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 (H12) was
synthesized and characterized. The H12 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-C3 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 H12 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 C3 symmetry. A complex deuterium
exchange process for the fluoride complex can also be unraveled by
multiple NMR techniques.