Molecular dynamics study of ion capture from water by a model ionophore, tetraprotonated cryptand SC24.

A molecular dynamics study of chloride capture from water by the tetraprotonated cryptand SC24 is presented. The system under study consisted of a cryptand molecule, chloride ion, and 319 water molecules. Calculations were performed for 19 distances between the cryptand and the chloride. For each distance a trajectory of at least 60 ps was obtained. Two anion binding sites of comparable energy were found. The chloride can bind either inside the cryptand cavity or more loosely outside of the ligand. The binding sites are separated by an energy barrier of 20 kcal/mol. Chloride movement toward the cryptand is accompanied by stepwise dehydration of the anion. The energy loss due to this dehydration is offset by the electrostatic attraction between the anion and the ligand and by an increase in favorable water-water interactions. The most striking feature of chloride capture is a rapid cooperative change in the conformation of the cryptand when the Cl- starts to enter the ligand and just as it encounters the energy barrier. The conformational transition is associated with a shift of three N-H bonds from the pure endo orientation, so that they point toward the chloride. The shift provides electrostatic stabilization, which compensates for the loss of the remaining three water molecules from the hydration shell of the anion. The N-H bonds remain directed toward the anion during its further movement into the ligand and guide chloride into a stable position inside the cryptand cavity. The flexibility of the receptor, the stepwise dehydration of an ionic substrate, and the characteristic balance between different energy components in the system all may be features of ion binding common to a wide range of abiotic and biological ionophores.

A molecular dynamics study of chloride binding by the cryptand SC24.

The capture of chloride from water by the tetraprotonated form of the spherical macrotricyclic molecule SC24 was studied using molecular dynamics simulation methods. This model ionophore represents a broad class of molecules which remove ions from water. Two binding sites for the chloride were found, one inside and one outside the ligand. These sites are separated by a potential energy barrier of approximately 20 kcal mol-1. The major contribution to this barrier comes from dehydration of the chloride. The large, unfavorable dehydration effect is compensated for by an increase in electrostatic attraction between the oppositely charged chloride and cryptand, and by energetically favorable rearrangements of water structure. Additional assistance in crossing the barrier and completing the dehydration of the ion is provided by the shift of three positively charged hydrogen atoms of the cryptand towards the chloride. This structural rigidity is partially responsible for its selectivity.