Influence of Equatorial CH⋅⋅⋅O Interactions on Secondary Kinetic Isotope Effects for Methyl Transfer. Issue 9 (28th January 2016)

• Record Type: Journal Article
• Authors: Wilson, Philippe B.; Williams, Ian H.
• Is Part Of: Angewandte Chemie international edition. Volume 55:Issue 9(2016)
• Page Start: 3192
• Page End: 3195
• Publication Date: 2016-01-28
• Subjects: computational chemistry -- enzyme catalysis -- hydrogen bonds -- isotope effects -- methyl transfer; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201511708
• Languages: English
• ISSNs: 1433-7851

Abstract

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. Abstract : Behavior in confinement : k (CH3 )/ k (CT3 ) for methyl transfer in a constrained cage of water molecules was found to be sensitive to CH⋅⋅⋅O hydrogen‐bonding interactions: It increased by 3 % as the equatorial distance r eq decreased from 3.5 to 3.0 Å for a constant axial distance r ax =2.0 Å (see graph), thus suggesting that factors other than axial compression may contribute to isotope‐effect variations for methyltransferase and its mutant structures.