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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.


  1. Schliwa, M. (ed.) Molecular Motors (Wiley-VCH, 2003).

    Google Scholar 

  2. Kelly, T. R., De Silva, H. & Silva, R. A. Unidirectional rotary motion in a molecular system. Nature 401, 150–152 (1999).

    CAS  Article  Google Scholar 

  3. Koumura, N., Zijlstra, R. W. J., van Delden, R. A., Harada, N. & Feringa, B. L. Light-driven monodirectional molecular rotor. Nature 401, 152–155 (1999).

    CAS  Article  Google Scholar 

  4. Leigh, D. A., Wong, J. K. Y., Dehez, F. & Zerbetto, F. Unidirectional rotation in a mechanically interlocked molecular rotor. Nature 424, 174–179 (2003).

    CAS  Article  Google Scholar 

  5. Thordarson, P., Bijsterveld, E. J. A., Rowan, A. E. & Nolte, R. J. M. Epoxidation of polybutadiene by a topologically linked catalyst. Nature 424, 915–918 (2003).

    CAS  Article  Google Scholar 

  6. van Delden, R. A. et al. Unidirectional molecular motor on a gold surface. Nature 437, 1337–1340 (2005).

    CAS  Article  Google Scholar 

  7. Fletcher, S. P., Dumur, F., Pollard, M. M. & Feringa, B. L. A reversible, unidirectional molecular rotary motor driven by chemical energy. Science 310, 80–82 (2005).

    CAS  Article  Google Scholar 

  8. Balzani, V. et al. Autonomous artificial nanomotor powered by sunlight. Proc. Natl Acad. Sci. USA 103, 1178–1183 (2006).

    CAS  Article  Google Scholar 

  9. Muraoka, T., Kinbara, K. & Aida, T. Mechanical twisting of a guest by a photoresponsive host. Nature 440, 512–515 (2006).

    CAS  Article  Google Scholar 

  10. Serreli, V., Lee, C.-F., Kay, E. R. & Leigh, D. A. A molecular information ratchet. Nature 445, 523–527 (2007).

    CAS  Article  Google Scholar 

  11. Kay, E. R., Leigh, D. A. & Zerbetto, F. Synthetic molecular motors and mechanical machines. Angew. Chem. Int. Ed. 46, 72–191 (2007).

    CAS  Article  Google Scholar 

  12. Sherman, W. B. & Seeman, N. C. A precisely controlled DNA biped walking device. Nano Lett. 4, 1203–1207 (2004).

    CAS  Article  Google Scholar 

  13. Shin, J.-S. & Pierce, N. A. A synthetic DNA walker for molecular transport. J. Am. Chem. Soc. 126, 10834–10835 (2004).

    CAS  Article  Google Scholar 

  14. Yin, P., Yan, H., Daniell, X. G., Turberfield, A. J. & Reif, J. H. A unidirectional DNA walker that moves autonomously along a track. Angew. Chem. Int. Ed. 43, 4906–4911 (2004).

    CAS  Article  Google Scholar 

  15. Tian, Y., He, Y., Chen, Y., Yin, P. & Mao, C. A DNAzyme that walks processively and autonomously along a one-dimensional track. Angew. Chem. Int. Ed. 44, 4355–4358 (2005).

    CAS  Article  Google Scholar 

  16. Pei, R. et al. Behavior of polycatalytic assemblies in a substrate-displaying matrix. J. Am. Chem. Soc. 128, 12693–12699 (2006).

    CAS  Article  Google Scholar 

  17. Yin, P., Choi, H. M. T., Calvert, C. R. & Pierce, N. A. Programming biomolecular self-assembly pathways. Nature 451, 318–322 (2008).

    CAS  Article  Google Scholar 

  18. Green, S. J., Bath, J. & Turberfield, A. J. Coordinated chemomechanical cycles: a mechanism for autonomous molecular motion. Phys. Rev. Lett. 101, 238101 (2008).

    CAS  Article  Google Scholar 

  19. Omabegho, T., Sha, R. & Seeman, N. C. A bipedal DNA Brownian motor with coordinated legs. Science 324, 67–71 (2009).

    CAS  Article  Google Scholar 

  20. Astumian, R. D. Design principles for Brownian molecular machines: how to swim in molasses and walk in a hurricane. Phys. Chem. Chem. Phys. 9, 5067–5083 (2007).

    CAS  Article  Google Scholar 

  21. Astumian, R. D. & Derényi, I. Fluctuation driven transport and models of molecular motors and pumps. Eur. Biophys. J. 27, 474–489 (1998).

    CAS  Article  Google Scholar 

  22. Rowan, S. J., Cantrill, S. J., Cousins, G. R. L., Sanders, J. K. M. & Stoddart, J. F. Dynamic covalent chemistry. Angew. Chem. Int. Ed. 41, 898–952 (2002).

    Article  Google Scholar 

  23. Corbett, P. T. et al. Dynamic combinatorial chemistry. Chem. Rev. 106, 3652–3711 (2006).

    CAS  Article  Google Scholar 

  24. Lehn, J.-M. From supramolecular chemistry towards constitutional dynamic chemistry and adaptive chemistry. Chem. Soc. Rev. 36, 151–160 (2007).

    CAS  Article  Google Scholar 

  25. Goral, V., Nelen, M. I., Eliseev, A. V. & Lehn, J.-M. Double-level ‘orthogonal’ dynamic combinatorial libraries on transition metal template. Proc. Natl Acad. Sci. USA 98, 1347–1352 (2001).

    CAS  Article  Google Scholar 

  26. Orrillo, A. G., Escalante, A. M. & Furlan, R. L. E. Covalent double level dynamic combinatorial libraries: selectively addressable exchange processes. Chem. Commun. 5298–5300 (2008).

  27. Rodriguez-Docampo, Z. & Otto, S. Orthogonal or simultaneous use of disulfide and hydrazone exchange in dynamic covalent chemistry in aqueous solution. Chem. Commun. 5301–5303 (2008).

  28. Otto, S., Furlan, R. L. E. & Sanders, J. K. M. Dynamic combinatorial libraries of macrocyclic disulfides in water. J. Am. Chem. Soc. 122, 12063–12064 (2000).

    CAS  Article  Google Scholar 

  29. Noji, H., Yasuda, R., Yoshida, M. & Kinosita, K. Direct observation of the rotation of F1-ATPase. Nature 386, 299–302 (1997).

    CAS  Article  Google Scholar 

  30. Vale, R. D. et al. Direct observation of single kinesin molecules moving along microtubules. Nature 380, 451–453 (1996).

    CAS  Article  Google Scholar 

  31. Case, R. B., Pierce, D. W., Hom-Booher, N., Hart, C. L. & Vale, R. D. The directional preference of kinesin motors is specified by an element outside of the motor catalytic domain. Cell 90, 959–966 (1997).

    CAS  Article  Google Scholar 

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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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