Influence of Equatorial CHO Interactions on Secondary Kinetic Isotope Effects for Methyl Transfer

摘要

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 CO distances: a decrease of 0.5 angstrom results in a 3% increase at 298K. Kinetic isotope effects in AdoMet-dependent methyltransferases may be m perpendicular to odulated by CHO 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.