Molecular dynamics simulations of barrier crossings in the condensed phase

The isomerisation rates of a calix[4]arene in vacuo and in two solvents have been computed by means of molecular dynamics simulations (MD). In MD the equations of classical mechanics are used to calculate the motion of the reacting molecule and the surrounding solvent molecules. Thus, the intricate influence of the solvent on the reacting molecule is realistically accounted for. Unfortunately, MD simulations are computationally very demanding because of the large number of non-bonded interactions between the molecules, and the rapid internal motions of the molecules which make it necessary to calculate the interactions at femtosecond intervals. During an isomerisation reaction a molecule goes from one energetically favourable conformation to another energetically favourable conformation without breaking or forming covalent bonds. Such events are rare on the time scale of the normal dynamics of the molecule, i. e. the motion within a low energy region, since during the reaction the molecule has to pass through an energetically unfavourable region. In MD simulations of the isomerisation of a calix[4]arene in a solvent, with an experimental rate constant of about 100 s-1, a reaction event occurs roughly once every 100,000 CPU-years.