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Stereoselective synthesis of a composite knot with nine crossings

Nature Chemistry volume 10, pages 1083–1088 (2018)Cite this article

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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.

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Fig. 1: Topologies that result from joining ligand strands with the terminal binding sites coordinated to neighbouring metal ions in a hexameric circular helicate.
Fig. 2: The 12 component (6 × ligand 1; 6 × Fe2+) assembly of the intermediate hexameric circular helicate [Fe616](PF6)12 and the synthesis of the +31#+31#+31 composite knot 2 and \({\mathbf{9}}_{\mathbf{7}}^{\mathbf{3}}\) link 3.
Fig. 3: 1H NMR spectra (600 MHz, 298 K) of molecular knot 2, link 3, building block 1 and their coordination complexes.
Fig. 4: ESI–MS and MS/MS experiments on molecular knot 2 and link 3.
Fig. 5: A 1.8 Å resolution X-ray crystal structure of the +31#+31#+31 composite knot [Fe62](PF6)12, in which parts of the molecule are well resolved (for example, the metal ions and much of the circular helicate), whereas others (in particular the flexible linker chains) needed to be modelled to fit the electron density map in a manner analogous to protein crystallography.

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References

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

    Article  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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).

    Article  CAS  PubMed  Google Scholar 

  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).

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

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

  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).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  Google Scholar 

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

    Article  Google Scholar 

  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).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  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).

    Article  CAS  PubMed  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  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).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  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).

    Article  CAS  PubMed  Google Scholar 

  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).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  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).

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  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).

    Article  CAS  PubMed  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  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).

    Article  CAS  PubMed  Google Scholar 

  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).

    Article  CAS  PubMed  Google Scholar 

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

    Article  Google Scholar 

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

    Article  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  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).

    Article  CAS  PubMed  Google Scholar 

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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.

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

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  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

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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.

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Correspondence to David A. Leigh.

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Supplementary information

Supplementary information

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

Crystallographic data

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

Supplementary Video

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

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Zhang, L., Stephens, A.J., Nussbaumer, A.L. et al. Stereoselective synthesis of a composite knot with nine crossings. Nature Chem 10, 1083–1088 (2018). https://doi.org/10.1038/s41557-018-0124-6

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