COMPLEXATION OF ALKALI CATIONS BY CALIX[4]CROWN IONOPHORES - CONFORMATION AND SOLVENT DEPENDENT NA+ CS+ BINDING SELECTIVITY AND EXTRACTION - MD SIMULATIONS IN THE GAS-PHASE, IN WATER AND AT THE CHLOROFORM-WATER INTERFACE/

Calix[4]arenes bridged by crown5 and crown6 moieties represent a promi sing class of ionophores for big alkali cations. We present a theoreti cal demonstration of the possible modulation of the host-guest complem entarity and recognition via the conformation of the host, and the sol vent. Molecular dynamics and free energy calculations are reported for the 1,3-dimethoxy-p-tert-butyl and the p-a-derivatives in the cone, 1 ,3-alternate, and partial cone conformations, simulated in the gas pha se and in water. In the gas phase, a decrease in binding affinity is c alculated for the three forms of the complexes, from Na+ to Cs+. Intri nsically, the largest ions prefer clearly the 1,3-alternate conformers , while Na+ prefers slightly the cone conformers. In aqueous solution, the change in free energy for mutating the Na+ calix[4]-crown6 comple x to the Cs+ complex depends markedly on the conformation of the calix arene, and is about 12 kcal/mol weaker for the 1,3-alternate than for the cone form. Taking into account the difference in desolvation energ y of the cations (30.4 kcal/mole) leads therefore to conformation depe ndent Na+/Cs+ binding selectivity. We predict that Na+ is bound select ively in the cone form, while Cs' is preferred in the 1,3-alternate fo rm, while the partial cone displays no clear Na+/Cs+ preference. The s electivity is related to the differences in precise cation location an d shielding from the solvent, as a function of the conformation of the host. We conclude that the selective binding of Cs+ by the 1,3 altern ate calix[4]-crown6 is related to solvation effects, rather than to en hanced M(+)/pi interactions with the aromatic fragments. In non-aqueou s solutions such as methanol or acetonitrile, the alternate form of ca lix[4]-crown6 is predicted to also bind Cs+ better than Na+. In dry ch loroform, the situation is expected to be close to the gas phase, i.e. Na+ preferred by all three conformers. For the smaller calix[4]-crown 5 host similar conformation dependent binding selectivity are predicte d. Finally, we report the first MD simulations on Na+ and Cs+ complexe s of the p-tert-butylcalixC6 ionophore at the water I chloroform inter face with an explicit representation of the solvents. The complexes ar e found to behave as surfactants. After 100 ps they remain close to th e interface but sit almost exclusively in the organic phase.