Chemistry and Structure of a Host–Guest Relationship: The Power of NMR and X‑ray Diffraction in Tandem

An amine/amide mixed covalent organic tetrahedral cage 1 ( H 12 ) was synthesized and characterized. The H 12 cage contains 12 amide NH groups plus four tertiary amine N groups, the latter of which are positioned in a pseudo-tetrahedral array. Crystallographic findings indicate that the tetrahedral host can adopt either a pseudo-C 3 symmetric “compressed tetrahedron” structure, or one in which there are two sets of three stacked pyridine units related by a pseudo-S4 axis. The latter conformation is ideal for encapsulating small pentameric clusters, either a water molecule or a fluoride ion surrounded by a tetrahedral array of water molecules, i.e., H2O·4H2O or F–·4H2O, as observed crystallographically. In solution, however, 19F NMR spectroscopy indicates that H 12 encapsulates fluoride ion through direct amide hydrogen bonding. By collectively combining one-dimensional 1H, 13C, and 19F with two-dimensional 1H–1H COSY, 1H–13C HSQC, and 1H–19F HETCOR NMR techniques, the solution binding mode of fluoride can be ascertained as consisting of four sets of independent structural subunits with C 3 symmetry. A complex deuterium exchange process for the fluoride complex can also be unraveled by multiple NMR techniques.