requires that both activation and reaction free energies are available, either from experiments or quantum mechanical calculations. The activation free energy for the uncatalyzed transformation of chorismate to prephenate has previously been experimentally determined to 24.5 kcal/mol but the reaction free energy, ∆G0, is not available. Thus, to obtain a reference for ∆G0 we carried out DFT calculations for the unimolecular conversion of chorismate to prephenate in water (Figure ). To stabilize the charged carboxylic acid groups on the chorismate, 5 explicit water molecules were included. The B3LYP/6-311G+(2d,2p) model with CPCM solvation correction yields a barrier of 24.4 kcal/mol, which is in excellent agreement with the corresponding experimental result. Moreover, the reaction free energy was calculated to be -13.2 kcal/mol, which is very close to the experimentally observed reaction enthalpy, ∆H0 = -13.3 kcal/mol, that was also previously used by Warshel et al. to estimate ∆G0 for this reaction. Even though the CPCM model is often considered one of the most successful solvation models, the more recent SMD model developed by Truhlar et al. is also popular, perhaps more commonly in combination with the Minnesota functionals developed by the same group.