Relative binding affinities of alkali metal cations to [1₈]starand in methanol: Computational and experimental studies

The binding affinity and selectivity of a new ionophore, [1₈]starand (1), toward alkali metal cations in methanol were examined through NMR titration experiments and free energy perturbation (FEP) and molecular dynamics simulations. The preference was determined to be K⁺ > Rb⁺ > Cs⁺ > Na⁺ >> Li⁺ in both FEP simulations and NMR experiments. The FEP simulation results were able to predict the relative binding free energies with errors less than 0.13 kcal/mol, except for the case between Li⁺ and Na⁺. The cation selectivity was rationalized by analyzing the radial distribution functions of the M-O and M-C distances of free metal cations in methanol and those of metalionophore complexes in methanol.