Binding of acetylcholine and other quaternary ammonium cations by sulfonated calixarenes. Crystal structure of a [choline-tetrasulfonated calix[4]arene] complex

Abstract

Abstract The water-soluble tetra- and hexasulfonated calix[4] and calix[6]arenes bind very strongly the neurotransmitter acetylcholine and other quaternary ammonium cations with association constants Ks up to 4×105 M−1 for NEt4 +. The high affinities for choline and acetylcholine (Ks=5×104 to 8×104 M−1) are comparable to those of the biological recognition sites. The crystal structure of the [choline-tetrasulfonated calix[4]arene] complex was determined. Two complexes A and B were observed in the asymmetric unit. In each one, the choline inserts its N-terminal inside the cavity of the receptor. The calix[4]arene adopts a single cone conformation but the choline substrate is in an extended conformation in complex A and adopts two other folded conformations in complex B (75 % –25 %). The very high association constants and the crystal structure provide important information about the nature of the binding in this biologically most relevant complex.