Binding of Acetylcholine and Quaternary Ammonium Cations to Macrocyclic and Acyclic “Phane” Esters. Evaluation of the Cation−π Primary Interaction through Adaptive Aromatic Hosts

Citations Over TimeTop 10% of 1998 papers

Abstract

A family of adaptive macrocyclic and acyclic “phane” esters has been designed 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 contributions, to quantitatively evaluate the primary force at the origin of the cation−π interaction. The unprecedented association with open-chain and cyclic nonpreorganized aromatic hosts in solution is reported, including the remarkable case of binding to phenylacetate ester, that allowed the direct evaluation of the interaction with a single phenyl ring. The magnitude of the cation−π attraction has been measured in CDCl3 at T = 296 K for picrate salts of acetylcholine (ACh) and tetramethylammonium (TMA), the latter showing the strongest interaction with cyclophane 1b (8.3 kJ mol-1). Results unambiguously confirmed that the basic driving force is a purely electrostatic attraction between the permanent charge of the cation and the aromatic ring. Experimental standard binding free energies suggest that interactions of phenyl rings are additive, each contributing 2 kJ mol-1 to the overall binding energy, up to a saturation limit in the range of 8 kJ mol-1, consistent with tetracoordinative capabilities of quaternary ammonium cations. Cooperative effects are displayed by the ester group, itself incapable of binding. The possible origin of the ester cooperativity is discussed.

Related Papers

• → SYNTHESIS OF ACETYLCHOLINE IN DIFFERENT COMPARTMENTS OF BRAIN NERVE TERMINALS IN VIVO AS STUDIED BY THE INCORPORATION OF CHOLINE FROM PLASMA AND THE EFFECT OF PENTOBARBITAL ON THIS PROCESS(1973)55 cited
• → Quinacrine and 2-(4-phenylpiperidino)cyclohexanol (AH5183) inhibit acetylcholine release and synthesis in rat brain slices.(1986)42 cited
• → STUDIES OF THE EFFECTS OF AGENTS WHICH ALTER CALCIUM METABOLISM ON ACETYLCHOLINE TURNOVER IN THE RAT DIAPHRAGM PREPARATION(1981)20 cited
• → Spontaneous and potassium-induced release of acetylcholine from mouse forebrain minces(1981)20 cited
• → Inability of Parallel Bio-assay to recognize Acetylcholine in Mixtures of Substances with Acetylcholine-like Activity(1965)4 cited