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Mechanical calculations for methyl transfer in solution

13 Nov 2008 - Ian Williams and colleagues at the University of Bath, UK, have demonstrated that kinetic isotope effects (KIEs) for a prototypical S­N­2 methyl transfer in solution, and in an enzyme active site, show significant variations in magnitude owing to thermally-induced structural fluctuations.
 
Williams’ team have shown that thermal fluctuations must be taken into account to properly reproduce experimental KIE values, as different families of reactant-state conformers yield different KIE values.
 
Using hybrid quantum-mechanics/molecular mechanics (QM/MM) calculations this concept discloses that an ensemble-averaging of KIE is necessary to produce data featuring quantitative experimental accuracy.
 
‘These results represent a proof of concept; their quantitative accuracy may be improved by more expensive simulations using higher-level quantum-chemical methodologies in the future,’ said Williams.
 
Original publication: Ian Williams et al., Chem. Commun., 2008.