Anion allosteric effect in the recognition of tetramethylammonium salts bycalix[4]arene cone conformers

Rigid calix [4] arene cone conformers, which are efficient receptors for qu aternary ammonium salts, are usually obtained through the functionalization of their lower rim with suitable groups. Using flexible cone conformer of calix[4]arene, bearing four 4-hydroxybenzyl groups as cooperative and rigid ifying structural elements at the upper rim of the calix, which act as anio n binding groups, a new heteroditopic cavitand, 7, was synthesized. Whereas the tetramethoxy derivative 8 does not show any complexing ability, its te trahydroxy analogue 7 recognizes tetramethylammonium salts with high effici ency. The binding abilities of this new receptor toward a series of tetrame thylammonium salts (tosylate, chloride, acetate, trifluoroacetate, and picr ate) have been investigated in CDCl3 solution and compared to the monotopic and rigidified, through the lower rim, cone biscrown-3-calix [4] arene 9. The results obtained confirmed that in CDCl3 ion pairing strongly affects b inding. In particular, the rigid monotopic receptor 9 experiences good effi ciency toward tetramethylammonium salts having anions with low ion-pairing ability such as trifluoroacetate or picrate. On the contrary, for the new h eteroditopic cavitand 7, a reverse order of efficiency was found. In the la tter case a different complexation mode was hypothesized in which the tetra methylammonium cation is deeply entrapped into the host cavity and its coun teranion participates to the recognition process by coordination via hydrog en bonding by the four OH groups. To further support the role of the anion in the recognition process, a "dual host" approach, employing 7 or 9 in the presence of a specific receptor for chloride anion (10), was utilized. Mol ecular modeling studies confirmed that in the complexes formed by 7 and TMA salts the counteranion is involved in hydrogen bonding with the host OH gr oups and that the guests are bound as ligand-separated ion pairs.