that the transition state model is largely OK. The observation that the predicted magnitudes of the KIE are slightly larger than measured may also be associated with the use of theory based on a harmonic oscillator model, whereas the observed values are associated with anharmonic vibrational effects. 8. Substituent effects. Three substituents at the extremes of electron donation and withdrawal were selected to probe how the kinetic isotope was affected, R = NO2, NMe2 and CF3 (Scheme 1 and Table ). For R=CF3, 56 the transition state geometry (Figure ) shows a more compact and more symmetrical and linear hydrogen-transfer centre compared to R=H (Figure ). These factors combine to increase the predicted value KIE195 for R=CF3 to 3.85, compared to 2.51 at the same level for R=H. The substituents R=NO2 further increase this trend. An even larger effect is seen for R=NMe2 (Figure ), 57 with the S-O bond now largely broken at the transition state and the reaction comprising an almost pure and more symmetrical hydrogen transfer with the angle at the transferring centre now approaching linearity. These properties all combine to further increase the predicted value KIE195 for R=NMe2 to 10.1, of which a factor of 1.46 is now due to larger tunnelling contributions associated with the larger value of ni 765 cm -1 . Whilst these specific substituents may not be synthetically feasible, we have at least established a consistent method for predicting isotope effects for new substituents located in any position in the substrates and hence of designing variations on the Swern oxidation that could sustain larger deuterium kinetic isotope effects.