Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Pick-up, transport and release of a molecular cargo using a small-molecule robotic arm

Abstract

Modern-day factory assembly lines often feature robots that pick up, reposition and connect components in a programmed manner. The idea of manipulating molecular fragments in a similar way has to date only been explored using biological building blocks (specifically DNA). Here, we report on a wholly artificial small-molecule robotic arm capable of selectively transporting a molecular cargo in either direction between two spatially distinct, chemically similar, sites on a molecular platform. The arm picks up/releases a 3-mercaptopropanehydrazide cargo by formation/breakage of a disulfide bond, while dynamic hydrazone chemistry controls the cargo binding to the platform. Transport is controlled by selectively inducing conformational and configurational changes within an embedded hydrazone rotary switch that steers the robotic arm. In a three-stage operation, 79–85% of 3-mercaptopropanehydrazide molecules are transported in either (chosen) direction between the two platform sites, without the cargo at any time fully dissociating from the machine nor exchanging with other molecules in the bulk.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Multi-stage operation of a bidirectional small-molecule transporter system, 1, that uses a rotary switch to control a molecular robotic arm.
Figure 2: Synthesis of transporter–cargo conjugates Z-2-left and EZ-1-left.
Figure 3: Partial 1H NMR (600 MHz, 295 K, CD2Cl2) spectra of the transporter–cargo conjugates at distinctive stages of operation.
Figure 4: Operation of the molecular transporter to reposition a 3-mercaptopropanehydrazide cargo from blue to green or green to blue platform sites.
Figure 5: Presumed intermediates in the rotary switching 26 and cargo transport mechanism.

Similar content being viewed by others

References

  1. Feynman, R. P. There's plenty of room at the bottom. Eng. Sci. 23, 22–36 (1960).

    Google Scholar 

  2. Drexler, K. E. Molecular engineering: an approach to the development of general capabilities for molecular manipulation. Proc. Natl Acad. Sci. USA 78, 5275–5278 (1981).

    Article  CAS  Google Scholar 

  3. Drexler, K. E. Nanosystems: Molecular Machinery, Manufacturing, and Computation (Wiley, 1992).

    Google Scholar 

  4. Kumagai, T. et al. Controlling intramolecular hydrogen transfer in a porphycene molecule with single atoms or molecules located nearby. Nature Chem. 6, 41–46 (2014).

    Article  CAS  Google Scholar 

  5. Smalley, R. E. Of chemistry, love and nanobots. Sci. Am. 285, 76–77 (2001).

    Article  CAS  Google Scholar 

  6. Whitesides, G. M. The once and future nanomachine. Sci. Am. 285, 78–83 (2001).

    Article  CAS  Google Scholar 

  7. Jones, R. A. L. Soft Machines: Nanotechnology and Life (Oxford Univ. Press, 2004).

    Google Scholar 

  8. Maier, T., Leibundgut, M. & Ban, N. The crystal structure of a mammalian fatty acid synthase. Science 321, 1315–1322 (2008).

    Article  CAS  Google Scholar 

  9. Brignole, E. J., Smith, S. & Asturias, F. J. Conformational flexibility of metazoan fatty acid synthase enables catalysis. Nature Struct. Mol. Biol. 16, 190–197 (2009).

    Article  CAS  Google Scholar 

  10. Chan, D. I. & Vogel, H. J. Current understanding of fatty acid biosynthesis and the acyl carrier protein. Biochem. J. 430, 1–19 (2010).

    Article  CAS  Google Scholar 

  11. Ding, B. & Seeman, N. C. Operation of a DNA robot arm inserted into a 2D DNA crystalline substrate. Science 314, 1583–1585 (2006).

    Article  CAS  Google Scholar 

  12. Gu, H., Chao, J., Xiao, S.-J. & Seeman, N. C. A proximity-based programmable DNA nanoscale assembly line. Nature 465, 202–205 (2010).

    Article  CAS  Google Scholar 

  13. von Delius, M. & Leigh, D. A. Walking molecules. Chem. Soc. Rev. 40, 3656–3676 (2011).

    Article  CAS  Google Scholar 

  14. Berná, J. et al. Macroscopic transport by synthetic molecular machines. Nature Mater. 4, 704–710 (2005).

    Article  Google Scholar 

  15. Liu, Y. et al. Linear artificial molecular muscles. J. Am. Chem. Soc. 127, 9745–9759 (2005).

    Article  CAS  Google Scholar 

  16. Eelkema, R. et al. Molecular machines: nanomotor rotates microscale objects. Nature 440, 163 (2006).

    Article  CAS  Google Scholar 

  17. Li, Q. et al. Macroscopic contraction of a gel induced by the integrated motion of light-driven molecular motors. Nature Nanotech. 10, 161–165 (2015).

    Article  Google Scholar 

  18. Kay, E. R. & Leigh, D. A. Rise of the molecular machines. Angew. Chem. Int. Ed. 54, 10080–10088 (2015).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  20. Erbas-Cakmak, S., Leigh, D. A., McTernan, C. T. & Nussbaumer, A. L. Artificial molecular machines. Chem. Rev. 115, 10081–10206 (2015).

    Article  CAS  Google Scholar 

  21. 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).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  23. von Delius, M., Geertsema, E. M., Leigh, D. A. & Tang, D.-T. D. Design, synthesis, and operation of small molecules that walk along tracks. J. Am. Chem. Soc. 132, 16134–16145 (2010).

    Article  CAS  Google Scholar 

  24. Barrell, M. J., Campaña, A. G., von Delius, M., Geertsema, E. M. & Leigh, D. A. Light-driven transport of a molecular walker in either direction along a molecular track. Angew. Chem. Int. Ed. 50, 285–290 (2011).

    Article  CAS  Google Scholar 

  25. Feringa, B. L. & Browne, W. R. (eds) Molecular Switches 2nd edn (Wiley-VCH, 2011).

    Book  Google Scholar 

  26. Su, X. & Aprahamian, I. Switching around two axles: controlling the configuration and conformation of a hydrazone-based switch. Org. Lett. 13, 30–33 (2011).

    Article  CAS  Google Scholar 

  27. Su, X., Robbins, T. F. & Aprahamian, I. Switching through coordination-coupled proton transfer. Angew. Chem. Int. Ed. 50, 1841–1844 (2011).

    Article  CAS  Google Scholar 

  28. Ray, D., Foy, J. T., Hughes, R. P. & Aprahamian, I. A switching cascade of hydrazone-based rotary switches through coordination-coupled proton relays. Nature Chem. 4, 757–762 (2012).

    Article  CAS  Google Scholar 

  29. Japp, F. R. & Klingemann, F. Ueber benzolazo- und benzolhydrazofettsäuren. Ber. Dtsch. Chem. Ges. 20, 2942–2944 (1887).

    Article  Google Scholar 

  30. Landge, S. L. et al. Isomerization mechanism in hydrazone-based rotary switches: lateral shift, rotation, or tautomerization? J. Am. Chem. Soc. 133, 9812–9823 (2011).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  32. Hernández, J. V., Kay, E. R. & Leigh, D. A. A reversible synthetic rotary molecular motor. Science 306, 1532–1537 (2004).

    Article  Google Scholar 

  33. Ragazzon, G., Baroncini, M., Silvi, S., Venturi, M. & Credi, A. Light-powered autonomous and directional molecular motion of a dissipative self-assembling system. Nature Nanotech. 10, 70–75 (2015).

    Article  CAS  Google Scholar 

  34. Lewandowski, B. et al. Sequence-specific peptide synthesis by an artificial small-molecule machine. Science 339, 189–193 (2013).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors acknowledge the Engineering and Physical Sciences Research Council (EPSRC) for funding and the EPSRC National Mass Spectrometry Service Centre (Swansea, UK) for high-resolution mass spectrometry.

Author information

Authors and Affiliations

Authors

Contributions

A.M. and D.A.L. planned the project. S.K., A.T.L.L., A.M. and J.S. carried out the experimental work. D.A.L. directed the research. All authors contributed to the analysis of the results and the writing of the manuscript.

Corresponding author

Correspondence to David A. Leigh.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary information

Supplementary information (PDF 7758 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kassem, S., Lee, A., Leigh, D. et al. Pick-up, transport and release of a molecular cargo using a small-molecule robotic arm. Nature Chem 8, 138–143 (2016). https://doi.org/10.1038/nchem.2410

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchem.2410

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing