DRAMATIC SOLVENT EFFECT ON THE LIGAND WRAPPING AROUND A COMPLEXED CATION - A MOLECULAR-DYNAMICS STUDY OF P-TERT-BUTYLCALIX[4]ARENE TETRAMIDE AND ITS COMPLEXES WITH ALKALI CATIONS AND EU3+ IN ACETONITRILE

A series of molecular dynamics (MD) simulations have been performed on tert-butylcalix[4]arene tetramide ligand L and its complexes with cations Li+ to Cs+ and Eu3+ in acetonitrile solution in order to elucidate the structural basis of complexation of cations by an ionophore possessing a highly flexible nonpreorganized pseudocavity. Comparison of its dynamic behavior in acetonitrile and in water demonstrates the dramatic solvent effect on the extent of ligand wrapping around the complexed ions. The binding mode of cation complexes in acetonitrile differs significantly from the picture provided by the solid-state structure of LK+ complex and from structures simulated in gas phase and in water. In water, significant hydration of C=O putative binding sites leads to open-type conformers where carbonyls are poorly involved in the cation binding. In acetonitrile, carbonyls adopt more converging orientations and the pseudocavity at lower rim provides better cation shielding from the solvent. Questions pertaining to preorganization and the filling of the cone by solvent molecules are analyzed. Finally, the question of binding selectivity in a nonaqueous solvent is addressed by free energy perturbation calculations, which lead to correct trends in complexation selectivity of the calixarene L for alkali cations (Li+ > Na+ > K+ > Rb+ > Cs+).