Selectivity of 12-Crown-4 to Cations in CH3OH: A Monte Carlo Simulation Study

Abstract

Crown ethers display the ability to selectively bind specific metals cations in the presence of complex aqueous mixtures of chemically similar ions. For example, 15-crown5 binds Na and 18-crown-6 binds K selectively, although the configuration of crown depends on the solvents used. That ability is thought to be dependent on the size of the crown cavity, a balance between cation-ether and cationwater interactions, the polarity of solvent and the nature of the electron donor atoms in the ring. These characteristics have been used in the design of novel materials for such processes as isotope separations, ion transport through membrane, and transport of therapeutic doses of radiations to tumor sites. Theoretical calculations based on molecular mechanics (MM) and molecular orbital (MO) theories give structures in a vacuum, however, those results cannot be directly compared with those of experiments. In the hostguest interaction, factors in the selective extraction of any host species include the relative free energy of desolvation of the guest molecules and the free energy of organizing the host into a suitable conformation having remote substitution for binding. Because of the large number of particles forming these systems and the variety of different interactions established, molecular dynamics (MD) and Monte Carlo (MC) statistical mechanics computer simulations are wellsuited theoretical tools for understanding and predicting the physicochemical properties of those solutions at the microscopic level. Several statistical mechanical procedures have evolved for computing free energy differences. It is known that solvent effects often play an important role in determining equilibrium constants, transition states and rates of reactions, π-facial selectivity, conformations, and other quantities of chemical, chemical physics and biochemical interest. Therefore, computational chemists have focused their interests on the crown ethers as those molecules are the simplest that show enzyme-like specificity. However, few molecular dynamics (MD) and Monte Carlo (MC) statistical mechanics computer simulation studies of both the selectivity of 12-crown-4 (1,4,7,10-tetraoxacyclododecane) to univalent cations and ∆log Ks, are available. This prompted us to study the selectivity of 12-crown-4 to univalent cations and ∆log Ks using Monte Carlo simulations of statistical perturbation theory (SPT) in CH3OH. Experimental studies of the selectivity of 12-crown-4 to univalent cations in methanol and ab initio studies of 12-crown-4 with univalent cations have been reported. In this note, we present the first calculation to computing on the selectivity of 12-crown-4 to entire series of univalent cations and ∆log Ks of 12-crown-4 to entire series of univalent cations in CH3OH using a Monte Carlo simulation of SPT. We found 12-crown-4/cation complexes with the 12-crown-4 of almost Cs symmetry never found in any crystal structure of the cation complexes of 12-crown-4. Those are the reasons why this study is communicated as note. The calculated relative binding Gibbs free energies (selectivity index) of 12-crown-4 complexes and the published data of the relative free energies and Dlog Ks (the difference of stability constant of binding) obtained using by (1) shown in Scheme 1, are listed in Table 1. We have noticed that 12-crown-4 binds K more tightly than the other cation in CH3OH, i.e., the selectivity of 12-crown-4 to K is more favorable than to other cations in CH3OH. A similar trend has been observed in the study of alkali cation complexes of 18-crown-6 and its derivatives in CCl4 solutions and in the study of alkali cation complexes of 18-crown-6 in diverse solutions. Binding selectivity is often associated with the ionic radius of the cation and the size of the crown ether cavity that it will occupy. The larger mismatch is existed between the ionic radius of the cation and the size of the crown ether cavity, the smaller chance that the cation binds favorably to the crown ether cavity. 12-crown-4 has distances between diagonal oxygen atoms of 4.0 A and selectively binds K over the other cations in CH3OH where the cationic radius of K is 1.38 and the others are 0.74, 1.02, 1.49, and 1.7 A, respectively. Selectivity is apparently the result of a delicate balance of the forces that the cation experiences as the crown ether and solvent molecules compete for the cation in solution. In this study, the cations