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-S(4) 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., H(2)O·4H(2)O or F(-)·4H(2)O, as observed crystallographically. In solution, however, (19)F NMR spectroscopy indicates that H(12) encapsulates fluoride ion through direct amide hydrogen bonding. By collectively combining one-dimensional (1)H, (13)C, and (19)F with two-dimensional (1)H-(1)H COSY, (1)H-(13)C HSQC, and (1)H-(19)F 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.