Binding free energy and extraction selectivity calculations of anisole andphenanthroline spherands

We report free energy perturbation (FEP) molecular dynamics (MD) simulation s of the relative binding free energies of three spherands and alkali metal ions (Li+, Na+, K+). The calculated free energies all favor Na+ binding an d are in reasonable agreement with experiment for two of the hosts but not the third. The third host, a mixed anisole-phenanthroline-spherand, was cal culated to be significantly selective for binding Na+ over K+ and Li+, wher eas experiments suggest little or no selectivity between K+, Na+, and Li+. Our attempts to improve the calculations by using different charge fitting schemes and by simulating the experimental conditions (addition of picrate( -) anion, simulations in chloroform) did not resolve the discrepancy. The f act that our simulations work in two cases but not the third (the third sph erand contains subunits present in the two other spherands) suggests that t here may be significant differences in the nature of the host-guest complex es in the third case.