Enantioselective Recognition of Neutral Molecules in Water by a Pair of Chiral Biomimetic Macrocyclic Receptors

Enantioselective recognition in water remains an ongoing challenge in supramolecular chemistry but is routine in nature. Herein, we report the first enantiopure pair of biomimetic macrocyclic receptors with hydrogen bonding donors in their deep hydrophobic cavities. The chiral naphthotubes can be efficiently synthesized through a chirality-directed macrocyclization strategy and are able to discriminate the enantiomers of neutral chiral molecules in water. Density functional theory calculations reveal that the three-point contact model effectively explains their enantioselectivity. The differential noncovalent interactions inside the hydrophobic cavity are responsible for the enantioselective recognition. Moreover, these chiral naphthotubes are both fluorescent and circular dichroism (CD)-active. In CD spectroscopy, they have been demonstrated to have the ability to detect nonchromophoric, achiral molecules in water. And, the use of fluorescence spectroscopy has aided in the determination of the enantiomeric excess (ee) values of chiral molecules. The results and conclusions obtained with these chiral biomimetic receptors can be used to better understand enantioselective recognition in biological systems.