Binding of acetylcholine and quaternary ammonium cations to macrocyclic and acyclic "phane" esters. Evaluation of the cation-pi primary interaction through adaptive aromatic hosts

A family of adaptive macrocyclic and acyclic "phane" esters has been design ed to systematically investigate the interaction between aromatic rings and quaternary ammonium cations in the absence of superimposed contributions, such as hydrophobic, ion-pairing, macrocyclic, and preorganization contribu tions, to quantitatively evaluate the primary force at the origin of the ca tion-pi interaction. The unprecedented association with open-chain and cycl ic nonpreorganized aromatic hosts in solutionis reported, including the rem arkable case of binding to phenylacetate ester, that allowed the direct eva luation of the interaction with a single phenyl ring. The magnitude of the cation-pi attraction has been measured in CDCl3 at T = 296 K for picrate sa lts of acetylcholine (ACh) and tetramethylammonium (TMA), the latter showin g the strongest interaction with cyclophane 1b (8.3 kT mol(-1)). Results un ambiguously confirmed that the basic driving force is a purely electrostati c attraction between the permanent charge of the cation and the aromatic ri ng. Experimental standard binding free energies suggest that interactions o f phenyl rings are additive, each contributing 2 kT mol(-1) to the overall binding energy, up to a saturation limit in the range of 8 kJ mol(-1), cons istent with tetracoordinative capabilities of quaternary ammonium cations. Cooperative effects are displayed by the ester group, itself incapable of b inding. The possible origin of the ester cooperativity is discussed.