Tom Ziegler^a  and Artur Michalak^a,b

 ^aDepartment of Chemistry, University of Calgary, University Drive 2500, Calgary, Alberta, Canada T2N 1N4. ^bDepartment of Theoretical Chemistry, Faculty of Chemistry, Jagiellonian University, R. Ingardena 3, 30-060 Cracow, Poland

Density functional theory (DFT) together with Car-Parrinello ab initio molecular dynamics (CP-AIMD) is a powerful tool for studies of chemical reactions. Of particular use has been the thermodynamic integration (TI) technique for direct determination of the free energy of activation in which dynamics based on CP-AIMD is performed perpendicular to the reaction coordinate. We discuss here implementations in which TI is performed along the intrinsic reaction coordinate. Further, solvation is taken into account by the COSMO continuum model. Finally, steric bulk is included in a combined quantum mechanical and molecular mechanical approach (OM/MM) where different time scales are used in the QM and MM regions.