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A synthetic small molecule that can walk down a track


Although chemists have made small-molecule rotary motors, to date there have been no reports of small-molecule linear motors. Here we describe the synthesis and operation of a 21-atom two-legged molecular unit that is able to walk up and down a four-foothold molecular track. High processivity is conferred by designing the track-binding interactions of the two feet to be labile under different sets of conditions such that each foot can act as a temporarily fixed pivot for the other. The walker randomly and processively takes zero or one step along the track using a ‘passing-leg’ gait each time the environment is switched between acid and base. Replacing the basic step with a redox-mediated, disulfide-exchange reaction directionally transports the bipedal molecules away from the minimum-energy distribution by a Brownian ratchet mechanism. The ultimate goal of such studies is to produce artificial, linear molecular motors that move directionally along polymeric tracks to transport cargoes and perform tasks in a manner reminiscent of biological motor proteins.

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Figure 1: Binding requirements for the processive migration of a two-legged walker molecule (red) along a track that features two possible binding sites (green and blue) for each foot.
Figure 2: Synthesis and operation of molecular walker–track conjugate 1,2-1 under different sets of conditions (acid–base) for reversible covalent bonding of each foot with footholds on the track.
Figure 3: Partial 1H NMR (500 MHz, CDCl3, 298 K) spectra of molecular track 4 and the four walker–track positional isomers 1,2-1, 2,3-1, 3,4-1 and 1,4-1.
Figure 4: Dynamic behaviour of molecular walker–track conjugates 1,2-1 and 3,4-1, each under cycling of the conditions (acid–base) for reversible covalent bonding of each foot with pairs of footholds on the track.
Figure 5: Processive directionally biased walk from 1,2-1 under cycling of conditions (acid–redox) for covalent bonding of each foot with pairs of footholds on the track.


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We thank the Engineering and Physical Sciences Research Council (EPSRC) National Mass Spectrometry Service Centre (Swansea, UK) for high-resolution mass spectrometry and Juraj Bella for assistance with high-field NMR spectroscopy. This research was funded through the European Research Council Advanced Grant WalkingMols. D.A.L. is an EPSRC Senior Research Fellow and holds a Royal Society–Wolfson Research Merit Award.

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M.v.D. and E.M.G. carried out the experimental work. All the authors contributed to the design of the experiments, the analysis of the data and the writing of the paper.

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Correspondence to David A. Leigh.

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The authors declare no competing financial interests.

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von Delius, M., Geertsema, E. & Leigh, D. A synthetic small molecule that can walk down a track. Nature Chem 2, 96–101 (2010).

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