Importance of the proximity of solvation: molecular dynamics and free energy perturbation studies of [16]starand and its model with various alkali metal ions

Abstract

Strong affinity and high selectivity are good characteristics of a host in host–guest chemistry. Because [16]starand has only one conformation, it should serve as a good probe to study fine structure of solvation. We investigated the complexation behavior of [16]starand and its model with various alkali metal ions using free energy perturbation and molecular dynamics methods. The results from gas phase simulations show that the binding energy difference decreases as the radius of metal ion increases, with only a small disparity between the binding energy difference and binding free energy difference. This small entropy effect in the gas phase may be due to the structural rigidity of [16]starand and its model system. When the complexes lie immersed in water, the order of binding free energies reverses, i.e. the binding energy increases as the radius of alkali metal ion increases. This reversal of order should be from solvent effect. To investigate why complexations with larger metal ions are favored in water, we performed radial distribution function (RDF) analyses from alkali ions to water oxygens. Water coordination numbers for the free solvated ions (NW) and for those in complexes (NC) in aqueous solution were obtained from the RDF data. One might rationally anticipate that the relative free energies would correlate well with the ratio of these coordination numbers (NC/NW), but our findings suggest no direct relationship exists. Interestingly, however, the order of relative binding energies does relate to the solvation ratio within a constant radius very near to the ions. These results demonstrate that the proximity of solvation is an important factor to decide the relative binding free energies.