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Controlled folding of synthetic polymer chains through the formation of positionable covalent bridges


Covalent bridges play a crucial role in the folding process of sequence-defined biopolymers. This feature, however, has not been recreated in synthetic polymers because, apart from some simple regular arrangements (such as block co-polymers), these macromolecules generally do not exhibit a controlled primary structure—that is, it is difficult to predetermine precisely the sequence of their monomers. Herein, we introduce a versatile strategy for preparing foldable linear polymer chains. Well-defined polymers were synthesized by the atom transfer radical polymerization of styrene. The controlled addition of discrete amounts of protected maleimide at precise times during the synthesis enabled the formation of polystyrene chains that contained positionable reactive alkyne functions. Intramolecular reactions between these functions subsequently led to the formation of different types of covalently folded polymer chains. For example, tadpole (P-shaped), pseudocyclic (Q-shaped), bicyclic (8-shaped) and knotted (α-shaped) macromolecular origamis were prepared in a relatively straightforward manner.

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Figure 1: Covalent folding of linear synthetic polymer chains.
Figure 2: Characterization of the covalent folding process.


  1. 1

    Anfinsen, C. B. Principles that govern the folding of protein chains. Science 181, 223–230 (1973).

    CAS  Article  Google Scholar 

  2. 2

    Dobson, C. M. Protein folding and misfolding. Nature 426, 884–890 (2003).

    CAS  Article  Google Scholar 

  3. 3

    Flory, P. J. & Yoon, D. Y. Molecular morphology in semicrystalline polymers. Nature 272, 226–229 (1978).

    CAS  Article  Google Scholar 

  4. 4

    Sadler, D. M. New explanation for chain folding in polymers. Nature 326, 174–177 (1987).

    CAS  Article  Google Scholar 

  5. 5

    Gellman, S. H. Foldamers: a manifesto. Acc. Chem. Res. 31, 173–180 (1998).

    CAS  Article  Google Scholar 

  6. 6

    Hill, D. J., Mio, M. J., Prince, R. B., Hughes, T. S. & Moore, J. S. A field guide to foldamers. Chem. Rev. 101, 3893–4011 (2001).

    CAS  Article  Google Scholar 

  7. 7

    Huc, I. Aromatic oligoamide foldamers. Eur. J. Org. Chem. 17–29 (2004).

  8. 8

    Yashima, E., Maeda, K., Iida, H., Furusho, Y. & Nagai, K. Helical polymers: synthesis, structures, and functions. Chem. Rev. 109, 6102–6211 (2009).

    CAS  Article  Google Scholar 

  9. 9

    Miwa, K., Furusho, Y. & Yashima, E. Ion-triggered spring-like motion of a double helicate accompanied by anisotropic twisting. Nature Chem. 2, 444–449 (2010).

    CAS  Article  Google Scholar 

  10. 10

    Badi, N. & Lutz, J.-F. Sequence control in polymer synthesis. Chem. Soc. Rev. 38, 3383–3390 (2009).

    CAS  Article  Google Scholar 

  11. 11

    Lutz, J.-F. Polymer chemistry: a controlled sequence of events. Nature Chem. 2, 84–85 (2010).

    CAS  Article  Google Scholar 

  12. 12

    Lutz, J.-F. Sequence-controlled polymerizations: the next Holy Grail in polymer science? Polym. Chem. 1, 55–62 (2010).

    CAS  Article  Google Scholar 

  13. 13

    van Gorp, J. J., Vekemans, J. & Meijer, E. W. Facile synthesis of a chiral polymeric helix; folding by intramolecular hydrogen bonding. Chem. Commun. 60–61 (2004).

  14. 14

    Meudtner, R. M. & Hecht, S. Responsive backbones based on alternating triazole–pyridine/benzene copolymers: from helically folding polymers to metallosupramolecularly crosslinked gels. Macromol. Rapid Commun. 29, 347–351 (2008).

    CAS  Article  Google Scholar 

  15. 15

    Yu, T. B., Bai, J. Z. & Guan, Z. B. Cycloaddition-promoted self-assembly of a polymer into well-defined beta sheets and hierarchical nanofibrils. Angew. Chem. Int. Ed. 48, 1097–1101 (2009).

    CAS  Article  Google Scholar 

  16. 16

    Harth, E. et al. A facile approach to architecturally defined nanoparticles via intramolecular chain collapse. J. Am. Chem. Soc. 124, 8653–8660 (2002).

    CAS  Article  Google Scholar 

  17. 17

    Foster, E. J., Berda, E. B. & Meijer, E. W. Metastable supramolecular polymer nanoparticles via intramolecular collapse of single polymer chains. J. Am. Chem. Soc. 131, 6964–6966 (2009).

    CAS  Article  Google Scholar 

  18. 18

    Berda, E. B., Foster, E. J. & Meijer, E. W. Toward controlling folding in synthetic polymers: fabricating and characterizing supramolecular single-chain nanoparticles. Macromolecules 43, 1430–1437 (2010).

    CAS  Article  Google Scholar 

  19. 19

    Grayson, S. M. Macromolecular chemistry: polymers kept in the loop. Nature Chem. 1, 178–179 (2009).

    CAS  Article  Google Scholar 

  20. 20

    Laurent, B. A. & Grayson, S. M. An efficient route to well-defined macrocyclic polymers via ‘click’ cyclization. J. Am. Chem. Soc. 128, 4238–4239 (2006).

    CAS  Article  Google Scholar 

  21. 21

    Schappacher, M. & Deffieux, A. Synthesis of macrocyclic copolymer brushes and their self-assembly into supramolecular tubes. Science 319, 1512–1515 (2008).

    CAS  Article  Google Scholar 

  22. 22

    Tezuka, Y. & Oike, H. Topological polymer chemistry. Prog. Polym. Sci. 27, 1069–1122 (2002).

    CAS  Article  Google Scholar 

  23. 23

    Lonsdale, D. E. & Monteiro, M. J. Various polystyrene topologies built from tailored cyclic polystyrene via CuAAC reactions. Chem. Commun. 7945–7947 (2010).

  24. 24

    Pfeifer, S. & Lutz, J.-F. A facile procedure for controlling monomer sequence distribution in radical chain polymerizations. J. Am. Chem. Soc. 129, 9542–9543 (2007).

    CAS  Article  Google Scholar 

  25. 25

    Pfeifer, S. & Lutz, J.-F. Development of a library of N-substituted maleimides for the local functionalization of linear polymer chains. Chem. Eur. J. 14, 10949–10957 (2008).

    CAS  Article  Google Scholar 

  26. 26

    Satoh, K., Matsuda, M., Nagai, K. & Kamigaito, M. AAB-sequence living radical chain copolymerization of naturally occurring limonene with maleimide: an end-to-end sequence-regulated copolymer. J. Am. Chem. Soc. 132, 10003–10005 (2010).

    CAS  Article  Google Scholar 

  27. 27

    Berthet, M. A., Zarafshani, Z., Pfeifer, S. & Lutz, J.-F. Facile synthesis of functional periodic copolymers: a step toward polymer-based molecular arrays. Macromolecules 43, 44–50 (2010).

    CAS  Article  Google Scholar 

  28. 28

    Ida, S., Terashima, T., Ouchi, M. & Sawamoto, M. Selective radical addition with a designed heterobifunctional halide: a primary study toward sequence-controlled polymerization upon template effect. J. Am. Chem. Soc. 131, 10808–10809 (2009).

    CAS  Article  Google Scholar 

  29. 29

    Pfeifer, S., Zarafshani, Z., Badi, N. & Lutz, J.-F. Liquid-phase synthesis of block copolymers containing sequence-ordered segments. J. Am. Chem. Soc. 131, 9195–9197 (2009).

    CAS  Article  Google Scholar 

  30. 30

    Kramer, J. W. et al. Polymerization of enantiopure monomers using syndiospecific catalysts: a new approach to sequence control in polymer synthesis. J. Am. Chem. Soc. 131, 16042–16044 (2009).

    CAS  Article  Google Scholar 

  31. 31

    Satoh, K., Ozawa, S., Mizutani, M., Nagai, K. & Kamigaito, M. Sequence-regulated vinyl copolymers by metal-catalysed step-growth radical polymerization. Nature Commun. 1, 6 (2010).

    Article  Google Scholar 

  32. 32

    Matyjaszewski, K. & Tsarevsky, N. V. Nanostructured functional materials prepared by atom transfer radical polymerization. Nature Chem. 1, 276–288 (2009).

    CAS  Article  Google Scholar 

  33. 33

    Ouchi, M., Terashima, T. & Sawamoto, M. Transition metal-catalyzed living radical polymerization: toward perfection in catalysis and precision polymer synthesis. Chem. Rev. 109, 4963–5050 (2009).

    CAS  Article  Google Scholar 

  34. 34

    Siemsen, P., Livingston, R. C. & Diederich, F. Acetylenic coupling: a powerful tool in molecular construction. Angew. Chem. Int. Ed. 39, 2633–2657 (2000).

    Article  Google Scholar 

  35. 35

    Himo, F. et al. Copper(I)-catalyzed synthesis of azoles. DFT study predicts unprecedented reactivity and intermediates. J. Am. Chem. Soc. 127, 210–216 (2004).

    Article  Google Scholar 

  36. 36

    Hawker, C. J. & Wooley, K. L. The convergence of synthetic organic and polymer chemistries. Science 309, 1200–1205 (2005).

    CAS  Article  Google Scholar 

  37. 37

    Lutz, J.-F. 1,3-Dipolar cycloadditions of azides and alkynes: a universal ligation tool in polymer and materials science. Angew. Chem. Int. Ed. 46, 1018–1025 (2007).

    CAS  Article  Google Scholar 

  38. 38

    Hanni, K. D. & Leigh, D. A. The application of CuAAC ‘click’ chemistry to catenane and rotaxane synthesis. Chem. Soc. Rev. 39, 1240–1251 (2010).

    Article  Google Scholar 

  39. 39

    Kricheldorf, H. R. Cyclic polymers: synthetic strategies and physical properties. J. Polym. Sci. A 48, 251–284 (2010).

    CAS  Article  Google Scholar 

  40. 40

    Roovers, J. & Toporowski, P. M. Synthesis of high molecular weight ring polystyrenes. Macromolecules 16, 843–849 (1983).

    CAS  Article  Google Scholar 

  41. 41

    Alberty, K. A., Hogen-Esch, T. E. & Carlotti, S. Synthesis and characterization of macrocyclic vinyl-aromatic polymers. Molecular weight-dependent glass transition temperatures and emission of macrocyclic polystyrene. Macromol. Chem. Phys. 206, 1035–1042 (2005).

    CAS  Article  Google Scholar 

  42. 42

    Benoit, D., Hawker, C. J., Huang, E. E., Lin, Z. & Russell, T. P. One-step formation of functionalized block copolymers. Macromolecules 33, 1505–1507 (2000).

    CAS  Article  Google Scholar 

  43. 43

    Antonietti, M. & Fölsch, K. J. Synthesis and characterization of ‘eight-shaped’ polystyrene. Makromol. Chem. Rapid Commun. 9, 423–430 (1988).

    CAS  Article  Google Scholar 

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The Fraunhofer Society is acknowledged for financial support. J.F.L. thanks the European Research Council for support (Project SEQUENCES). J.F.L. thanks A. Laschewsky (Universität Potsdam), C. Wieland (Universität Potsdam), P.J. Lutz (ICS Strasbourg) and M. Maaloum (Université de Strasbourg) for discussions.

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J.F.L designed the experiments, analysed the data and wrote the paper. B.V.K.J.S. and N.F. performed the experiments and analysed the data. J.F. contributed analysis tools. All authors discussed the results and commented on the manuscript.

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Correspondence to Jean-François Lutz.

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The authors declare no competing financial interests.

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Schmidt, B., Fechler, N., Falkenhagen, J. et al. Controlled folding of synthetic polymer chains through the formation of positionable covalent bridges. Nature Chem 3, 234–238 (2011).

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