Molecular submarines

The cage-like structure means that these large molecules can trap 'guest' atoms or molecules within themselves. Moreover, chemists can design specific cages for trapping specific guests. This means they can be used as sensors – for example to detect an environmental pollutant, or for transport – for example in drug delivery. They can also be used as catalysts in chemical reactions – holding the starting materials in the right positions to react.

Chemists have designed and synthesised a whole variety of molecular cages, but one big drawback has limited their usefulness. For many applications, the cages need to be soluble in water and other media. For example, to detect or trap pollutants in water, the cages need to first dissolve in the water. Similarly, if a cage is not soluble, it can’t be injected into the bloodstream or used by the body’s cells. Furthermore, once immersed in the water or other medium, they have to be stable enough not to disintegrate.

Many existing cages are either insoluble in water or unstable in solution or both. Jonathan Nitschke and his group at the University of Cambridge have designed a solution to this problem. They found that it was important to carefully select the metal cation, and that a nickel cation led to a much more stable cage than other popular choices such as cobalt, zinc and cadmium. They also used sulfate counterions to render the cages soluble in water.

The final touch is that the starting materials – the ligands – don’t themselves have to be water soluble. By following the method outlined in the paper it is possible to assemble a soluble molecular cage from insoluble starting materials.

The result is a tiny submarine – water soluble and waterproof – capable of detecting, capturing and transporting tiny ‘passenger’ molecules and atoms.

"Our study represents a significant step forward in the design of abiological architectures able to trap, transport or transform chemicals in water or physiological media," says Dr Nitschke. "We hope that the control of the solubility properties and stability of these nanocontainers will allow others and us to build sophisticated systems for sensing low levels of biologically relevant molecules or environmental pollutants present in urine or the bloodstream in the context of clinical diagnosis. Likewise, our structures may be suitable as vehicles to transport dyes for diagnostic imaging, or to deliver drugs across macroscopic distances.

"Ultimately, we hope that such water-soluble architectures may serve as nanoreactors for the preparation of new molecules of interest, such as pharmaceuticals, or for the degradation of toxic pollutants such as residual medicines and pesticides that can be found in water streams."

This article is free to read in our open access, flagship journal Chemical Science: Edmundo Percastegui et al., Chem. Sci., 2019, Accepted Manuscript. DOI: 10.1039/C8SC05085F. You can access our 2018 ChemSci Picks in this article collection.