Influence of Equatorial CH⋅⋅⋅O Interactions on Secondary Kinetic Isotope Effects for Methyl Transfer

Date

2016-01-28

Advisors

Journal Title

Journal ISSN

ISSN

Volume Title

Publisher

Wiley

Type

Article

Peer reviewed

Yes

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.

Description

This is an Open Access article

Keywords

Isotope Effect, Methyl Cation, Post Hartree-Fock, Density Functional Theory, Scaling Factor

Citation

Wilson, P.B. and Williams, I.H. (2016) Influence of Equatorial CH⋅⋅⋅O Interactions on Secondary Kinetic Isotope Effects for Methyl Transfer. Angewandte Chemie. 128 (9), pp. 3244-3247

Rights

Research Institute

Leicester Institute for Pharmaceutical Innovation - From Molecules to Practice (LIPI)