title: Influence of Equatorial CH⋅⋅⋅O Interactions on Secondary Kinetic Isotope Effects for Methyl Transfer.
abstract: DFT calculations for methyl cation complexed within a constrained cage of water molecules permit the controlled manipulation of the "axial" donor/acceptor distance and the "equatorial" distance to hydrogen-bond acceptors. The kinetic isotope effect k(CH3)/k(CT3) for methyl transfer within a cage with a short axial distance becomes less inverse for shorter equatorial C⋅⋅⋅O distances: a decrease of 0.5 Å results in a 3 % increase at 298 K. Kinetic isotope effects in AdoMet-dependent methyltransferases may be m∧odulated by CH⋅⋅⋅O hydrogen bonding, and factors other than axial compression may contribute, at least partially, to recently reported isotope-effect variations for catechol-O-methyltransferase and its mutant structures.
authors.affiliation: Department of Chemistry, University of Bath, Bath, BA2 7AY, UK.
authors.forename: Philippe B
authors.identifier: http://orcid.org/0000-0003-0207-2246
authors.initials: PB
authors.lastname: Wilson
authors.affiliation: Department of Chemistry, University of Bath, Bath, BA2 7AY, UK. I.H.Williams@bath.ac.uk.
authors.forename: Ian H
authors.identifier: http://orcid.org/0000-0001-9264-0221
authors.initials: IH
authors.lastname: Williams
keywords: computational chemistry; enzyme catalysis; hydrogen bonds; isotope effects; methyl transfer
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