MOLECULAR-DYNAMICS AND FREE-ENERGY PERTURBATION STUDY OF SPHERAND COMPLEXATION WITH METAL-IONS EMPLOYING ADDITIVE AND NONADDITIVE FORCE-FIELDS

Molecular dynamics and free energy perturbation have been applied to s tudy the complexation and the selectivity of a host molecule hexaaniso le spherand (1) with its metal ion ligands, Two different potential fu nction force fields were tested: a two-body interactive potential with the TIP3P water model and a recently derived polarizable and three-bo dy interactive potential including a polarizable water model. Our resu lts show that the two-body additive potential is able to provide usefu l information on the relative binding affinities of alkali metal ions, although for the Na+ --> Li+ case the agreement with experiment is on ly qualitative. The relative binding free energy of Li+ and Na with th e hexaanisole spherand is calculated to be -2.7 kcal/mol, compared to the experimental value of < -3.8 kcal/mol. The agreement improved when the mole sophisticated polarizable and three-body interactive potenti al force field was employed, resulting in a relative binding free ener gy of Li+ and Na+ of -3.7 kcal/mol. We have also tested different elec trostatic charge fitting protocols and models, and the results showed that the choice of protocol is of critical importance for obtaining qu antitative agreement with experiment.