J. Am. Chem. Soc. http://doi.org/6j8 (2015)

Hydrogels are an intriguing class of material — despite being composed principally of water, they are solid thanks to an internal hydrophilic network. Mucus, a sticky biological hydrogel, typically consists of networks of protein–polysaccharide polymer chains, whilst soft contact lenses, which are both strong and gas permeable, are made from silicone-based hydrogels. These two examples demonstrate the breadth of both hydrogel properties and potential applications.

While much is now known about how to make hydrogels, chemists are still working to add functionality. To this end they have recently exploited the interaction between organic ligands and metal ions to generate the non-covalent crosslinking necessary to turn a solution of polymers into an aggregated gel. Extending this approach, Jonathan Nitschke and his team from the University of Cambridge and Tokyo Institute of Technology, have employed a clever technique to achieve ligand synthesis, cage formation and gelation in a single step. Previously, they succesfully employed the synthesis of supramolecular cages by metal-templated condensation of rigid bisamines and 2-formylpyridines. However in this instance, since the formylpyridines used are already pre-functionalized by substantial polyethylene glycol chains (Mn = 1000 g mol−1), the complexation into a cage upon addition of metal ions simultaneously enforces polymer aggregation, and thus drives gelation. By controlled mixing of precursor solutions within a microfluidic reactor, Nitschke and colleagues are also able to fabricate regularly sized microparticles of their cage-crosslinked hydrogels.

Credit: © 2015 ACS

Within the hydrogel, the cages retain their ability to selectively host guest-molecules with complementary steric and electronic properties. Since the imine bond formation is reversible, disassembly of the cage can be triggered by the introduction of competitive amines or aldehydes, which releases the payload and ultimately causes dissolution of the entire hydrogel. These properties may render these materials practically useful, perhaps as drug delivery vehicles. For example, a similar supramolecular cage could selectively host a therapeutic payload within a biocompatible hydrogel. The application of an external stimulus, or indeed a change in local environment (such as pH) could then trigger payload release.