Synthesis of the first water-soluble hemicryptophane host: selective recognition of choline in aqueous medium.

The first water-soluble hemicryptophane cage compound, 4, was synthesized in seven steps from commercially available products, and its complexation properties were studied. NMR and ITC experiments indicate that 4 is an efficient receptor for choline in water (ΔG° = -5.2 kcal mol(-1)). High substrate selectivity was achieved since no complexation was observed for its closely related substrates: glycine betaine and betaine aldehyde. Density functional theory calculations were performed to analyze the interactions that are involved in the formation of the inclusion complex.