Artificial molecular machines are scientifically satisfying structures.
Studying molecules is a fascinating intellectual endeavour. Within a molecule, each atom is in exactly the right position to accomplish something useful. There is beauty in appreciating such a sense of purpose and chemists have developed a soft spot for beautiful molecules, recognizing their simplicity, elegance and precise atomic arrangements. Whereas the instinct of the organic chemist may be to find the most economical path to make a molecular structure, the instinct of the physical chemist is to see what a molecule can do.
There are molecules walking on tracks, molecules that can toggle between configurations and properties, molecules that can do work on the environment, molecules that can catalyse their own synthesis, molecules that can propel themselves in solution and even molecules that can assemble building blocks to make another molecule. In many cases, these examples are inspired by natural molecules, such as myosin, ATP and rhodopsin. Being able to reproduce the behaviours of these natural molecules, even in a minimalistic form (any of these synthetic molecules pale in comparison to the sophistication of biomolecules), teaches us something about natural processes, for making is understanding.
The latest addition to this conceptual journey in the molecular world can be found in this issue in a Letter by De Bo et al.1. The authors have made a molecule that can synthesize a second molecule, which in turn assumes a characteristic conformation that can catalyse the formation of a third molecule. In other words, the work shows a molecule that can synthesize a chemically functional molecule. This is the closest we have been to being able to mimic the behaviour of a ribosome.
The initial molecule is a rotaxane, the axle of which is a polymer functionalized with leucine esters. The ring of the rotaxane travels the polymeric backbone, picking up amino acid residues to form an oligopeptide. This oligomer, together with the ring to which it is attached, slips off from the axle and folds itself into an alpha-helix, which finally catalyses the formation of an asymmetric epoxide from a chalcone in solution. The similarities with a ribosome are obvious: the molecule transforms the information contained in the polymer backbone into the secondary structure of a new molecule, which then does something chemically useful.
Some could see the resemblance of this approach with a previous system in which a similar rotaxane could pick up three amino acids and make a tripeptide before slipping it off the axle2. The main novelty here is the incorporation of the polymer backbone. The formation of the epoxide (via the Julià–Colonna reaction) can be carried out using much cheaper compounds than a rotaxane. Plus, the ring takes an average of 96 h to move along the backbone, not exactly a speedy process!
It is important to understand, we believe, that the point of making molecular machines is not — as of yet — to make practically useful structures. As has been said: “there is as yet no task that can be performed by a synthetic molecular machine that cannot be done more effectively another way”3. However, they remain a source of inspiration for nanoscale science. The simple fact that we can take an amazingly complicated natural process, strip it down to its essential components and build an artificial system that can reproduce its behaviour is scientifically satisfying. And there is beauty in that.
De Bo, G. et al. Nat. Nanotech. https://doi.org/10.1038/s41565-018-0105-3 (2018).
Lewandowski, B. et al. Science 339, 189–193 (2013).
Leigh, D. A. Angew. Chem. Int. Ed. Engl. 55, 14506–14508 (2016).