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:

Chiral catalysis-driven rotary molecular motors

Nature Chemistry (2026)Cite this article

Subjects

Abstract

The structural anisotropy necessary to distinguish clockwise from counterclockwise motions in motor-molecules continuously rotating about a covalent single bond has previously been supplied by chiral fuelling systems or by enzymes. Here we report a class of rotary motors in which, like motor proteins, structural asymmetry in the motor itself causes directional rotary catalysis. A single stereogenic centre in azaindole–phenylethanoic acid motors is sufficient to produce diastereomeric intermediates of atropisomeric conformations in the catalytic cycle, generating 8:1 clockwise:counterclockwise directional bias in the motor’s rotary catalysis of diisopropylcarbodiimide hydration (motor substituent PhCH2–). One enantiomer of a chiral hydrolysis promoter increases the directionality to 30:1 for clockwise rotation (motor substituent CH3–), while the other enantiomer reverses the direction to 1:2 clockwise:counterclockwise. The experimental demonstration that a chiral molecular motor can be powered by a chemical fuel to rotate either with, or counter to, the motor’s dominant power stroke informs the understanding of how chemical energy is transduced through catalysis, the fundamental process that powers biology.

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

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

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

Fig. 1: Chemical structure and chemomechanical catalytic cycle of chiral azaindole–phenylethanoic acid rotary motor 1 and model 2.
Fig. 2: Equilibrium and fuelled (with achiral DIC and DMAP) steady-state distributions of model motor 2.
Fig. 3: Fuelling kinetics of 2 and extrapolation of the rates to the experimental data obtained for 1.
Fig. 4: Curtin–Hammett principle reaction profiles for the chemomechanical cycle of motor 1.
Fig. 5: The effect of structural changes on motor directionality.

Similar content being viewed by others

Data availability

Crystallographic data for the structures reported in this Article have been deposited at the Cambridge Crystallographic Data Centre, under deposition numbers CCDC 2338856 (2-IV), 2338857 (S12-I), 2338858 (2-I), 2338859 (S8-I) and 2338860 (S8-IV). These data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html. 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/) via https://doi.org/10.17632/kby9y39k2h.1 (ref. 55).

References

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

    Article  PubMed  CAS  Google Scholar 

  2. Amano, S., Fielden, S. D. P. & Leigh, D. A. A catalysis-driven artificial molecular pump. Nature 594, 529–534 (2021).

    Article  PubMed  CAS  Google Scholar 

  3. Borsley, S., Kreidt, E., Leigh, D. A. & Roberts, B. M. W. Autonomous fuelled directional rotation about a covalent single bond. Nature 604, 80–85 (2022).

    Article  PubMed  CAS  Google Scholar 

  4. Liu, E. et al. A molecular information ratchet using a cone-shaped macrocycle. Chem 9, 1147–1163 (2023).

    Article  CAS  Google Scholar 

  5. Berreur, J. et al. Redox-powered autonomous directional C–C bond rotation under enzyme control. Nature 644, 96–101 (2025).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Gallagher, J. M., Roberts, B. M. W., Borsley, S. & Leigh, D. A. Conformational selection accelerates catalysis by an organocatalytic molecular motor. Chem 10, 855–866 (2024).

    Article  CAS  Google Scholar 

  7. Wang, P.-L. et al. Transducing chemical energy through catalysis by an artificial molecular motor. Nature 637, 594–600 (2025).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Liu, H.-K. et al. Structural influence of the chemical fueling system on a catalysis-driven rotary molecular motor. J. Am. Chem. Soc. 147, 8785–8795 (2025).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Wang, P.-L. et al. A catalysis-driven dual molecular motor. J. Am. Chem. Soc. 147, 10690–10697 (2025).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Liu, H.-K. et al. In situ quantification of directional rotation by a catalysis-driven azaindole‑N‑oxide−phenoic acid molecular motor. J. Am. Chem. Soc. 147, 29534–29541 (2025).

    Article  PubMed  CAS  Google Scholar 

  11. Liu, E., Daou, D., Hasenknopf, B., Vives, G. & Sollogoub, M. Not going back: unidirectional movement by intramolecular one-way ratcheting of functionalized cyclodextrin. Chem 11, 102623 (2025).

    Article  CAS  Google Scholar 

  12. Schliwa, M. & Woehlke, G. Molecular motors. Nature 422, 759–765 (2003).

    Article  PubMed  CAS  Google Scholar 

  13. Biagini, C. & Di Stefano, S. Abiotic chemical fuels for the operation of molecular machines. Angew. Chem. Int. Ed. 59, 8344–8354 (2020).

    Article  CAS  Google Scholar 

  14. Borsley, S., Leigh, D. A. & Roberts, B. M. W. Chemical fuels for molecular machinery. Nat. Chem. 14, 728–738 (2022).

    Article  PubMed  CAS  Google Scholar 

  15. Sangchai, T., Al Shehimy, S., Penocchio, E. & Ragazzon, G. Artificial molecular ratchets: tools enabling endergonic processes. Angew. Chem. Int. Ed. 62, e202309501 (2023).

    Article  CAS  Google Scholar 

  16. Borsley, S., Leigh, D. A. & Roberts, B. M. W. Molecular ratchets and kinetic asymmetry: giving chemistry direction. Angew. Chem. Int. Ed. 63, e202400495 (2024).

    Article  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  18. Kelly, T. R. et al. Progress toward a rationally designed, chemically powered rotary molecular motor. J. Am. Chem. Soc. 129, 376–386 (2007).

    Article  PubMed  CAS  Google Scholar 

  19. Lin, Y., Dahl, B. J. & Branchaud, B. P. Net directed 180° aryl-aryl bond rotation in a prototypical achiral biaryl lactone synthetic molecular motor. Tetrahedron Lett. 46, 8359–8362 (2005).

    Article  CAS  Google Scholar 

  20. 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).

    Article  PubMed  CAS  Google Scholar 

  21. Mondal, A., Toyoda, R., Costil, R. & Feringa, B. L. Chemically driven rotatory molecular machines. Angew. Chem. Int. Ed. 61, e202206631 (2022).

    Article  CAS  Google Scholar 

  22. Han, T.-J., Ke, X.-Y., Wang, M.-C., Ni, S.-F. & Mei, G.-J. A chemically powered rotary molecular motor based on reversible oxazepine formation. Angew. Chem. Int. Ed. 64, e202418933 (2025).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  24. 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  PubMed  CAS  Google Scholar 

  25. Abendroth, J. M., Bushuyev, O. S., Weiss, P. S. & Barrett, C. J. Controlling motion at the nanoscale: rise of the molecular machines. ACS Nano 9, 7746–7768 (2015).

    Article  PubMed  CAS  Google Scholar 

  26. Lancia, F., Ryabchun, A. & Katsonis, N. Life-like motion driven by artificial molecular machines. Nat. Rev. Chem. 3, 536–551 (2019).

    Article  CAS  Google Scholar 

  27. Amano, S., Borsley, S., Leigh, D. A. & Sun, Z. Chemical engines: driving systems away from equilibrium through catalyst reaction cycles. Nat. Nanotechnol. 16, 1057–1067 (2021).

    Article  PubMed  CAS  Google Scholar 

  28. Amano, S. & Hermans, T. M. Repurposing a catalytic cycle for transient self-assembly. J. Am. Chem. Soc. 146, 23289–23296 (2024).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  31. Astumian, R. D. Kinetic asymmetry and directionality of nonequilibrium molecular systems. Angew. Chem. Int. Ed. 63, e202306569 (2024).

    Article  CAS  Google Scholar 

  32. 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).

    Article  PubMed  CAS  Google Scholar 

  33. Sheng, J. et al. Formylation boosts the performance of light-driven overcrowded alkene-derived rotary molecular motors. Nat. Chem. 16, 1330–1338 (2024).

    Article  PubMed  CAS  Google Scholar 

  34. Walsh, C. T., Tu, B. P. & Tang, Y. Eight kinetically stable but thermodynamically activated molecules that power cell metabolism. Chem. Rev. 118, 1460–1494 (2018).

    Article  PubMed  CAS  Google Scholar 

  35. Dahl, B. J. & Branchaud, B. P. Synthesis and characterization of a functionalized chiral biaryl capable of exhibiting unidirectional bond rotation. Tetrahedron Lett. 45, 9599–9602 (2004).

    Article  CAS  Google Scholar 

  36. Dahl, B. J. & Branchaud, B. P. 180° unidirectional bond rotation in a biaryl lactone artificial molecular motor prototype. Org. Lett. 8, 5841–5844 (2006).

    Article  PubMed  CAS  Google Scholar 

  37. Collins, B. S. L., Kistemaker, J. C. M., Otten, E. & Feringa, B. L. A chemically powered unidirectional rotary molecular motor based on a palladium redox cycle. Nat. Chem. 8, 860–866 (2016).

    Article  CAS  Google Scholar 

  38. Zhang, Y. et al. A chemically driven rotary molecular motor based on reversible lactone formation with perfect unidirectionality. Chem 6, 2420–2429 (2020).

    Article  CAS  Google Scholar 

  39. Leigh, D. A. Reaction: of myths, misconceptions and motors—a matter of equilibrium. Chem 11, 102745 (2025).

    Article  CAS  Google Scholar 

  40. Astumian, R. D. Trajectory and cycle-based thermodynamics and kinetics of molecular machines: the importance of microscopic reversibility. Acc. Chem. Res. 51, 2653–2661 (2018).

    Article  PubMed  CAS  Google Scholar 

  41. 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).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Amano, S. et al. Using catalysis to drive chemistry away from equilibrium: relating kinetic asymmetry, power strokes, and the Curtin–Hammett principle in Brownian ratchets. J. Am. Chem. Soc. 144, 20153–20164 (2022).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Penocchio, E., Gu, G., Albaugh, A. & Gingrich, T. R. Power strokes in molecular motors: predictive, irrelevant, or somewhere in between?. J. Am. Chem. Soc. 147, 1063–1073 (2025).

    Article  PubMed  CAS  Google Scholar 

  44. Kariyawasam, L. S. & Hartley, C. S. Dissipative assembly of aqueous carboxylic acid anhydrides fueled by carbodiimides. J. Am. Chem. Soc. 139, 11949–11955 (2017).

    Article  PubMed  CAS  Google Scholar 

  45. Schwarz, P. S., Tena-Solsona, M., Daia, K. & Boekhoven, J. Carbodiimide-fueled catalytic reaction cycles to regulate supramolecular processes. Chem. Commun. 58, 1284–1297 (2022).

    Article  CAS  Google Scholar 

  46. Binks, L. et al. The role of kinetic asymmetry and power strokes in an information ratchet. Chem 9, 2902–2917 (2023).

    Article  CAS  Google Scholar 

  47. Kariyawasam, L. S., Hossain, M. M. & Hartley, C. S. The transient covalent bond in abiotic nonequilibrium systems. Angew. Chem. Int. Ed. 60, 12648–12658 (2021).

    Article  CAS  Google Scholar 

  48. Griehl, C., Kolbe, A. & Merkel, S. Quantitative description of epimerization pathways using the carbodiimide method in the synthesis of peptides. J. Chem. Soc. Perkin Trans. 2, 2525–2529 (1996).

    Article  Google Scholar 

  49. Seeman, J. I. Effect of conformational change on reactivity in organic chemistry. Evaluations, applications, and extensions of Curtin–Hammett Winstein–Holness kinetics. Chem. Rev. 83, 83–134 (1983).

    Article  CAS  Google Scholar 

  50. Feringa, B. L. The art of building small: from molecular switches to motors (Nobel Lecture). Angew. Chem. Int. Ed. 56, 11060–11078 (2017).

    Article  CAS  Google Scholar 

  51. Greb, L. & Lehn, J.-M. Light-driven molecular motors: imines as four-step or two-step unidirectional rotors. J. Am. Chem. Soc. 136, 13114–13117 (2014).

    Article  PubMed  CAS  Google Scholar 

  52. Uhl, E., Mayer, P. & Dube, H. Active and unidirectional acceleration of biaryl rotation by a molecular motor. Angew. Chem. Int. Ed. 59, 5730–5737 (2020).

    Article  CAS  Google Scholar 

  53. Richards, C. J. & Arthurs, R. A. Catalyst optimisation for asymmetric synthesis by ligand chirality element addition: a perspective on stereochemical cooperativity. Chem. Eur. J. 23, 11460–11478 (2017).

    Article  PubMed  CAS  Google Scholar 

  54. Xie, M.-S. et al. Rational design of 2-substituted DMAP-N-oxides as acyl transfer catalysts: dynamic kinetic resolution of azlactones. J. Am. Chem. Soc. 142, 19226–19238 (2020).

    Article  PubMed  CAS  Google Scholar 

  55. Liu, H.-K. et al. Chiral catalysis-driven rotary molecular motors. Mendeley Data https://doi.org/10.17632/kby9y39k2h.1 (2026).

Download references

Acknowledgements

We thank S. Amano for initial discussions regarding the concept of a chiral rotary motor, and S. Amano, T. W. Mrad and L. Binks for work on early prototypes of chiral catalysis-driven rotary molecular motors. This work was funded by the Engineering and Physical Sciences Research Council (EP/P027067/1, D.A.L.; EP/V007580/1, R.W.A.) and the European Research Council (advanced grant number 786630; D.A.L.). S.B. is a Royal Society University Research Fellow. D.A.L. is a Royal Society Research Professor. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

Author information

Authors and Affiliations

  1. Department of Chemistry, University of Manchester, Manchester, UK

    Hua-Kui Liu, Benjamin M. W. Roberts, Stefan Borsley, Ralph W. Adams, George F. S. Whitehead, Avantika Hasija & David A. Leigh

  2. Department of Chemical Science, University of Padua, Padua, Italy

    Benjamin M. W. Roberts

  3. Department of Chemistry, Durham University, Durham, UK

    Stefan Borsley

  4. School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, China

    David A. Leigh

Authors
  1. Hua-Kui Liu
    View author publications

    Search author on:PubMed Google Scholar

  2. Benjamin M. W. Roberts
    View author publications

    Search author on:PubMed Google Scholar

  3. Stefan Borsley
    View author publications

    Search author on:PubMed Google Scholar

  4. Ralph W. Adams
    View author publications

    Search author on:PubMed Google Scholar

  5. George F. S. Whitehead
    View author publications

    Search author on:PubMed Google Scholar

  6. Avantika Hasija
    View author publications

    Search author on:PubMed Google Scholar

  7. David A. Leigh
    View author publications

    Search author on:PubMed Google Scholar

Contributions

H.-K.L. performed the synthesis and motor operations. B.M.W.R. and H.-K.L. performed kinetic analysis of the data. R.W.A. obtained deconstructed NMR spectra of the individual species in the catalytic cycle. G.F.S.W. and A.H. carried out the X-ray crystallography. S.B. and D.A.L. directed the research. The manuscript was prepared with contributions from all authors.

Corresponding author

Correspondence to David A. Leigh.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Chemistry thanks the anonymous reviewers for their contribution to the peer review of this work.

Additional information

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

Supplementary information

Supplementary Information (download PDF )

Supplementary Figs. 1–46, Discussion, Tables 1–12 and Spectra 1–55.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, HK., Roberts, B.M.W., Borsley, S. et al. Chiral catalysis-driven rotary molecular motors. Nat. Chem. (2026). https://doi.org/10.1038/s41557-025-02050-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Version of record:

  • DOI: https://doi.org/10.1038/s41557-025-02050-0

Search

Advanced 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