Virtual transition states: making sense of multiple transition states in parallel and series

The apparent Gibbs energies of activation for chemical reactions that involve multiple paths in parallel and/or multiple steps in series may involve several transition states (TSs) lying close in energy. The virtual TS is a weighted average of these contributing real TSs, and the weighting factors are easily obtained from the Gibbs energies of these TSs relative to a common reactant state. Examples from organic reaction mechanisms are used to illustrate the concept and its implications for the interpretation of features of complex Hammett plots and of kinetic isotope effects (KIEs). The concept allows for a considerable simplification of the treatment of KIEs for enzymic reactions, and holds promise for the application of modern methods of computational simulation to assist in the interpretation of experimental kinetic investigations of complex mechanisms.