Acceleration of amide bond rotation by encapsulation in the hydrophobic interior of a water-soluble supramolecular assembly

Article abstract of DOI:10.1021/jo800991g

(Chemical Equation Presented) The hydrophobic interior cavity of a self-assembled supramolecular assembly exploits the hydrophobic effect for the encapsulation of tertiary amides. Variable-temperature ¹H NMR experiments reveal that the free energy barrier for rotation around the C-N amide bond is lowered by up to 3.6 kcal/mol upon encapsulation. The hydrophobic cavity of the assembly is able to stabilize the less polar transition state of the amide rotation process. Carbon-13 labeling studies showed that the ¹³C NMR chemical shift of the carbonyl resonance increases with temperature for the encapsulated amides, which suggests that the assembly is able to favor a twisted form of the amide.