Many of the synthetic molecular machines1 that have been developed in the past 40 years are based on rotaxanes: molecules in which a ring-shaped component encircles a linear axle that is terminated with large ‘stoppers’ to prevent the ring from slipping off. The threading of the axle through the ring limits the motion of the ring to shuttling back and forth along the axle. Such shuttling has been used in a range of molecular machines that includes switches2, ratchets3, pumps4 and small-molecule synthesizers5. Rotaxanes in which more than one ring encircles the axle have also been made6, reminiscent of an abacus, but the rings have been unable to switch places. Writing in Nature Chemistry, Zhu et al.7 now report a system in which the rings can slip past one another, opening the way to new types of molecular machine.
To achieve a ring-through-ring shuttling motion, Zhu and colleagues assembled a rotaxane that contains two differently sized rings (Fig. 1). One has a circumference of 24 atoms, which is about as small as a ring can be in a rotaxane, whereas the other is almost twice as large at 42 atoms. Both rings form hydrogen bonds with nitrogen–hydrogen (N–H) units of the axle, and this enabled the authors to probe the rings’ movement using nuclear magnetic resonance (NMR) spectroscopy.
At room temperature, the authors observed two distinct N–H signals in the NMR spectrum of the rotaxane, because the signal for an N–H unit that is bonded to the small ring appears at a different frequency from that of an N–H unit bonded to the larger ring. This told Zhu and co-workers that the rings exchange places slowly at this temperature, or not at all. However, as the sample of rotaxane was heated, the signals began to broaden and then merged into a single peak. This finding confirmed that the rings change places quickly at elevated temperatures. The only way that this could have occurred is by the smaller ring passing through the larger one.
Zhu et al. determined that, at room temperature, the energy barrier that must be overcome for the rings to change places is about 52 kilojoules per mole of rotaxane, which corresponds to a shuttling rate of about 3,600 times per second. For comparison, in an analogous rotaxane that contains only the smaller ring, the ring hops between the N–H groups approximately 80,000 times per second, or roughly 20 times faster. On the basis of this comparison, the authors estimate that the ring-through-ring movement ‘costs’ about 12 kilojoules per mole — a considerable amount, but not as high as might have been expected.
The two-ringed rotaxane is remarkably simple compared with some of the synthetic molecular machines that have been produced so far. It might therefore seem surprising that this is the first time that a ring-through-ring shuttling process has been observed. However, to achieve their breakthrough, Zhu and colleagues had to bring together several key structural features.
First, the dramatic difference in the size of the rings is important for enabling shuttling to occur. Indeed, the authors produced another rotaxane analogue in which the larger ring was 12 atoms smaller and found that no ring-through-ring shuttling occurs, even at elevated temperatures.
Second, when large rings are used as components of rotaxanes, the stoppers on the ends of the axle must be extremely large to prevent the rings from slipping off. This demand can complicate the synthesis of rotaxanes because larger stoppers often cause problems with solubility, and their use typically adds further steps to an already complex synthetic route. Zhu et al. overcame these issues by using simple T-shaped stoppers that they had developed previously to make porous materials (known as metal–organic frameworks) that incorporate rotaxanes8.
Such structural issues highlight a limitation of the newly identified dynamic process: if rotaxane structures that show ring-through-ring shuttling must be so contrived, will it be possible to use ring-through-ring shuttling to develop molecular machines? It is to be hoped that the answer is ‘yes’, because ring-through-ring shuttling could bring an extra dimension to rotaxane-based switches. A potential application suggested by the authors is molecular-level weaving, in which ring-through-ring shuttling controls the entanglement of molecular threads — essentially, a small ring is used to pull a molecular chain through a larger ring, akin to threading a macroscopic needle.
Multi-ring rotaxanes could potentially also be used for information storage, in which data are encoded by the order of the rings on the axle. Before now, there was no major advantage to this approach compared with storing data in simpler molecules, because the ring order was fixed at the time of synthesis6. Zhu and colleagues’ work opens up the possibility of using external stimuli to order and reorder the rings, and therefore of writing and rewriting any encoded information.
Nature 557, 39-40 (2018)