Imine bond protection by supramolecular encapsulation

The imine bond (Schiff base) is ubiquitous in chemistry, biochemistry, and materials science, even though it is susceptible to hydrolysis in aqueous environments. Nature protects reactive imines by molecular encapsulation within hydrophobic protein binding pockets. This review summarizes the various synthetic supramolecular strategies that have been developed to stabilize a CN bond and protect it from hydrolysis. Early biomimetic approaches investigated self-inclusion host systems, such as deep cavitands and pillar[5]arenes, that were equipped with anchored functional groups to form stabilized imines. Other approaches used a water-soluble metallocage or cucurbit[7]uril as a host molecule to capture and protect an iminium cation or Schiff base. A recent study showed that a self-assembled capsule can sequester the two reactants (amine and carbonyl) from water and promote imine formation inside the capsule hydrophobic interior. Adding a high-affinity guest to the supramolecular complex displaces the encapsulated imine, which then hydrolyzes in the surrounding water. Future applications of this supramolecular technology are expected in prodrug delivery, responsive materials, and supramolecular catalysis.