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Electron-catalysed molecular recognition


Molecular recognition1,2,3,4 and supramolecular assembly5,6,7,8 cover a broad spectrum9,10,11 of non-covalently orchestrated phenomena between molecules. Catalysis12 of such processes, however, unlike that for the formation of covalent bonds, is limited to approaches13,14,15,16 that rely on sophisticated catalyst design. Here we establish a simple and versatile strategy to facilitate molecular recognition by extending electron catalysis17, which is widely applied18,19,20,21 in synthetic covalent chemistry, into the realm of supramolecular non-covalent chemistry. As a proof of principle, we show that the formation of a trisradical complex22 between a macrocyclic host and a dumbbell-shaped guest—a molecular recognition process that is kinetically forbidden under ambient conditions—can be accelerated substantially on the addition of catalytic amounts of a chemical electron source. It is, therefore, electrochemically possible to control23 the molecular recognition temporally and produce a nearly arbitrary molar ratio between the substrates and complexes ranging between zero and the equilibrium value. Such kinetically stable supramolecular systems24 are difficult to obtain precisely by other means. The use of the electron as a catalyst in molecular recognition will inspire chemists and biologists to explore strategies that can be used to fine-tune non-covalent events, control assembly at different length scales25,26,27 and ultimately create new forms of complex matter28,29,30.

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Fig. 1: Design of an electron-catalysed molecular recognition process.
Fig. 2: Molecular recognition accelerated by catalytic amounts of cobaltocene (CoCp2).
Fig. 3: Detection and verification of the key intermediate in the electron-catalysed molecular recognition process.
Fig. 4: Electrochemically controlled molecular recognition.

Data availability

The data that support the findings of this study are available within the paper and its Supplementary Information files.


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We thank Northwestern University (NU) for its continued support of this research and acknowledge the Integrated Molecular Structure Education and Research Center (IMSERC) at NU for providing access to equipment for relevant experiments. The computational investigations at California Institute of Technology were supported by National Science Foundation grant no. CBET-2005250 (W.-G.L. and W.A.G.). This work was also supported by the Department of Energy, Office of Science, Office of Basic Energy Sciences under Award DE-FG02-99ER14999 (M.R.W.) and the Natural Science Foundation of Anhui Province grant no. 2108085MB31 (D.S.).

Author information

Authors and Affiliations



Y.J., Y.Q. and J.F.S. conceived the idea for this project. L.Z. proposed a key mechanistic conjecture. W.-G.L. and W.A.G. performed quantum mechanical calculations. Y.J. and Y.Q. synthesized and characterized the materials with the help of H.C., Y.F., K.C., D.S., B.S., X.-Y.C., X.L. and X.Z. H.M., R.M.Y. and M.R.W. performed the electron paramagnetic resonance characterizations and detailed analyses. C.L.S. performed the single-crystal X-ray diffraction. R.D.A. contributed to the theoretical analyses on the mechanism of electron catalysis. Y.J., Y.Q. and J.F.S. wrote the first and second drafts of the paper. J.F.S. and W.A.G. directed the project. All the authors participated in evaluating the results and commented on the manuscript.

Corresponding authors

Correspondence to William A. Goddard III or J. Fraser Stoddart.

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Competing interests

Y.J., Y.Q. and J.F.S. have filed a patent application lodged with Northwestern University (INVO reference no. NU 2021-248) based on this work.

Peer review

Peer review information

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

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Extended data figures and tables

Extended Data Fig. 1 The electron as an efficient catalyst for both covalent reactions and molecular recognition.

a, Electron-catalysed covalent reactions are well established in synthetic covalent chemistry, particularly for radical-mediated photoredox catalysis and organic electrosynthesis. Consider a reaction A + BA–B, where a high energy barrier causes the reaction to be very slow. Injection of an electron reduces one of the substrates (A) to a highly reactive radical species (A•−), which can rapidly form a covalent bond with the other substrate (B). The resulting intermediate (A•−–B) releases the electron to afford the final product (A–B). Whereas the overall process is redox neutral, i.e., the redox state remains the same during the transformation from the substrates to product, the catalytic pathway, which involves the temporary addition of an electron, leads to a substantially lower energy barrier, thereby expediting the formation of the covalent bond. In this process, the electron has acted as an effective catalyst. b, The research reported in this article aims to extend the paradigm of electron catalysis to promoting and controlling molecular recognition. The trajectory for this noncovalent process is similar to that for electron-catalysed covalent reactions, except that the product is a supramolecular complex wherein molecular components are assembled courtesy of noncovalent bonding interaction(s), rather than a molecule whose atoms are connected by covalent bond(s).

Supplementary information

Supplementary Information

Supplementary Figs. 1–45, Schemes 1–9, Tables 1–8, supplementary text and notes, extensive experimental data, quantum mechanical calculation results and detailed discussions.

Supplementary Data

The crystallographic data for the [2]catenane in its bisradical dicationic state, which is available free of charge from the Cambridge Crystallographic Data Centre. The CCDC number is 2125118.

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Jiao, Y., Qiu, Y., Zhang, L. et al. Electron-catalysed molecular recognition. Nature 603, 265–270 (2022).

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