Controlling Swing Rates in Macrocyclic Molecular Mortise Hinges

Hinge motion is observed in macrocyclic, mortise-type molecular hinges using variable temperature NMR spectroscopy. The data is consistent with dynamic hinging from a folded-to-extended-to-folded enantiomeric states. Crystallographic and solution structures of the folded states are reported. Chemical shift predictions derived from crystallographic data corroborate fully revolute hinge motion. The rate of hinging is affected by steric congestion at the hinge axis.  Macrocycles containing glycine, 1, hinge faster than those comprising aminoisobutyric acid, 2. The free energies of activation, ΔG‡, for 1 and 2 were determined to be 13.3  ±  0.3 kcal/mol and 16.3 ± 0.3 kcal/mol, respectively. This barrier is largely independent of solvent across those surveyed (CD3OD, CD3CN, DMSO-d6, pyridine-d5, D2O). Experiment and computation predict energy barriers that are consistent with disruption of an intramolecular network of hydrogen bonds. DFT calculations reveal pathways for hinge motion.