Abstract

The simultaneous synthesis of a molecular nine-crossing composite knot that contains three trefoil tangles of the same handedness and a \(9_7^3\) link (a type of cyclic [3]catenane topologically constrained to always have at least three twists within the links) is reported. Both compounds contain high degrees of topological writhe (w= 9), a structural feature of supercoiled DNA. The entwined products are generated from the cyclization of a hexameric Fe(ii) circular helicate by ring-closing olefin metathesis, with the mixture of topological isomers formed as a result of different ligand connectivity patterns. The metal-coordinated composite knot was isolated by crystallization, the topology unambiguously proven by tandem mass spectrometry, with X-ray crystallography confirming that the 324-atom loop crosses itself nine times with matching handedness (all Δ or all Λ) at every metal centre within each molecule. Controlling the connectivity of the ligand end groups on circular metal helicate scaffolds provides an effective synthetic strategy for the stereoselective synthesis of composite knots and other complex molecular topologies.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Additional information

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

References

  1. 1.

    Fenlon, E. E. Open problems in chemical topology. Eur. J. Org. Chem. 5023–5035 (2008).

  2. 2.

    Forgan, R. S., Sauvage, J.-P. & Stoddart, J. F. Chemical topology: complex molecular knots, links, and entanglements. Chem. Rev. 111, 5434–5464 (2011).

  3. 3.

    Lim, N. C. H. & Jackson, S. E. Molecular knots in biology and chemistry. J. Phys. Condens. Matter 27, 354101 (2015).

  4. 4.

    Fielden, S. D. P., Leigh, D. A. & Woltering, S. L. Molecular knots. Angew. Chem. Int. Ed. 56, 11166–11194 (2017).

  5. 5.

    Sauvage, J.-P. From chemical topology to molecular machines (Nobel lecture). Angew. Chem. Int. Ed. 56, 11080–11093 (2017).

  6. 6.

    Wasserman, S. A. & Cozzarelli, N. R. Biochemical topology: applications to DNA recombination and replication. Science 232, 951–960 (1986).

  7. 7.

    Vinograd, J. & Lebowitz, J. Physical and topological properties of circular DNA. J. Gen. Physiol. 49, 103–125 (1966).

  8. 8.

    Champoux, J. J. DNA topoisomerases: structure, function, and mechanism. Annu. Rev. Biochem. 70, 369–413 (2001).

  9. 9.

    Frank-Kamenetskii, M. D., Lukashin, A. V. & Vologodskii, A. V. Statistical mechanics and topology of polymer chains. Nature 258, 398–402 (1975).

  10. 10.

    Dzubiella, J. Sequence-specific size, structure, and stability of tight protein knots. Biophys. J. 96, 831–839 (2009).

  11. 11.

    Saitta, A. M., Soper, P. D., Wasserman, E. & Klein, M. L. Influence of a knot on the strength of a polymer strand. Nature 399, 46–48 (1999).

  12. 12.

    Sułkowska, J. I., Sułkowski, P., Szymczak, P. & Cieplak, M. Stabilizing effect of knots on proteins. Proc. Natl Acad. Sci. USA 105, 19714–19719 (2008).

  13. 13.

    Ziegler, F. et al. Knotting and unknotting of a protein in single molecule experiments. Proc. Natl Acad. Sci. USA 113, 7533–7538 (2016).

  14. 14.

    Micheletti, C., Marenduzzo, D. & Orlandini, E. Polymers with spatial or topological constraints: theoretical and computational results. Phys. Rep. 504, 1–73 (2011).

  15. 15.

    Adams, C. C. The Knot Book (American Mathematical Society, Providence, 2004).

  16. 16.

    Virnau, P., Kantor, Y. & Kardar, M. Knots in globule and coil phases of a model polyethylene. J. Am. Chem. Soc. 127, 15102–15106 (2005).

  17. 17.

    Rieger, F. C. & Virnau, P. A Monte Carlo study of knots in long double-stranded DNA chains. PLoS Comput. Biol. 12, e1005029 (2016).

  18. 18.

    Dietrich-Buchecker, C. O. & Sauvage, J.-P. A synthetic molecular trefoil knot. Angew. Chem. Int. Ed. 28, 189–192 (1989).

  19. 19.

    Ashton, P. R. et al. Molecular meccano 27—a template-directed synthesis of a molecular trefoil knot. Liebigs Ann. Recueil 2485–2494 (1997).

  20. 20.

    Guo, J., Mayers, P. C., Breault, G. A. & Hunter, C. A. Synthesis of a molecular trefoil knot by folding and closing on an octahedral coordination template. Nat. Chem. 2, 218–222 (2010).

  21. 21.

    Barran, P. E. et al. Active metal template synthesis of a molecular trefoil knot. Angew. Chem. Int. Ed. 50, 12280–12284 (2011).

  22. 22.

    Ayme, J.-F. et al. Synthetic molecular pentafoil knot. Nat. Chem. 4, 15–20 (2012).

  23. 23.

    Ayme, J.-F. et al. Lanthanide template synthesis of a molecular trefoil knot. J. Am. Chem. Soc. 136, 13142–13145 (2014).

  24. 24.

    Marcos, V. et al. Allosteric initiation and regulation of catalysis with a molecular knot. Science 352, 1555–1559 (2016).

  25. 25.

    Danon, J. J. et al. Braiding a molecular knot with eight crossings. Science 355, 159–162 (2017).

  26. 26.

    Zhang, L. et al. Molecular trefoil knot from a trimeric circular helicate. J. Am. Chem. Soc. 140, 4982–4985 (2018).

  27. 27.

    Safarowsky, O., Nieger, M., Fröhlich, R. & Vögtle, F. A molecular knot with twelve amide groups—one-step synthesis, crystal structure, chirality. Angew. Chem. Int. Ed. 39, 1616–1618 (2000).

  28. 28.

    Feigel, M., Ladberg, R., Engels, S., Herbst-Irmer, R. & Fröhlich, R. A trefoil knot made of amino acids and steroids. Angew. Chem. Int. Ed. 45, 5698–5702 (2006).

  29. 29.

    Ponnuswamy, N., Cougnon, F. B. L., Clough, J. M., Pantoş, G. D. & Sanders, J. K. M. Discovery of an organic trefoil knot. Science 338, 783–785 (2012).

  30. 30.

    Prakasam, T. et al. Simultaneous self-assembly of a [2]catenane, a trefoil knot, and a Solomon link from a simple pair of ligands. Angew. Chem. Int. Ed. 52, 9956–9960 (2013).

  31. 31.

    Ponnuswamy, N., Cougnon, F. B. L., Pantoş, G. D. & Sanders, J. K. M. Homochiral and meso figure eight knots and a Solomon link. J. Am. Chem. Soc. 136, 8243–8251 (2014).

  32. 32.

    Carina, R. F., Dietrich-Buchecker, C. & Sauvage, J.-P. Molecular composite knots. J. Am. Chem. Soc. 118, 9110–9116 (1996).

  33. 33.

    Ayme, J.-F., Beves, J. E., Campbell, C. J. & Leigh, D. A. Template synthesis of molecular knots. Chem. Soc. Rev. 42, 1700–1712 (2013).

  34. 34.

    Wood, C. S., Ronson, T. K., Belenguer, A. M., Holstein, J. J. & Nitschke, J. R. Two-stage directed self-assembly of a cyclic [3]catenane. Nat. Chem. 7, 354–358 (2015).

  35. 35.

    Leigh, D. A., Pritchard, R. G. & Stephens, A. J. A Star of David catenane. Nat. Chem. 6, 978–982 (2014).

  36. 36.

    Hasenknopf, B. et al. Self-assembly of tetra- and hexanuclear circular helicates. J. Am. Chem. Soc. 119, 10956–10962 (1997).

  37. 37.

    Garber, S. B., Kingsbury, J. S., Gray, B. L. & Hoveyda, A. H. Efficient and recyclable monomeric and dendritic Ru-based metathesis catalysts. J. Am. Chem. Soc. 122, 8168–8179 (2000).

  38. 38.

    Beves, J. E., Danon, J. J., Leigh, D. A., Lemonnier, J.-F. & Vitorica-Yrezabal, I. J. A Solomon link through an interwoven molecular grid. Angew. Chem. Int. Ed. 54, 7555–7559 (2015).

  39. 39.

    De Gennes, P. G. Reptation of a polymer chain in the presence of fixed obstacles. J. Chem. Phys. 55, 572–579 (1971).

  40. 40.

    Vetter, W. & Schill, G. Das Massenspektrum einer Catena-verbindung. Tetrahedron 23, 3079–3093 (1967).

  41. 41.

    Fujita, D. et al. Self-assembly of tetravalent Goldberg polyhedra from 144 small components. Nature 540, 563–566 (2016).

  42. 42.

    Fujita, D. et al. Self-assembly of M30L60 icosidodecahedron. Chem 1, 91–101 (2016).

  43. 43.

    Takata, M. The MEM/Rietveld method with nano-applications—accurate charge-density studies of nano-structured materials by synchrotron-radiation powder diffraction. Acta Cryst. A 64, 232–245 (2008).

  44. 44.

    Cerf, C. & Stasiak, A. A topological invariant to predict the three-dimensional writhe of ideal configurations of knots and links. Proc. Natl Acad. Sci. USA 97, 3795–3798 (2000).

  45. 45.

    Arsuga, J. et al. DNA knots reveal a chiral organization of DNA in phage capsids. Proc. Natl Acad. Sci. USA 102, 9165–9169 (2005).

  46. 46.

    Marenduzzo, D., Micheletti, C., Orlandini, E. & Sumners, D. W. Topological friction strongly affects viral DNA ejection. Proc. Natl Acad. Sci. USA 110, 20081–20086 (2013).

  47. 47.

    Clayden, J., Lund, A., Vallverdú, L. & Helliwell, M. Ultra-remote stereocontrol by conformational communication of information along a carbon chain. Nature 431, 966–971 (2004).

  48. 48.

    Alexander, J. W. & Briggs, G. B. On types of knotted curves. Ann. Math. 28, 562–586 (1926).

  49. 49.

    Menasco, W. & Thistlethwaite, M. The classification of alternating links. Ann. Math. 138, 113–171 (1993).

  50. 50.

    Chichak, K. S. et al. Molecular Borromean rings. Science 304, 1308–1312 (2004).

  51. 51.

    Thorp-Greenwood, F. L., Kulak, A. N. & Hardie, M. J. An infinite chainmail of M6L6 metallacycles featuring multiple Borromean links. Nat. Chem. 7, 526–531 (2015).

Download references

Acknowledgements

We thank the Engineering and Physical Sciences Research Council (EP/P027067/1) and the European Research Council (Advanced Grant no. 339019) for funding, the Diamond Light Source (UK) for synchrotron beam time on I19 (XR029), the University of Manchester for a President’s Doctoral Scholar Award (to L.Z.) and the Finnish Cultural Foundation for a postdoctoral grant (to P.J.). D.A.L. is a Royal Society Research Professor.

Author information

Author notes

  1. These authors contributed equally to this work: Liang Zhang, Alexander J. Stephens.

Affiliations

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

    • Liang Zhang
    • , Alexander J. Stephens
    • , Alina L. Nussbaumer
    • , Jean-François Lemonnier
    • , Pia Jurček
    • , Iñigo J. Vitorica-Yrezabal
    •  & David A. Leigh

Authors

  1. Search for Liang Zhang in:

  2. Search for Alexander J. Stephens in:

  3. Search for Alina L. Nussbaumer in:

  4. Search for Jean-François Lemonnier in:

  5. Search for Pia Jurček in:

  6. Search for Iñigo J. Vitorica-Yrezabal in:

  7. Search for David A. Leigh in:

Contributions

L.Z., A.J.S., A.L.N., J.-F.L. and P.J. carried out the synthesis and characterization studies. I.J.V.-Y. solved the crystal structure. D.A.L. directed the research. All the authors contributed to the analysis of the results and the writing of the manuscript.

Competing interests

The authors declare no competing interests.

Corresponding author

Correspondence to David A. Leigh.

Supplementary information

  1. Supplementary information

    Experimental methods, synthetic procedures and the characterization details for all new compounds, including the X-ray experimental details

  2. Crystallographic data

    CIF for compound [Fe62](PF6)12; CCDC reference: 1565130

  3. Supplementary Video

    A video file of the rotating X-ray crystal structure of the composite knot

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/s41557-018-0124-6

Further reading