There are many ways of looking at the rare events. I am concentrating on ways to find the minimum free energy path, that is the path that minimze the free energy while going from the reactant to the product during a chemical reaction.
In collaborations with experimentalist chemists, we use computational chemistry to study the mechanism of different organic and organometallic reactions. One of our last study consisted in comparing the Ugi and the Ugi-Smiles reactions.
We used computational chemistry to study the mechanism of the indole formation via a Heck reaction.
Computational chemistry has now become a standard tool to evaluate energy (and free energy) differences along a reaction path. However, when dealing with chemical reactions, one often relies on ab initio programs. This leads in turn to simulation costs much higher than for classical force fields. As a consequence, one must look for ways to i) generate initial path as close as possible to the unknown actual path, and ii) efficient ways to optimize this path.
Many methods already exist for the optimization of reaction path such as the Nudged Elastic Band (NEB) method and the String method. In both approaches, the reaction path is discretized as an ensemble of intermediate structures (called images) describing the transformation of the reactants into the products. The originality of our approach is to use different sets of coordinates to describe the system. This is implemented in a home made program.