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

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 K-s up to 4x10(5) M(-1) for NEt(4)(+). The high affinities for choline and acetylcholine (K-s = 5x10(4) to 8x10(4) 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.