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.
Subscription info for Chinese customers
We have a dedicated website for our Chinese customers. Please go to naturechina.com to subscribe to this journal.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Skou, J. C. The identification of the sodium–potassium pump (Nobel Lecture). Angew. Chem. Int. Ed. 37, 2320–2328 (1998).
Lodish, H. et al. Transport across cell membranes. In Molecular Cell Biology Vol. 4, Ch. 15 (W. H. Freeman, 2000).
Du, D. et al. Multidrug efflux pumps: structure, function and regulation. Nat. Rev. Microbiol. 16, 523–539 (2018).
Qiu, Y., Feng, Y., Guo, Q.-H., Astumian, R. D. & Stoddart, J. F. Pumps through the ages. Chem 6, 1952–1977 (2020).
Steinberg-Yfrach, G. et al. Conversion of light energy to proton potential in liposomes by artificial photosynthetic reaction centres. Nature 385, 239–241 (1997).
Bennett, I. M. et al. Active transport of Ca2+ by an artificial photosynthetic membrane. Nature 420, 398–401 (2002).
Bhosale, S. et al. Photoproduction of proton gradients with π-stacked fluorophore scaffolds in lipid bilayers. Science 313, 84–86 (2006).
Serreli, V., Lee, C.-F., Kay, E. R. & Leigh, D. A. A molecular information ratchet. Nature 445, 523–527 (2007).
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).
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).
Cheng, C. et al. An artificial molecular pump. Nat. Nanotechnol. 10, 547–553 (2015).
Pezzato, C. et al. An efficient artificial molecular pump. Tetrahedron 73, 4849–4857 (2017).
Erbas-Cakmak, S. et al. Rotary and linear molecular motors driven by pulses of a chemical fuel. Science 358, 340–343 (2017).
Pezzato, C. et al. Controlling dual molecular pumps electrochemically. Angew. Chem. Int. Ed. 57, 9325–9329 (2018).
Qiu, Y. et al. A molecular dual pump. J. Am. Chem. Soc. 141, 17472–17476 (2019).
Qiu, Y. et al. A precise polyrotaxane synthesizer. Science 368, 1247–1253 (2020).
Astumian, R. D. & Bier, M. Mechanochemical coupling of the motion of molecular motors to ATP hydrolysis. Biophys. J. 70, 637–653 (1996).
Kay, E. R., Leigh, D. A. & Zerbetto, F. Synthetic molecular motors and mechanical machines. Angew. Chem. Int. Ed. 46, 72–191 (2007).
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).
Astumian, R. D. Kinetic asymmetry allows macromolecular catalysts to drive an information ratchet. Nat. Commun. 10, 3837 (2019).
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).
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).
Kassem, S. et al. Artificial molecular motors. Chem. Soc. Rev. 46, 2592–2621 (2017).
Wang, Q., Chen, D. & Tian, H. Artificial molecular machines that can perform work. Sci. China Chem. 61, 1261–1273 (2018).
Findlay, J. A. & Crowley, J. D. Functional nanomachines: recent advances in synthetic molecular machinery. Tetrahedron Lett. 59, 334–346 (2018).
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).
Zheng, H. et al. A dual‐response rotaxane based on a 1,2,3‐triazole ring as a novel recognition station. Chem. Eur. J. 15, 13253–13262 (2009).
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).
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).
Tian, C., Fielden, S. D. P., Pérez-Saavedra, B., Vitorica-Yrezabal, I. J. & Leigh, D. A. Single-step enantioselective synthesis of mechanically planar chiral rotaxanes using a chiral leaving group strategy. J. Am. Chem. Soc. 142, 9803–9808 (2020).
Denis, M. & Goldup, S. M. The active template approach to interlocked molecules: Principles, progress and applications. Nat. Rev. Chem. 1, 0061 (2017).
Wilson, M. R. et al. An autonomous chemically fuelled small-molecule motor. Nature 534, 235–240 (2016).
Fyfe, M. C. T. et al. Anion assisted self-assembly. Angew. Chem. Int. Ed. Engl. 36, 2068–2070 (1997).
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).
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).
Ragazzon, G. & Prins, L. J. Energy consumption in chemical fuel-driven self-assembly. Nat. Nanotechnol. 13, 882–889 (2018).
Rieß, B., Grötsch, R. & Boekhoven, J. The design of dissipative molecular assemblies driven by chemical reaction cycles. Chem 6, 552–578 (2020).
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).
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).
Howard, J. Protein power strokes. Curr. Biol. 16, R517–R519 (2006).
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).
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).
Zhang, L., Marcos, V. & Leigh, D. A. Molecular machines with bio-inspired mechanisms. Proc. Natl Acad. Sci. USA 115, 9397–9404 (2018).
Biagini, C. et al. Dissipative catalysis with a molecular machine. Angew. Chem. Int. Ed. 58, 9876–9880 (2019).
Astumian, R. D. et al. Non-equilibrium kinetics and trajectory thermodynamics of synthetic molecular pumps. Mater. Chem. 4, 1304–1314 (2020).
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).
Aprahamian, I. The future of molecular machines. ACS Cent. Sci. 6, 347–358 (2020).
Moulin, E., Faour, L., Carmona-Vargas, C. C. & Giuseppone, N. From molecular machines to stimuli-responsive materials. Adv. Mater. 32, 1906036 (2020).
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.
The authors declare no competing interests.
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.
About this article
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
Nature Nanotechnology (2021)