Work from Jeremy Sanders’ lab has generated novel molecules that assemble and link together to tie themselves in knots. The results, published in Science in November, represent a major step forward towards understanding the complex non-covalent chemistry that determines the assembly of larger molecules such as proteins.
Molecules designed to be rings on rods (rotaxanes) or interlocked rings (catenanes) have long been the target of supramolecular chemists, using non-covalent forces to self-assemble molecules into higher order structures. More recent targets successfully synthesised include Borromean Rings and the field is sufficiently developed for some groups to generate molecular electronic devices based upon these chemistries.
But how much do we really understand the self-assembly process involved this assembly, from a fundamental thermodynamic and structural perspective? Until now these complex interlocked structures have required help to direct their assembly by templating, using metal ions for example.
Work from the Sanders Lab published recently in Science, describes a remarkable, new, knotted structure, a trefoil knot, that emerged from some dynamic combinatorial libraries of naphthalene diimides linked with amino acids which exchanging ‘partner’ building blocks through disulphide bond interchange. This Dynamic Combinatorial Chemistry (DCC) approach allows the molecules themselves to explore different assemblies in solution, with those attaining lowest thermodynamic energy persisting in the mixture once it has reached equilibrium.
Check out what other leading chemists have said about these results in Science itself, in C&E News, and the RSC Chemistry World, where you can also find a video to take you around the structure of the Trefoil Knot.
The work, led by Jeremy and Dan PantoÅ, now at Bath University, shows how the hydrophobic effect is a dominant thermodynamic driving force in this context. In this respect, of course, the supramolecular chemistry involved is a simpler example of exactly the same knotting observed in some folded proteins. Indeed, the assembly (folding) process by which some proteins adopt their knotted structure has been the target of a lot of Sophie Jackson’s research in recent years.
So as well as having significant impact on the supramolecular world, the new work, involving much simpler molecules, will help protein folders understand the complex topological processes involved in their assembly by allowing systematic variations to the molecules and the experimental conditions. The size of the assemblies involved will also whet the appetite of our computational chemists who will no doubt already be coding their computers to search the conformational and energy landscapes of these knotted molecules.
It just goes to prove how research in this department tackles the knottiest of fundamental problems.