MECHANISM AND THERMODYNAMICS OF ION SELECTIVITY IN AQUEOUS-SOLUTIONS OF 18-CROWN-6 ETHER - A MOLECULAR-DYNAMICS STUDY

We have performed extensive classical molecular dynamics simulations to examine the mechanism and thermodynamics for ion selectivity of 18-crown-6 ether in aqueous solutions. We have computed the free energy profiles or potentials of mean force and the corresponding binding free energies for M(+):18-crown-6 (M(+) = K+, Na+, Rb+, Cs+) complexation in water. The long-range interactions are computed via the Ewald summation method, and counterion effects are considered. To the best of our knowledge, the present work is the first to employ the potential of mean force approach to the evaluation of crown ether selectivity in an aqueous solution. The resultant potentials of mean force indicate that minima free energy surfaces for K+ and Na+ are located at the crown ether center-of-mass. A well-defined second minimum is also observed in the potential of mean force of the Na+:18-crown-6 complex in water. It appears that Kf is selected over Nai because of the greater free energy penalty associated with displacing water molecules from Na+ as it approaches the crown ether. This leads to a substantial increase in the activation free energy and a decrease in the corresponding binding free energy for Na+:18-crown-6 complexation as compared to K+:18-crown-6. The selection of K+ over Rb+ and Cs+ is due to the size of the cation relative to that of the crown ether cavity. Although the calculated binding free energies underestimate the experimental measurements, they correctly reproduce the experimental sequence trends K+ > Rb+ > Cs+ > Na+. The present work not only reproduces the experimental observations but also provides a detailed physical description of the mechanism for ion selectivity in macrocyclic crown ethers.