Conformational mobility and efficiency in supramolecular catalysis: a computational approach to evaluate the performances of enzyme mimics

In the present study, we apply a computational approach, based on DFT calculations and molecular dynamics simulations, to investigate the catalytic behavior of four supramolecular catalysts active in the cleavage of phosphodiesters. The QM data indicate the operation of a synchronous associative mechanism with limited differences in the structures and energies of the transition states. The comparison with the experimental data, expressed in terms of effective molarity (EM), suggests that the difference in catalytic performance are not ascribable to a difference in the enthalpy of activation. On the other hand, the analysis of the Molecular Dynamics trajectories clearly indicates the conformational mobility, and therefore the conformational entropy, to be at the origin of the superior catalytic efficiency of the catalysts based on a more preorganized structure. Essentially, the combined method presented here provides, at a limited computational cost, a tool that is simple, general, and potentially suited for a large variety of catalytic systems to rationalize their performances and to predict those of enzyme mimics to be synthesized in a rational design process.