Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Concurrent control over sequence and dispersity in multiblock copolymers

Nature Chemistry volume 14, pages 304–312 (2022)Cite this article

Subjects

Abstract

Controlling monomer sequence and dispersity in synthetic macromolecules is a major goal in polymer science as both parameters determine materials’ properties and functions. However, synthetic approaches that can simultaneously control both sequence and dispersity remain experimentally unattainable. Here we report a simple, one pot and rapid synthesis of sequence-controlled multiblocks with on-demand control over dispersity while maintaining a high livingness, and good agreement between theoretical and experimental molecular weights and quantitative yields. Key to our approach is the regulation in the activity of the chain transfer agent during a controlled radical polymerization that enables the preparation of multiblocks with gradually ascending (Ɖ = 1.16 → 1.60), descending (Ɖ = 1.66 → 1.22), alternating low and high dispersity values (Ɖ = 1.17 → 1.61 → 1.24 → 1.70 → 1.26) or any combination thereof. We further demonstrate the potential of our methodology through the synthesis of highly ordered pentablock, octablock and decablock copolymers, which yield multiblocks with concurrent control over both sequence and dispersity.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Schematic representation of our proposed approach to the preparation of multiblocks with a tunable dispersity.
Fig. 2: Pentablock copolymers with gradually evolving dispersity.
Fig. 3: Diblock copolymers synthesized with dispersity value extremes by switching the activity of the RAFT agent.
Fig. 4: Pentablock copolymers synthesized with dispersity extremes.
Fig. 5: Decablock copolymers synthesized with tunable dispersity.

Similar content being viewed by others

Data availability

Data and are available within this article and its Supplementary Information. Source data are provided with this paper.

References

  1. Lutz, J.-F., Ouchi, M., Liu, D. R. & Sawamoto, M. Sequence-controlled polymers. Science 341, 1238149 (2013).

    Article  PubMed  CAS  Google Scholar 

  2. Ouchi, M., Badi, N., Lutz, J.-F. & Sawamoto, M. Single-chain technology using discrete synthetic macromolecules. Nat. Chem. 3, 917–924 (2011).

    Article  CAS  PubMed  Google Scholar 

  3. Lutz, J. F. Defining the field of sequence‐controlled polymers. Macromol. Rapid Commun. 38, 1700582 (2017).

    Article  CAS  Google Scholar 

  4. De Neve, J., Haven, J. J., Maes, L. & Junkers, T. Sequence-definition from controlled polymerization: the next generation of materials. Polym. Chem. 9, 4692–4705 (2018).

    Article  Google Scholar 

  5. Haven, J. J. et al. Elements of RAFT navigation: RAFT 20 years later: RAFT-synthesis of uniform, sequence-defined (co)polymers. ACS Symp. Ser. 1284, 77–103 (2018).

    Article  CAS  Google Scholar 

  6. Bates, F. S. et al. Multiblock polymers: panacea or Pandora’s box? Science 336, 434–440 (2012).

    Article  CAS  PubMed  Google Scholar 

  7. Parkatzidis, K., Wang, H. S., Truong, N. P. & Anastasaki, A. Recent developments and future challenges in controlled radical polymerization: a 2020 update. Chem 6, 1575–1588 (2020).

    Article  CAS  Google Scholar 

  8. Merrifield, R. B. Solid phase peptide synthesis. I. The synthesis of a tetrapeptide. J. Am. Chem. Soc. 85, 2149–2154 (1963).

    Article  CAS  Google Scholar 

  9. Zamfir, M. & Lutz, J.-F. Ultra-precise insertion of functional monomers in chain-growth polymerizations. Nat. Commun. 3, 1138 (2012).

    Article  CAS  Google Scholar 

  10. McHale, R., Patterson, J. P., Zetterlund, P. B. & O’Reilly, R. K. Biomimetic radical polymerization via cooperative assembly of segregating templates. Nat. Chem. 4, 491–497 (2012).

    Article  CAS  PubMed  Google Scholar 

  11. Schoonen, L. & van Hest, J. C. Compartmentalization approaches in soft matter science: from nanoreactor development to organelle mimics. Adv. Mater. 28, 1109–1128 (2016).

    Article  CAS  PubMed  Google Scholar 

  12. 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).

    Article  CAS  PubMed  Google Scholar 

  13. Nakatani, K., Ogura, Y., Koda, Y., Terashima, T. & Sawamoto, M. Sequence-regulated copolymers via tandem catalysis of living radical polymerization and in situ transesterification. J. Am. Chem. Soc. 134, 4373–4383 (2012).

    Article  CAS  PubMed  Google Scholar 

  14. 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).

    Article  CAS  PubMed  Google Scholar 

  15. Dong, R. et al. Sequence-defined multifunctional polyethers via liquid-phase synthesis with molecular sieving. Nat. Chem. 11, 136–145 (2019).

    Article  CAS  PubMed  Google Scholar 

  16. Beyer, V. P., Kim, J. & Becer, C. R. Synthetic approaches for multiblock copolymers. Polym. Chem. 11, 1271–1291 (2020).

    Article  CAS  Google Scholar 

  17. Elacqua, E. et al. Supramolecular multiblock copolymers featuring complex secondary structures. J. Am. Chem. Soc. 139, 12240–12250 (2017).

    Article  CAS  PubMed  Google Scholar 

  18. Heiler, C., Offenloch, J. T., Blasco, E. & Barner-Kowollik, C. Photochemically induced folding of single chain polymer nanoparticles in water. ACS Macro Lett. 6, 56–61 (2017).

    Article  CAS  PubMed  Google Scholar 

  19. Zhang, J. et al. Synthesis of sequence-controlled multiblock single chain nanoparticles by a stepwise folding–chain extension–folding process. Macromolecules 49, 8933–8942 (2016).

    Article  CAS  Google Scholar 

  20. Guimarães, T. R. et al. Nano-engineered multiblock copolymer nanoparticles via reversible addition–fragmentation chain transfer emulsion polymerization. Macromolecules 52, 2965–2974 (2019).

    Article  CAS  Google Scholar 

  21. Anastasaki, A. et al. One‐pot synthesis of ABCDE multiblock copolymers with hydrophobic, hydrophilic, and semi‐fluorinated segments. Angew. Chem. Int. Ed. 56, 14483–14487 (2017).

    Article  CAS  Google Scholar 

  22. Barbon, S. M. et al. Elucidating the effect of sequence and degree of polymerization on antimicrobial properties for block copolymers. Polym. Chem. 11, 84–90 (2020).

    Article  CAS  Google Scholar 

  23. Kuroki, A. et al. Sequence control as a powerful tool for improving the selectivity of antimicrobial polymers. ACS Appl. Mater. Inter. 9, 40117–40126 (2017).

    Article  CAS  Google Scholar 

  24. Judzewitsch, P. R., Nguyen, T. K., Shanmugam, S., Wong, E. H. & Boyer, C. Towards sequence‐controlled antimicrobial polymers: effect of polymer block order on antimicrobial activity. Angew. Chem. 130, 4649–4654 (2018).

    Article  Google Scholar 

  25. Zhang, J. et al. Effect of hydrophilic monomer distribution on self‐assembly of a pH‐responsive copolymer: spheres, worms and vesicles from a single copolymer composition. Angew. Chem. Int. Ed. 59, 2–8 (2020).

    Article  CAS  Google Scholar 

  26. Chin, S. M., He, H., Konkolewicz, D. & Matyjaszewski, K. Synthesis of triblock and multiblock methacrylate polymers and self‐assembly of stimuli responsive triblock polymers. J. Polym. Sci. Pol. Chem. 52, 2548–2555 (2014).

    Article  CAS  Google Scholar 

  27. Shanmugam, S. & Boyer, C. Stereo-, temporal and chemical control through photoactivation of living radical polymerization: synthesis of block and gradient copolymers. J. Am. Chem. Soc. 137, 9988–9999 (2015).

    Article  CAS  PubMed  Google Scholar 

  28. Xu, J., Jung, K., Atme, A., Shanmugam, S. & Boyer, C. A robust and versatile photoinduced living polymerization of conjugated and unconjugated monomers and its oxygen tolerance. J. Am. Chem. Soc. 136, 5508–5519 (2014).

    Article  CAS  PubMed  Google Scholar 

  29. Soeriyadi, A. H., Boyer, C., Nyström, F., Zetterlund, P. B. & Whittaker, M. R. High-order multiblock copolymers via iterative Cu(0)-mediated radical polymerizations (SET-LRP): toward biological precision. J. Am. Chem. Soc. 133, 11128–11131 (2011).

    Article  CAS  PubMed  Google Scholar 

  30. Boyer, C., Derveaux, A., Zetterlund, P. B. & Whittaker, M. R. Synthesis of multi-block copolymer stars using a simple iterative Cu(0)-mediated radical polymerization technique. Polym. Chem. 3, 117–123 (2012).

    Article  CAS  Google Scholar 

  31. Boyer, C., Soeriyadi, A. H., Zetterlund, P. B. & Whittaker, M. R. Synthesis of complex multiblock copolymers via a simple iterative Cu(0)-mediated radical polymerization approach. Macromolecules 44, 8028–8033 (2011).

    Article  CAS  Google Scholar 

  32. Engelis, N. G. et al. Sequence-controlled methacrylic multiblock copolymers via sulfur-free RAFT emulsion polymerization. Nat. Chem. 9, 171–178 (2017).

    Article  CAS  PubMed  Google Scholar 

  33. Anastasaki, A. et al. Photoinduced sequence-control via one pot living radical polymerization of acrylates. Chem. Sci. 5, 3536–3542 (2014).

    Article  CAS  Google Scholar 

  34. Zhang, Q. et al. Sequence‐controlled multi‐block glycopolymers to inhibit DC‐SIGN‐gp120 binding. Angew. Chem. Int. Ed. 52, 4435–4439 (2013).

    Article  CAS  Google Scholar 

  35. Chuang, Y.-M., Ethirajan, A. & Junkers, T. Photoinduced sequence-controlled copper-mediated polymerization: synthesis of decablock copolymers. ACS Macro Lett. 3, 732–737 (2014).

    Article  CAS  PubMed  Google Scholar 

  36. Wenn, B., Martens, A., Chuang, Y.-M., Gruber, J. & Junkers, T. Efficient multiblock star polymer synthesis from photo-induced copper-mediated polymerization with up to 21 arms. Polym. Chem. 7, 2720–2727 (2016).

    Article  CAS  Google Scholar 

  37. Debuigne, A., Detrembleur, C., Jérôme, C. & Junkers, T. Straightforward synthesis of symmetrical multiblock copolymers by simultaneous block extension and radical coupling reactions. Macromolecules 46, 8922–8931 (2013).

    Article  CAS  Google Scholar 

  38. Gody, G., Maschmeyer, T., Zetterlund, P. B. & Perrier, S. Rapid and quantitative one-pot synthesis of sequence-controlled polymers by radical polymerization. Nat. Commun. 4, 2505 (2013).

    Article  PubMed  CAS  Google Scholar 

  39. Gody, G., Barbey, R., Danial, M. & Perrier, S. Ultrafast RAFT polymerization: multiblock copolymers within minutes. Polym. Chem. 6, 1502–1511 (2015).

    Article  CAS  Google Scholar 

  40. Clothier, G. K. et al. Exploitation of the nanoreactor concept for efficient synthesis of multiblock copolymers via macroRAFT-mediated emulsion polymerization. ACS Macro Lett. 8, 989–995 (2019).

    Article  CAS  PubMed  Google Scholar 

  41. Gody, G., Maschmeyer, T., Zetterlund, P. B. & Perrier, S. B. Pushing the limit of the RAFT process: multiblock copolymers by one-pot rapid multiple chain extensions at full monomer conversion. Macromolecules 47, 3451–3460 (2014).

    Article  CAS  Google Scholar 

  42. Anastasaki, A. et al. Photoinduced synthesis of α,ω-telechelic sequence-controlled multiblock copolymers. Macromolecules 48, 1404–1411 (2015).

    Article  CAS  Google Scholar 

  43. Gentekos, D. T., Sifri, R. J. & Fors, B. P. Controlling polymer properties through the shape of the molecular-weight distribution. Nat. Rev. Mater. 4, 761–774 (2019).

    Article  Google Scholar 

  44. Whitfield, R. et al. Tailoring polymer dispersity and shape of molecular weight distributions: methods and applications. Chem. Sci. 10, 8724–8734 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Junkers, T. Polymers in the blender. Macromol. Chem. Phys. 221, 2000234 (2020).

    Article  CAS  Google Scholar 

  46. Liu, D., Sponza, A. D., Yang, D. & Chiu, M. Modulating polymer dispersity with light: cationic polymerization of vinyl ethers using photochromic initiators. Angew. Chem. Int. Ed. 58, 16210–16216 (2019).

    Article  CAS  Google Scholar 

  47. Liu, X., Wang, C. G. & Goto, A. Polymer dispersity control by organocatalyzed living radical polymerization. Angew. Chem. 131, 5654–5659 (2019).

    Article  Google Scholar 

  48. Gentekos, D. T., Dupuis, L. N. & Fors, B. P. Beyond dispersity: deterministic control of polymer molecular weight distribution. J. Am. Chem. Soc. 138, 1848–1851 (2016).

    Article  CAS  PubMed  Google Scholar 

  49. Gentekos, D. T. et al. Exploiting molecular weight distribution shape to tune domain spacing in block copolymer thin films. J. Am. Chem. Soc. 140, 4639–4648 (2018).

    Article  CAS  PubMed  Google Scholar 

  50. Kottisch, V., Gentekos, D. T. & Fors, B. P. ‘Shaping’ the future of molecular weight distributions in anionic polymerization. ACS Macro Lett. 5, 796–800 (2016).

    Article  CAS  PubMed  Google Scholar 

  51. Nadgorny, M. et al. Manipulation of molecular weight distribution shape as a new strategy to control processing parameters. Macromol. Rapid Commun. 38, 1700352 (2017).

    Article  CAS  Google Scholar 

  52. Wang, Z. et al. Control of dispersity and grafting density of particle brushes by variation of ATRP catalyst concentration. ACS Macro Lett. 8, 859–864 (2019).

    Article  CAS  PubMed  Google Scholar 

  53. Plichta, A., Zhong, M., Li, W., Elsen, A. M. & Matyjaszewski, K. Tuning dispersity in diblock copolymers using ARGET ATRP. Macromol. Chem. Phys. 213, 2659–2668 (2012).

    Article  CAS  Google Scholar 

  54. Whitfield, R., Parkatzidis, K., Truong, N. P., Junkers, T. & Anastasaki, A. Tailoring polymer dispersity by raft polymerization: a versatile approach. Chem 6, 1340–1352 (2020).

    Article  CAS  Google Scholar 

  55. Parkatzidis, K. et al. Tailoring polymer dispersity by mixing chain transfer agents in PET-RAFT polymerization. Polym. Chem. 11, 4968–4972 (2020).

    Article  CAS  Google Scholar 

  56. Rolland, M., Truong, N. P., Whitfield, R. & Anastasaki, A. Tailoring polymer dispersity in photoinduced iron-catalyzed ATRP. ACS Macro Lett. 9, 459–463 (2020).

    Article  CAS  PubMed  Google Scholar 

  57. Whitfield, R., Parkatzidis, K., Rolland, M., Truong, N. P. & Anastasaki, A. Tuning dispersity by photoinduced atom transfer radical polymerisation: monomodal distributions with ppm copper concentration. Angew. Chem. Int. Ed. 58, 13323–13328 (2019).

    Article  CAS  Google Scholar 

  58. Benaglia, M. et al. Polystyrene-block-poly (vinyl acetate) through the use of a switchable RAFT agent. Macromolecules 42, 9384–9386 (2009).

    Article  CAS  Google Scholar 

  59. Benaglia, M. et al. Universal (switchable) RAFT agents. J. Am. Chem. Soc. 131, 6914–6915 (2009).

    Article  CAS  PubMed  Google Scholar 

  60. Moad, G., Keddie, D., Guerrero‐Sanchez, C., Rizzardo, E. & Tang, S.H. Advances in switchable RAFT polymerization. Macromol. Symp. 350, 34–42 (2015).

    Article  CAS  Google Scholar 

  61. Keddie, D. J., Guerrero-Sanchez, C., Moad, G., Rizzardo, E. & Thang, S. H. Switchable reversible addition–fragmentation chain transfer (RAFT) polymerization in aqueous solution, N,N-dimethylacrylamide. Macromolecules 44, 6738–6745 (2011).

    Article  CAS  Google Scholar 

  62. Fraenkel, G. & Franconi, C. Protonation of amides 1. J. Am. Chem. Soc. 82, 4478–4483 (1960).

    Article  CAS  Google Scholar 

  63. Farona, M., Ayers, W., Ramsey, B. & Graselli, J. Acrylamide and N,N-dimethylacrylamide complexes. II. N-protonation and N-bonding to some transition metal perchlorates and tetrafluouroborates. Inorg. Chim. Acta 3, 503–507 (1969).

    Article  CAS  Google Scholar 

  64. Yadav, V. et al. Dispersity control in atom transfer radical polymerizations through addition of phenylhydrazine. Polym. Chem. 9, 4332–4342 (2018).

    Article  CAS  Google Scholar 

  65. Harrisson, S. The chain length distribution of an ideal reversible deactivation radical polymerization. Polymers 10, 887 (2018).

    Article  PubMed Central  CAS  Google Scholar 

  66. Gody, G., Zetterlund, P. B., Perrier, S. & Harrisson, S. The limits of precision monomer placement in chain growth polymerization. Nat. Commun. 7, 10514 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Kurov, G., Afonin, A., Svyatkina, L., Dmitrieva, L. & Pal’chuk, E. Structure and hydrolytic activity of N-vinyl derivatives of phenothiazine, carbazole and acridone. Russ. Chem. B 36, 403–405 (1987).

    Article  Google Scholar 

  68. Harrisson, S. et al. RAFT polymerization of vinyl esters: synthesis and applications. Polymers 6, 1437–1488 (2014).

    Article  CAS  Google Scholar 

  69. Perrier, S. B. 50th anniversary perspective: RAFT polymerization—a user guide. Macromolecules 50, 7433–7447 (2017).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

A.A. acknowledges ETH Zurich (Switzerland) for financial support. N.P.T. acknowledges the award of a DECRA Fellowship from the ARC (DE180100076). We acknowledge M. Rolland for her artistic contribution in the conceptual figure. Finally, we acknowledge L. Bigler and U. Stadler (University of Zurich) for access to matrix-assisted desorption ionization time-of-flight mass spectrometry.

Author information

Authors and Affiliations

  1. Laboratory of Polymeric Materials, Department of Materials, ETH Zürich, Zürich, Switzerland

    Maria-Nefeli Antonopoulou, Richard Whitfield, Nghia P. Truong & Athina Anastasaki

  2. Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia

    Nghia P. Truong

  3. Polymer Reaction Design Group, School of Chemistry, Monash University, Clayton, Victoria, Australia

    Dries Wyers & Tanja Junkers

  4. Laboratoire de Chimie des Polymères Organiques, University of Bordeaux/ENSCBP/CNRS UMR5629, Pessac, France

    Simon Harrisson

Authors
  1. Maria-Nefeli Antonopoulou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Richard Whitfield
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nghia P. Truong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dries Wyers
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Simon Harrisson
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tanja Junkers
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Athina Anastasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

A.A. conceived the initial idea and managed the overall project; M.-N.A., N.P.T. and A.A. designed the experiments; M.-N.A performed the vast majority of the experiments and analysed the data with input from A.A., N.P.T. and R.W.; M.-N.A. and A.A. co-wrote the manuscript with input from N.P.T. and R.W. During the revisions, S.H., T.J. and D.W. were added as co-authors. D.W. and T.J. performed the electrospray ionization–mass spectrometry measurements and the Predici simulations and S.H. conducted the calculations for the percentage of defective chains. All the authors discussed the results and commented on the manuscript.

Corresponding author

Correspondence to Athina Anastasaki.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Peer review information Nature Chemistry thanks Graeme Moad, Shigeru Yamago and the other, anonymous, reviewer(s) 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.

Supplementary information

Supplementary Information

Supplementary Figs. 1–40, Schemes 1–3, Tables 1–28. Supplementary discussion and experimental procedures.

Source data

Source Data Fig. 2

NMR and GPC source data.

Source Data Fig. 3

NMR and GPC source data.

Source Data Fig. 4

NMR and GPC source data.

Source Data Fig. 5

NMR and GPC source data.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Antonopoulou, MN., Whitfield, R., Truong, N.P. et al. Concurrent control over sequence and dispersity in multiblock copolymers. Nat. Chem. 14, 304–312 (2022). https://doi.org/10.1038/s41557-021-00818-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41557-021-00818-8

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing