Alkali metal cation selectivity of [1(7)]ketonand in methanol: Free energyperturbation and molecular dynamics simulation studies

Free energy perturbation and molecular dynamics simulations were carried ou t to investigate the relative binding affinities of [1(7)]ketonand (1) towa rd alkali metal cations in methanol. The binding affinities of 1 toward the alkali metal cations were calculated to be in the order Li+ > Na+ > K+ > R b+ > Cs+, whereas our recent theoretically predicted and experimentally obs erved binding affinities for [1(8)]starand (2) were in the order K+ > Rb+ > Cs+ > Na+ > Li+. The extremely different affinities of 1 and 2 toward smal ler cations, Li+ and Na+, were explained in terms of the differences in the ir ability to change the conformation to accommodate cations of different s izes. The carbonyl groups constituting the central cavity of 1 can reorgani ze to form a cavity with the optimal M+-O distance, even for the smallest L i+, without imposing serious strain on 1. The highest affinity of 1 for Li was predominantly due to the highest Coulombic attraction between the smal lest Li+ and the carbonyl oxygens of 1.