Catenanes—molecules comprising two interlocking rings held together like links in a chain—are topologically non-trivial: a catenane is a topological isomer of its separated rings, but the rings cannot be disconnected without bond scission. Catenanes can exist as topological enantiomers if both rings have directionality conferred by a defined atom sequence, but this has led to the assumption that the stereochemistry of chiral catenanes composed of oriented rings is inherently topological in nature. Here we show that this assumption is incorrect by synthesizing an example that contains the same fundamental stereogenic unit but whose stereochemistry is Euclidean. One ring in this chiral catenane is oriented by the geometry of an exocyclic double rather than determined by atom sequence within the ring. Isomerization of the exocyclic double bond results in racemization of the catenane, confirming that the stereochemistry is not topological in nature. Thus, we can unite the stereochemistry of catenanes with that of their topologically trivial cousins, the rotaxanes, enabling a more unified approach to their discussion.
This is a preview of subscription content, access via your institution
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Rent or buy this article
Prices vary by article type
Prices may be subject to local taxes which are calculated during checkout
Raw characterization data are available through the University of Southampton data repository (https://doi.org/10.5258/SOTON/D2492)40. Crystallographic data for the structures reported in this Article have been deposited at the Cambridge Crystallographic Data Centre, under deposition numbers CCDC 2207578 ((S,Smp,Eco-c)-4) and CCDC 2207579 (S34). Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/.
Walba, D. M. Topological stereochemistry. Tetrahedron 41, 3161–3212 (1985).
Flapan, E. When Topology Meets Chemistry (Cambridge Univ. Press, 2012).
Cayley, E. Ueber die analytischen Figuren, welche in der Mathematik Bäume genannt werden und ihre Anwendung auf die Theorie chemischer Verbindungen. Ber. Dtsch. Chem. Ges. 8, 1056–1059 (2006).
Devillers, J. & Balaban, A. T. Topological Indices and Related Descriptors in QSAR and QSPR (CRC Press, 2000).
Thomson, W. II. On vortex atoms. Philos. Mag. 34, 15–24 (1867).
Mislow, K. On the classification of pairwise relations between isomeric structures. Bull. Soc. Chim. Belg. 86, 595–601 (2010).
Frisch, H. L. & Wasserman, E. Chemical topology. J. Am. Chem. Soc. 83, 3789–3795 (1961).
Wasserman, E. The preparation of interlocking rings: a catenane. J. Am. Chem. Soc. 82, 4433–4434 (1960).
Herges, R. Topology in chemistry: designing Möbius molecules. Chem. Rev. 106, 4820–4842 (2006).
Ajami, D., Oeckler, O., Simon, A. & Herges, R. Synthesis of a Möbius aromatic hydrocarbon. Nature 426, 819–821 (2003).
Segawa, Y. et al. Synthesis of a Möbius carbon nanobelt. Nat. Synth. 1, 535–541 (2022).
Fielden, S. D. P., Leigh, D. A. & Woltering, S. L. Molecular knots. Angew. Chem. Int. Ed. 56, 11166–11194 (2017).
Paquette, L. A. & Vazeux, M. Threefold transannular epoxide cyclization. Synthesis of a heterocyclic 17-hexaquinane. Tetrahedron Lett. 22, 291–294 (1981).
Benner, S. A., Maggio, J. E. & Simmons, H. E. Rearrangement of a geometrically restricted triepoxide to the first topologically nonplanar molecule: a reaction path elucidated by using oxygen isotope effects on carbon-13 chemical shifts. J. Am. Chem. Soc. 103, 1581–1582 (1981).
Dabrowski-Tumanski, P. & Sulkowska, J. I. Topological knots and links in proteins. Proc. Natl Acad. Sci. USA 114, 3415–3420 (2017).
Bettotti, P. et al. Structure and properties of DNA molecules over the full range of biologically relevant supercoiling states. Sci. Rep. 8, 6163 (2018).
Chambron, J. C., Dietrich-Buchecker, C., Rapenne, G. & Sauvage, J. P. Resolution of topologically chiral molecular objects. Chirality 10, 125–133 (1998).
Yamamoto, C., Okamoto, Y., Schmidt, T., Jager, R. & Vogtle, F. Enantiomeric resolution of cycloenantiomeric rotaxane, topologically chiral catenane, and pretzel-shaped molecules: observation of pronounced circular dichroism. J. Am. Chem. Soc. 119, 10547–10548 (1997).
Walba, D. M., Zheng, Q. Y. & Schilling, K. Topological stereochemistry. 8. Experimental studies on the hook and ladder approach to molecular knots: synthesis of a topologically chiral cyclized hook and ladder. J. Am. Chem. Soc. 114, 6259–6260 (1992).
Zhang, G. et al. Lanthanide template synthesis of trefoil knots of single handedness. J. Am. Chem. Soc. 137, 10437–10442 (2015).
Carpenter, J. P. et al. Controlling the shape and chirality of an eight-crossing molecular knot. Chem 7, 1534–1543 (2021).
Ponnuswamy, N., Cougnon, F. B., Pantos, G. D. & Sanders, J. K. Homochiral and meso figure eight knots and a Solomon link. J. Am. Chem. Soc. 136, 8243–8251 (2014).
Cui, Z., Lu, Y., Gao, X., Feng, H.-J. & Jin, G.-X. Stereoselective synthesis of a topologically chiral Solomon link. J. Am. Chem. Soc. 142, 13667–13671 (2020).
Jamieson, E. M. G., Modicom, F. & Goldup, S. M. Chirality in rotaxanes and catenanes. Chem. Soc. Rev. 47, 5266–5311 (2018).
Maynard, J. R. J. & Goldup, S. M. Strategies for the synthesis of enantiopure mechanically chiral molecules. Chem 6, 1914–1932 (2020).
Wang, Y. et al. Multistate circularly polarized luminescence switching through stimuli‐induced co‐conformation regulations of pyrene‐functionalized topologically chiral catenane. Angew. Chem. Int. Ed. 61, e202210542 (2022).
Denis, M., Lewis, J. E. M., Modicom, F. & Goldup, S. M. An auxiliary approach for the stereoselective synthesis of topologically chiral catenanes. Chem 5, 1512–1520 (2019).
Denis, M. & Goldup, S. M. The active template approach to interlocked molecules. Nat. Rev. Chem. 1, 0061 (2017).
Zhang, S., Rodríguez-Rubio, A., Saady, A., Tizzard, G. J. & Goldup, S. M. A chiral macrocycle for the stereoselective synthesis of mechanically planar chiral rotaxanes and catenanes. Chem (in the press); https://doi.org/10.1016/j.chempr.2023.01.009
Corra, S., de Vet, C., Baroncini, M., Credi, A. & Silvi, S. Stereodynamics of E/Z isomerization in rotaxanes through mechanical shuttling and covalent bond rotation. Chem 7, 2137–2150 (2021).
Rodriguez-Rubio, A., Savoini, A., Modicom, F., Butler, P. & Goldup, S. M. A co-conformationally ‘topologically’ chiral catenane. J. Am. Chem. Soc. 144, 11927–11932 (2022).
Maynard, J. R. J., Gallagher, P., Lozano, D., Butler, P. & Goldup, S. M. Mechanically axially chiral catenanes and noncanonical mechanically axially chiral rotaxanes. Nat. Chem. 14, 1038–1044 (2022).
Caprice, K. et al. Diastereoselective amplification of a mechanically chiral catenane. J. Am. Chem. Soc. 143, 11957–11962 (2021).
Canfield, P. J. et al. A new fundamental type of conformational isomerism. Nat. Chem. 10, 615–624 (2018).
Reisberg, S. H. et al. Total synthesis reveals atypical atropisomerism in a small-molecule natural product, tryptorubin A. Science 367, 458–463 (2020).
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).
Mo, K. et al. Intrinsically unidirectional chemically fuelled rotary molecular motors. Nature 609, 293–298 (2022).
Cahn, R. S., Ingold, C. & Prelog, V. Specification of molecular chirality. Angew. Chem. Int. Ed. 5, 385–415 (1966).
Alvarez-Perez, M., Goldup, S. M., Leigh, D. A. & Slawin, A. M. A chemically-driven molecular information ratchet. J. Am. Chem. Soc. 130, 1836–1838 (2008).
Pairault, N. et al. Dataset supporting the article ‘A catenane that is topologically achiral despite being composed of oriented rings’. University of Southampton Institutional Research Repository https://doi.org/10.5258/SOTON/D2492 (2023).
S.M.G thanks the European Research Council (Consolidator Grant, agreement no. 724987) and the Royal Society for a Research Fellowship (RSWF\FT\180010). E.M.G.J. thanks the EPSRC and University of Southampton for a Doctoral Prize Fellowship.
The authors declare no competing interests.
Peer review information
Nature Chemistry thanks the anonymous reviewers for their contribution to the peer review of this work.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Extended Data Fig. 1 Annotated representations of catenane 3 for assigning the absolute stereochemistry of the molecule.
a. The structure of catenane (S,Rmp,Eco-c)-3 produced from the reaction of (Z)-1 and (S)-2. The triazole C atom in bold is higher priority for the purpose of defining the co-conformational geometry. b. The (S,Rmp,Zco-c)-3 co-conformational covalent geometric isomer of 3. The triazole C atom in bold is higher priority for the purpose of defining the co-conformational geometry in this structure. c. The components of 3 with atoms A and B labelled. The triazole C atom in bold is higher priority for the purpose of defining the orientation of the triazole containing macrocycle (this is a fixed property of the covalent structure, as opposed to the bold atoms in a. and b. which depend on the position of the bipyridine ring). d. Catenane 3 redrawn such that the A→B vector of the bipyridine macrocycle passes through the triazole macrocycle away from the observer, confirming that the stereochemistry of 3 produced from (S)-2 is Rmp.
Extended Data Fig. 2 Annotated representations of catenane 4 for assigning the absolute stereochemistry of the molecule.
a. The structure of catenane (S,Smp,Eco-c)-4 produced from (S)-2. b. The bipyridine macrocycle with atoms A and B labelled (A and B atoms of the triazole macrocycle as in Extended Data Fig. 1c). c. Catenane 4 with the A→B vector of the bipyridine ring passing through the triazole macrocycle away from the observer, confirming that the stereochemistry of 4 produced from (S)-2 is Smp.
Extended Data Fig. 3 Annotated representations of catenane S16 for assigning the absolute stereochemistry of the molecule.
a. The structure of catenane (Smp,Eco-c)-S16 produced from (S)-2. b. The bipyridine macrocycle of S16 with atoms A and B labelled (A and B atoms of the triazole macrocycle as in Extended Data Fig. 1c). c. Catenane S16 with the A→B vector of the bipyridine macrocycle passing through the triazole macrocycle away from the observer, confirming that the stereochemistry of S16 produced from (S)-2 is Smp.
Extended Data Fig. 4 Annotated representations of catenane 5 for assigning the absolute stereochemistry of the molecule.
a. The structure of catenane (Rmp,Eco-c)-5 produced from (S)-2 as depicted in the manuscript. b. The triazole-containing macrocycle with atoms A and B labelled (A and B atoms of the bipyridine macrocycle as in Extended Data Fig. 3b). c. Catenane 5 with the A→B vector of the bipyridine macrocycle passing through the triazole macrocycle away from the observer, confirming that the stereochemistry of 5 produced from (S)-2 is Rmp.
About this article
Cite this article
Pairault, N., Rizzi, F., Lozano, D. et al. A catenane that is topologically achiral despite being composed of oriented rings. Nat. Chem. 15, 781–786 (2023). https://doi.org/10.1038/s41557-023-01194-1