Molecular recognition by wall-assembling-type nanocavity in aqueous media

Steroid cyclophanes, each having a macrocyclic ring attached to four bile acid moieties via chiral lysine connectors, were synthesized, and the binding of the 2-naphthylphenylketone (guest) to the steroid cyclophanes in water was investigated. The circular dichroism spectra of the steroid cyclophane with cholic acid and L-lysine were significantly affected by the binding of the guest, and the induced circular dichroism based on the absorption of the achiral guest was also observed. The binding of the guest to the steroid cyclophane with cholic acids and D-lysines induced changes in the circular dichroism spectra with the opposite sign of the molecular ellipticities. An induced circular dichroism spectral change was not observed upon binding of the guest to the analogous host without OH sites. These results strongly suggest that the guest is conformationally fixed through hydrogen bonding between the carbonyl group of the guest and the steroidal hydroxyl group of the host. The assembly of only four steroid residues on the macrocyclic ring probably provided a hydrophobic nanocavity for hydrogen bonding.