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.

A catalysis-driven artificial molecular pump

Abstract

All biological pumps are autonomous catalysts; they maintain the out-of-equilibrium conditions of the cell by harnessing the energy released from their catalytic decomposition of a chemical fuel1,2,3. A number of artificial molecular pumps have been reported to date4, but they are all either fuelled by light5,6,7,8,9,10 or require repetitive sequential additions of reagents or varying of an electric potential during each cycle to operate11,12,13,14,15,16. Here we describe an autonomous chemically fuelled information ratchet17,18,19,20 that in the presence of fuel continuously pumps crown ether macrocycles from bulk solution onto a molecular axle without the need for further intervention. The mechanism uses the position of a crown ether on an axle both to promote barrier attachment behind it upon threading and to suppress subsequent barrier removal until the ring has migrated to a catchment region. Tuning the dynamics of both processes20,21 enables the molecular machine22,23,24,25 to pump macrocycles continuously from their lowest energy state in bulk solution to a higher energy state on the axle. The ratchet action is experimentally demonstrated by the progressive pumping of up to three macrocycles onto the axle from bulk solution under conditions where barrier formation and removal occur continuously. The out-of-equilibrium [n]rotaxanes (characterized with n up to 4) are maintained for as long as unreacted fuel is present, after which the rings slowly de-thread. The use of catalysis to drive artificial molecular pumps opens up new opportunities, insights and research directions at the interface of catalysis and molecular machinery.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Structure and operation of a catalysis-driven artificial molecular pump.
Fig. 2: Macrocycle distribution in [n]rotaxane co-conformers.
Fig. 3: Fmoc removal, pseudorotaxane dethreading, and irreversible rotaxane formation experiments.
Fig. 4: Out-of-equilibrium state produced by the operation of pump 1.

Data availability

The data that support the findings of this study are available within the paper and its Supplementary Information, or are available from the Mendeley data repository (https://data.mendeley.com/) at https://doi.org/10.17632/r339vx45sz.1.

References

  1. 1.

    Skou, J. C. The identification of the sodium–potassium pump (Nobel Lecture). Angew. Chem. Int. Ed. 37, 2320–2328 (1998).

    CAS  Google Scholar 

  2. 2.

    Lodish, H. et al. Transport across cell membranes. In Molecular Cell Biology Vol. 4, Ch. 15 (W. H. Freeman, 2000).

  3. 3.

    Du, D. et al. Multidrug efflux pumps: structure, function and regulation. Nat. Rev. Microbiol. 16, 523–539 (2018).

    CAS  PubMed  Google Scholar 

  4. 4.

    Qiu, Y., Feng, Y., Guo, Q.-H., Astumian, R. D. & Stoddart, J. F. Pumps through the ages. Chem 6, 1952–1977 (2020).

    CAS  Google Scholar 

  5. 5.

    Steinberg-Yfrach, G. et al. Conversion of light energy to proton potential in liposomes by artificial photosynthetic reaction centres. Nature 385, 239–241 (1997).

    ADS  CAS  Google Scholar 

  6. 6.

    Bennett, I. M. et al. Active transport of Ca2+ by an artificial photosynthetic membrane. Nature 420, 398–401 (2002).

    ADS  CAS  Google Scholar 

  7. 7.

    Bhosale, S. et al. Photoproduction of proton gradients with π-stacked fluorophore scaffolds in lipid bilayers. Science 313, 84–86 (2006).

    ADS  CAS  Google Scholar 

  8. 8.

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

    ADS  CAS  Google Scholar 

  9. 9.

    Baroncini, M., Silvi, S., Venturi, M. & Credi, A. Photoactivated directionally controlled transit of a non-symmetric molecular axle through a macrocycle. Angew. Chem. Int. Ed. 51, 4223–4226 (2012).

    CAS  Google Scholar 

  10. 10.

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

    ADS  CAS  Google Scholar 

  11. 11.

    Cheng, C. et al. An artificial molecular pump. Nat. Nanotechnol. 10, 547–553 (2015).

    ADS  CAS  Google Scholar 

  12. 12.

    Pezzato, C. et al. An efficient artificial molecular pump. Tetrahedron 73, 4849–4857 (2017).

    CAS  Google Scholar 

  13. 13.

    Erbas-Cakmak, S. et al. Rotary and linear molecular motors driven by pulses of a chemical fuel. Science 358, 340–343 (2017).

    ADS  CAS  Google Scholar 

  14. 14.

    Pezzato, C. et al. Controlling dual molecular pumps electrochemically. Angew. Chem. Int. Ed. 57, 9325–9329 (2018).

    CAS  Google Scholar 

  15. 15.

    Qiu, Y. et al. A molecular dual pump. J. Am. Chem. Soc. 141, 17472–17476 (2019).

    CAS  Google Scholar 

  16. 16.

    Qiu, Y. et al. A precise polyrotaxane synthesizer. Science 368, 1247–1253 (2020).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Astumian, R. D. & Bier, M. Mechanochemical coupling of the motion of molecular motors to ATP hydrolysis. Biophys. J. 70, 637–653 (1996).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  18. 18.

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

    CAS  Google Scholar 

  19. 19.

    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  Google Scholar 

  20. 20.

    Astumian, R. D. Kinetic asymmetry allows macromolecular catalysts to drive an information ratchet. Nat. Commun. 10, 3837 (2019).

    ADS  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Astumian, R. D. How molecular motors work—insights from the molecular machinist’s toolbox: the Nobel prize in Chemistry 2016. Chem. Sci. 8, 840–845 (2017).

    CAS  Google Scholar 

  22. 22.

    Pezzato, C., Cheng, C., Stoddart, J. F. & Astumian, R. D. Mastering the non-equilibrium assembly and operation of molecular machines. Chem. Soc. Rev. 46, 5491–5507 (2017).

    CAS  Google Scholar 

  23. 23.

    Kassem, S. et al. Artificial molecular motors. Chem. Soc. Rev. 46, 2592–2621 (2017).

    CAS  Google Scholar 

  24. 24.

    Wang, Q., Chen, D. & Tian, H. Artificial molecular machines that can perform work. Sci. China Chem. 61, 1261–1273 (2018).

    CAS  Google Scholar 

  25. 25.

    Findlay, J. A. & Crowley, J. D. Functional nanomachines: recent advances in synthetic molecular machinery. Tetrahedron Lett. 59, 334–346 (2018).

    CAS  Google Scholar 

  26. 26.

    Coutrot, F. A focus on triazolium as a multipurpose molecular station for pH-sensitive interlocked crown-ether-based molecular machines. ChemistryOpen 4, 556–576 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Zheng, H. et al. A dual‐response [2]rotaxane based on a 1,2,3‐triazole ring as a novel recognition station. Chem. Eur. J. 15, 13253–13262 (2009).

    CAS  Google Scholar 

  28. 28.

    Fielden, S. D. P., Leigh, D. A., McTernan, C. T., Pérez-Saavedra, B. & Vitorica-Yrezabal, I. J. Spontaneous assembly of rotaxanes from a primary amine, crown ether and electrophile. J. Am. Chem. Soc. 140, 6049–6052 (2018).

    CAS  Google Scholar 

  29. 29.

    Tian, C., Fielden, S. D. P., Whitehead, G. F. S., Vitorica-Yrezabal, I. J. & Leigh, D. A. Weak functional group interactions revealed through metal-free active template rotaxane synthesis. Nat. Commun. 11, 744 (2020).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  30. 30.

    Tian, C., Fielden, S. D. P., Pérez-Saavedra, B., Vitorica-Yrezabal, I. J. & Leigh, D. A. Single-step enantioselective synthesis of mechanically planar chiral [2]rotaxanes using a chiral leaving group strategy. J. Am. Chem. Soc. 142, 9803–9808 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Denis, M. & Goldup, S. M. The active template approach to interlocked molecules: Principles, progress and applications. Nat. Rev. Chem. 1, 0061 (2017).

    CAS  Google Scholar 

  32. 32.

    Wilson, M. R. et al. An autonomous chemically fuelled small-molecule motor. Nature 534, 235–240 (2016).

    ADS  CAS  Google Scholar 

  33. 33.

    Fyfe, M. C. T. et al. Anion assisted self-assembly. Angew. Chem. Int. Ed. Engl. 36, 2068–2070 (1997).

    CAS  Google Scholar 

  34. 34.

    della Sala, F., Neri, S., Maiti, S., Chen, J. L.-Y. & Prins, L. J. Transient self-assembly of molecular nanostructures driven by chemical fuels. Curr. Opin. Biotechnol. 46, 27–33 (2017).

    Google Scholar 

  35. 35.

    van Rossum, S. A. P., Tena-Solsona, M., van Esch, J. H., Eelkema, R. & Boekhoven, J. Dissipative out-of-equilibrium assembly of man-made supramolecular materials. Chem. Soc. Rev. 46, 5519–5535 (2017).

    Google Scholar 

  36. 36.

    Ragazzon, G. & Prins, L. J. Energy consumption in chemical fuel-driven self-assembly. Nat. Nanotechnol. 13, 882–889 (2018).

    ADS  CAS  Google Scholar 

  37. 37.

    Rieß, B., Grötsch, R. & Boekhoven, J. The design of dissipative molecular assemblies driven by chemical reaction cycles. Chem 6, 552–578 (2020).

    Google Scholar 

  38. 38.

    Borsley, S., Leigh, D. A. & Roberts, B. M. W. A doubly kinetically-gated information ratchet autonomously driven by carbodiimide hydration. J. Am. Chem. Soc. 143, 4414–4420 (2021).

    CAS  Google Scholar 

  39. 39.

    Astumian, R. D. Irrelevance of the power stroke for the directionality, stopping force, and optimal efficiency of chemically driven molecular machines. Biophys. J. 108, 291–303 (2015).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Howard, J. Protein power strokes. Curr. Biol. 16, R517–R519 (2006).

    CAS  Google Scholar 

  41. 41.

    Hwang, W. & Karplus, M. Structural basis for power stroke vs. Brownian ratchet mechanisms of motor proteins. Proc. Natl Acad. Sci. USA 116, 19777–19785 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. 42.

    van Dijk, L., Tilby, M. J., Szpera, R., Smith, O. A., Bunce, H. A. P. & Fletcher, S. P. Molecular machines for catalysis. Nat. Rev. Chem. 2, 0117 (2018).

    Google Scholar 

  43. 43.

    Zhang, L., Marcos, V. & Leigh, D. A. Molecular machines with bio-inspired mechanisms. Proc. Natl Acad. Sci. USA 115, 9397–9404 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. 44.

    Biagini, C. et al. Dissipative catalysis with a molecular machine. Angew. Chem. Int. Ed. 58, 9876–9880 (2019).

    CAS  Google Scholar 

  45. 45.

    Astumian, R. D. et al. Non-equilibrium kinetics and trajectory thermodynamics of synthetic molecular pumps. Mater. Chem. 4, 1304–1314 (2020).

    CAS  Google Scholar 

  46. 46.

    Heard, A. W. & Goldup, S. M. Simplicity in the design, operation and applications of mechanically interlocked molecular machines. ACS Cent. Sci. 6, 117–128 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. 47.

    Aprahamian, I. The future of molecular machines. ACS Cent. Sci. 6, 347–358 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. 48.

    Moulin, E., Faour, L., Carmona-Vargas, C. C. & Giuseppone, N. From molecular machines to stimuli-responsive materials. Adv. Mater. 32, 1906036 (2020).

    CAS  Google Scholar 

Download references

Acknowledgements

We thank the Engineering and Physical Sciences Research Council (EPSRC; grant number EP/P027067/1) and the European Research Council (ERC; Advanced Grant number 786630) for funding. We also thank the University of Manchester’s Department of Chemistry Services for mass spectrometry. D.A.L. is a Royal Society Research Professor.

Author information

Affiliations

Authors

Contributions

S.A. and S.D.P.F. carried out the synthesis and characterization studies. 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 interests.

Additional information

Peer review information Nature thanks R. Dean Astumian and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Peer reviewer reports are available.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information

This Supplementary Information file contains the following sections: Abbreviations; General Information. Experimental Data; NMR Spectra; Supplementary Text (Optimisation of pumping conditions); and Supplementary References.

Peer Review File

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Amano, S., Fielden, S.D.P. & Leigh, D.A. A catalysis-driven artificial molecular pump. Nature 594, 529–534 (2021). https://doi.org/10.1038/s41586-021-03575-3

Download citation

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links