.initials: JJ
authors.lastname: Ruiz Pernía
authors.forename: Iñaki
authors.initials: I
authors.lastname: Tuñón
authors.forename: Ian H
authors.initials: IH
authors.lastname: Williams
mesh_terms: D002412:Cations / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011789:Quantum Theory; D013696:Temperature; D014867:Water / Q000737:chemistry*
chemical_list: D002412:Cations; D014867:Water