Biting chemistry

US chemists have constructed a molecule that bites its own tail and in so doing can trap other small molecules within the cavity that results. Fed a diet of zinc ions the "ouroborand", reported in Angewandte Chemie, will release its bite to let other smaller molecules into the central cavity. Remove the zinc ions and it loses its grip on the guest. Nuclear magnetic resonance spectroscopy was used to characterise the components and the process.

Julius Rebek, Jr. and Fabien Durola of The Scripps Research Institute, in La Jolla, California, USA explain that the ouroboros (Greek for "tail devourer") is a motif found in many cultures: a snake biting its own tail, it symbolizes eternity and never-ending cycles. Indeed, the image was said to have inspired nineteenth century chemist August Kekule in his quest for the structure of benzene.

Rebek and colleagues have now constructed a supramolecular tail devourer, and dubbed it an "ouroborand". They suggest that this compound is another molecular machine in a long line of recent developments in which macroscopic behaviour is scaled down to the molecular level. "Molecular devices reproduce on the nanoscale functions of macroscopic objects, at least notionally," the team says. These molecular machines include self-assembled capsules that act as reaction flasks, catenanes and rotaxanes that shuttle molecular units from place to place along or around a molecule, and cylindrical molecular containers and rotors.

They point out that on/off switches involving extension and contraction motions are among the oldest molecular devices. Their ouroborand functions as just such a nanocontainer with a built-in switch that regulates entry to and exit from the central cavity. The team further explains that it is intermolecular forces and the appropriate filling of space that usually control the binding of guests within such systems rather than the conventional covalent bonds of organic chemistry.

The novel ouroborand structure is made up of various components that work together to endow it with the ability to control entry and exit of a guest molecule. The molecule was constructed in ten main reaction steps from off-the-shelf chemicals and the final product characterized by proton NMR spectroscopy and mass spectrometry. A central macrocyclic unit forms the cavity, the rim of which is flanked on three sides by units bearing nitrogen and oxygen atoms that can lock together through hydrogen bonding to form the macrocycle into a cup shape. On its fourth side is a bypyridyl ligand with a "dangling" cyclohexane unit. It is this moiety that acts as the tail of the ouroborand that is bitten by the mouth of the cavity. The bipyridyl unit is a switchable rotor.

When the team adds zinc ions to a solution of the ouroborand, the cavity is opened as the rotor has two binding sites for zinc ions but in order for it to bind to two at once it must rotate through a half turn. The zinc coupling arm turns with it, which causes the tail end to be pulled out of the container. The vessel is now free and accessible to other molecules; it is switched to open. Removing the zinc ions from the solution allows the rotor to move back to its original position, which in the absence of zinc is sterically less hindered, and the tail end closes the cavity once again, excluding foreign molecules from the container. Technically, the entropic advantage of the tethered cyclohexane prevents entry of other guests.

The team also used proton NMR to study this "autophagic" behaviour in different deuterated solvents. They explain that because the molecule's walls incorporate eight aromatic rings, guest molecules within are strongly shielded to below d=0 ppm, which proves whether the cavity is empty or not.

"To place these results in an historical perspective, we note that bipyridyl rotors were among the earliest chemical models - of allosteric behaviour of proteins - how binding at a remote site can alter the behaviour of an active site," the researchers say. Other examples of metal chelation of bipyridyl cavity molecules that results in changes in structure and behaviour emphasise, together with the Rebek work, that bipyridyl/metal chelation are "reliable tools for forging tomorrow's molecular machinery".

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.