Halide anion recognition in water by a hexaprotonated octaaza-cryptand: a molecular dynamics investigation

Based on molecular dynamics simulations, we describe the F- versus Cl- complexation by an hexaprotonated cryptand L6+ in aqueous solution, in order to elucidate their structures, solvation properties and the status of external halide counterions. In water, F- and Cl- simulated inclusive complexes adopt a structure somewhat different from the solid state structure of the F- complex: The anion binding involves two diammonium bridges only, and the accompanying counterions are dissociated from the +5 charged complex. A remarkable result is obtained for the dissociated L6+,3F- ,3Cl- system, where spontaneous complexation of F- (the anion which forms the most stable complex with L6+) takes place during the dynamics. The resulting complex is of facial type; this suggests that the equilibrium involves multiple binding modes and structures in aqueous solution. The question of F-/Cl- binding selectivity is investigated by free energy perturbations simulations which nicely reproduce the spectacular preference for F- over Cl-. Two different methodologies used for the treatment of electrostatics (standard versus Ewald calculations) yield similar conclusions.