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Autonomous fuelled directional rotation about a covalent single bond

Nature volume 604, pages 80–85 (2022)Cite this article

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Abstract

Biology operates through autonomous chemically fuelled molecular machinery1, including rotary motors such as adenosine triphosphate synthase2 and the bacterial flagellar motor3. Chemists have long sought to create analogous molecular structures with chemically powered, directionally rotating, components4,5,6,7,8,9,10,11,12,13,14,15,16,17. However, synthetic motor molecules capable of autonomous 360° directional rotation about a single bond have proved elusive, with previous designs lacking either autonomous fuelling7,10,12 or directionality6. Here we show that 1-phenylpyrrole 2,2′-dicarboxylic acid18,19 (1a) is a catalysis-driven20,21 motor that can continuously transduce energy from a chemical fuel9,20,21,22,23,24,25,26,27 to induce repetitive 360° directional rotation of the two aromatic rings around the covalent N–C bond that connects them. On treatment of 1a with a carbodiimide21,25,26,27, intramolecular anhydride formation between the rings and the anhydride’s hydrolysis both occur incessantly. Both reactions are kinetically gated28,29,30 causing directional bias. Accordingly, catalysis of carbodiimide hydration by the motor molecule continuously drives net directional rotation around the N–C bond. The directionality is determined by the handedness of both an additive that accelerates anhydride hydrolysis and that of the fuel, and is easily reversed additive31. More than 97% of fuel molecules are consumed through the chemical engine cycle24 with a directional bias of up to 71:29 with a chirality-matched fuel and additive. In other words, the motor makes a ‘mistake’ in direction every three to four turns. The 26-atom motor molecule’s simplicity augurs well for its structural optimization and the development of derivatives that can be interfaced with other components for the performance of work and tasks32,33,34,35,36.

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Fig. 1: Chemical engine cycle of an autonomous, continuously operating, chemically fuelled single bond rotary motor.
Fig. 2: Mechanical gating of 1-arylpyrrole 2,2′-dicarboxylic acids (1).
Fig. 3: Chemical transformations of 1-arylpyrrole 2,2′-dicarboxylic acids (1).
Fig. 4: Autonomous chemically fuelled operation of 1-arylpyrrole 2,2′-dicarboxylic acids (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 http://doi.org/10.17632/2zvst4kg2w.1.

References

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

    Article  ADS  CAS  PubMed  Google Scholar 

  2. Boyer, P. D. Energy, life, and ATP (Nobel lecture). Angew. Chem. Int. Ed. 37, 2296–2307 (1998).

    Article  Google Scholar 

  3. Santiveri, M. et al. Structure and function of stator units of the bacterial flagellar motor. Cell 183, 244–257 (2020).

    Article  CAS  PubMed  Google Scholar 

  4. Kelly, T. R., Tellitu, I. & Sestelo, J. P. In search of molecular ratchets. Angew. Chem. Int. Ed. Engl. 36, 1866–1868 (1997).

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  PubMed  Google Scholar 

  6. Mock, W. L. & Ochwat, K. J. Theory and example of a small-molecule motor. J. Phys. Org. Chem. 16, 175–182 (2003).

    Article  CAS  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).

    Article  ADS  CAS  PubMed  Google Scholar 

  8. 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  CAS  PubMed  Google Scholar 

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

    Article  ADS  CAS  PubMed  Google Scholar 

  10. 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 

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

    Article  ADS  CAS  PubMed  Google Scholar 

  12. 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 

  13. 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  ADS  CAS  PubMed  Google Scholar 

  14. Pooler, D. R. S., Lubbe, A. S., Crespi, S. & Feringa, B. L. Designing light-driven rotary molecular motors. Chem. Sci. 12, 14964–14986 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  16. Feynman, R. P., Leighton, R. B. & Sands, M. The Feynman Lectures on Physics Vol. 1, Ch. 46 (Addison-Wesley Publishing Company, 1963).

  17. Davis, A. P. Tilting at windmills? The second law survives. Angew. Chem. Int. Ed. 37, 909–910 (1998).

    Article  ADS  CAS  Google Scholar 

  18. Fogassy, K. et al. Efficient synthesis and resolution of (±)-1-[2-carboxy-6-(trifluoromethyl)phenyl]pyrrole-2-carboxylic acid. Tetrahedron Asymmetry 11, 4771–4780 (2000).

    Article  CAS  Google Scholar 

  19. Faigl, F., Tárkányi, G., Fogassy, K., Tepfenhardt, D. & Thurner, A. Synthesis and stereochemical stability of new atropisomeric 1-(substituted phenyl)pyrrole derivatives. Tetrahedron 64, 1371–1377 (2008).

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  PubMed  Google Scholar 

  21. 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).

    Article  CAS  PubMed  Google Scholar 

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

    Article  ADS  CAS  PubMed  Google Scholar 

  23. 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 

  24. 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  ADS  CAS  PubMed  Google Scholar 

  25. Tena-Solsona, M. et al. Non-equilibrium dissipative supramolecular materials with a tunable lifetime. Nat. Commun. 8, 15895 (2017).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  26. 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  CAS  PubMed  Google Scholar 

  27. Bal, S., Das, K., Ahmed, S. & Das, D. Chemically fueled dissipative self-assembly that exploits cooperative catalysis. Angew. Chem. Int. Ed. 58, 244–247 (2019).

    Article  CAS  Google Scholar 

  28. 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  ADS  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Astumian, R. D., Mukherjee, S. & Warshel, A. The physics and physical chemistry of molecular machines. ChemPhysChem 17, 1719–1741 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Dálaigh, C. Ó. & Connon, S. J. Nonenzymatic acylative kinetic resolution of Baylis-Hillman adducts. J. Org. Chem. 72, 7066–7069 (2007).

    Article  PubMed  Google Scholar 

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

    Article  ADS  PubMed  Google Scholar 

  33. García-López, V. et al. Molecular machines open cell membranes. Nature 548, 567–572 (2017).

    Article  ADS  PubMed  Google Scholar 

  34. Feng, L. et al. Active mechanisorption driven by pumping cassettes. Science 374, 1215–1221 (2021).

    Article  ADS  CAS  PubMed  Google Scholar 

  35. Thomas, D., et al. Pumping between phases with a pulsed-fuel molecular ratchet. Preprint at https://doi.org/10.33774/chemrxiv-2021-fl7tv (2021).

  36. Zhang, Q. et al. Muscle-like artificial molecular actuators for nanoparticles. Chem 4, 2670–2684 (2018).

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  38. Astumian, R. D. Thermodynamics and kinetics of a Brownian Motor. Science 276, 917–922 (1997).

    Article  CAS  PubMed  Google Scholar 

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

    Article  ADS  CAS  PubMed  Google Scholar 

  40. Alvarez-Pérez, M., Goldup, S. M., Leigh, D. A. & Slawin, A. M. Z. A chemically-driven molecular information ratchet. J. Am. Chem. Soc. 130, 1836–1838 (2008).

    Article  PubMed  Google Scholar 

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

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  42. Jayalath, I. M., Wang, H., Mantel, G., Kariyawasam, L. S. & Hartley, C. S. Chemically fueled transient geometry changes in diphenic acids. Org. Lett. 22, 7567–7571 (2020).

    Article  CAS  PubMed  Google Scholar 

  43. Jayalath, I. M., Gerken, M. M., Mantel, G. & Hartley, C. S. Substituent effects on transient, carbodiimide-induced geometry changes in diphenic acids. J. Org. Chem. 86, 12024–12033 (2021).

    Article  CAS  PubMed  Google Scholar 

  44. Amano, S. et al. Insights from an information thermodynamics analysis of a synthetic molecular motor. Nat. Chem. (2022) https://doi.org/10.1038/s41557-022-00899-z.

  45. Ma, B. & Nussinov, R. Enzyme dynamics point to stepwise conformational selection in catalysis. Curr. Opin. Chem. Biol. 14, 652–659 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Kamerlin, S. C. & Warshel, A. At the dawn of the 21st century: is dynamics the missing link for understanding enzyme catalysis? Proteins 78, 1339–1375 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Krajnik, B. et al. Defocused imaging of UV-driven surface-bound molecular motors. J. Am. Chem. Soc. 139, 7156–7159 (2017).

    Article  CAS  PubMed  Google Scholar 

  48. Roke, D., Wezenberg, S. J. & Feringa, B. L. Molecular rotary motors: unidirectional motion around double bonds. Proc. Natl. Acad. Sci. USA 115, 9423–9431 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank the Engineering and Physical Sciences Research Council (EPSRC; grant number EP/P027067/1), the European Research Council (ERC; Advanced Grant number 786630) and the German Research Foundation (DFG; Individual Postdoctoral Fellowship to E.K.) for funding, the University of Manchester’s Department of Chemistry Services for mass spectrometry, I. J. Vitorica-Yrezabal for X-ray crystallography used to assign atropisomer handedness, S. Amano and J. M. Gallagher for useful discussions, and S. Jantzen of Biocinematics for the rotary motor animation. D.A.L. is a Royal Society Research Professor.

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Author notes

  1. These authors contributed equally: Stefan Borsley, Elisabeth Kreidt, Benjamin M. W. Roberts

Authors and Affiliations

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

    Stefan Borsley, Elisabeth Kreidt, David A. Leigh & Benjamin M. W. Roberts

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

    David A. Leigh

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Contributions

S.B., E.K. and B.M.W.R. designed and carried out the experiments. D.A.L. directed the research. All authors contributed to the analysis of the results and the writing of the manuscript.

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Correspondence to David A. Leigh.

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Supplementary Information

Supplementary sections 1–7 and Appendix

Supplementary Video 1

Animation of the design and autonomous chemically fuelled rotation of motor molecule 1a. Credit: Stuart Jantzen, Biocinematics.

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Borsley, S., Kreidt, E., Leigh, D.A. et al. Autonomous fuelled directional rotation about a covalent single bond. Nature 604, 80–85 (2022). https://doi.org/10.1038/s41586-022-04450-5

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