  Free energy sampling methods allow studying the full dynamics of activated
processes. Unfortunately, the affordable accuracy of the potential describing
the energy and forces of the system is usually rather low. Here we introduce a
new method that combining metadynamics and free energy perturbation allows
calculating accurate quantum chemical free energies for chemical reactions. To
prove the effectiveness of this new approach we study the S N 2 reaction of
CH3F + Cl- -> CH3Cl + F- in vacuo and solvated by water. Comparisons are made
with harmonic transition state theory to show how this method could provide
accurate equilibrium and rate constants for complex systems.
