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:

Sequence-controlled methacrylic multiblock copolymers via sulfur-free RAFT emulsion polymerization

Nature Chemistry volume 9, pages 171–178 (2017)Cite this article

Subjects

Abstract

Translating the precise monomer sequence control achieved in nature over macromolecular structure (for example, DNA) to whole synthetic systems has been limited due to the lack of efficient synthetic methodologies. So far, chemists have only been able to synthesize monomer sequence-controlled macromolecules by means of complex, time-consuming and iterative chemical strategies such as solid-state Merrifield-type approaches or molecularly dissolved solution-phase systems. Here, we report a rapid and quantitative synthesis of sequence-controlled multiblock polymers in discrete stable nanoscale compartments via an emulsion polymerization approach in which a vinyl-terminated macromolecule is used as an efficient chain-transfer agent. This approach is environmentally friendly, fully translatable to industry and thus represents a significant advance in the development of complex macromolecule synthesis, where a high level of molecular precision or monomer sequence control confers potential for molecular targeting, recognition and biocatalysis, as well as molecular information storage.

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

Figure 1: Structure of multiblock copolymers synthesized in this work by a combination of catalytic chain transfer polymerization (macromonomer synthesis) followed by sulfur-free RAFT emulsion polymerization.
Figure 2: Conceptual scheme for the synthesis of multiblock copolymers via sulfur-free RAFT emulsion polymerization.
Figure 3: Synthesis and characterization of model heneicasoblock BMA homopolymer via sulfur-free RAFT emulsion polymerization.
Figure 4: Scalable synthesis of the high-molecular-weight hexablock copolymer.
Figure 5: Synthesis and characterization of the undecablock copolymer following various patterns obtained via consecutively switching between different monomers.

Similar content being viewed by others

References

  1. 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 

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

    Article  PubMed  CAS  Google Scholar 

  3. 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 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  7. Vandenbergh, J., Reekmans, G., Adriaensens, P. & Junkers, T. Synthesis of sequence-defined acrylate oligomers via photo-induced copper-mediated radical monomer insertions. Chem. Sci. 6, 5753–5761 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Vandenbergh, J., Reekmans, G., Adriaensens, P. & Junkers, T. Synthesis of sequence controlled acrylate oligomers via consecutive RAFT monomer additions. Chem. Commun. 49, 10358–10360 (2013).

    Article  CAS  Google Scholar 

  9. 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 

  10. Ida, S., Ouchi, M. & Sawamoto, M. Template-assisted selective radical addition toward sequence-regulated polymerization: lariat capture of target monomer by template initiator. J. Am. Chem. Soc. 132, 14748–14750 (2010).

    Article  CAS  PubMed  Google Scholar 

  11. 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 

  12. Guo, Y., Zhang, J., Xie, P., Gao, X. & Luo, Y. Tailor-made compositional gradient copolymer by a many-shot RAFT emulsion polymerization method. Polym. Chem. 5, 3363–3371 (2014).

    Article  CAS  Google Scholar 

  13. 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 

  14. Hartmann, L. & Börner, H. G. Precision polymers: monodisperse, monomer-sequence-defined segments to target future demands of polymers in medicine. Adv. Mater. 21, 3425–3431 (2009).

    Article  CAS  PubMed  Google Scholar 

  15. Zuckermann, R. N., Kerr, J. M., Kent, S. B. H. & Moos, W. H. Efficient method for the preparation of peptoids [oligo (N-substituted glycines)] by submonomer solid-phase synthesis. J. Am. Chem. Soc. 114, 10646–10647 (1992).

    Article  CAS  Google Scholar 

  16. 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 

  17. Ueda, M. Sequence control in one-step condensation polymerization. Prog. Polym. Sci. 24, 699–730 (1999).

    Article  CAS  Google Scholar 

  18. Bayer, E. & Mutter, M. Liquid phase synthesis of peptides. Nature 237, 512–513 (1972).

    Article  CAS  PubMed  Google Scholar 

  19. Barnes, J. C. et al. Iterative exponential growth of stereo- and sequence-controlled polymers. Nat. Chem. 7, 810–815 (2015).

    Article  CAS  PubMed  Google Scholar 

  20. 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 

  21. Anastasaki, A. et al. High molecular weight block copolymers by sequential monomer addition via Cu(0)-mediated living radical polymerization (SET-LRP): an optimized approach. ACS Macro Lett. 2, 896–900 (2013).

    Article  CAS  Google Scholar 

  22. 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 

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

    Article  CAS  Google Scholar 

  24. Alsubaie, F., Anastasaki, A., Wilson, P. & Haddleton, D. M. Sequence-controlled multi-block copolymerization of acrylamides via aqueous SET-LRP at 0 °C. Polym. Chem. 6, 406–417 (2015).

    Article  CAS  Google Scholar 

  25. 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 

  26. Vandenbergh, J. & Junkers, T. Alpha and omega: importance of the nonliving chain End in RAFT multiblock copolymerization. Macromolecules 47, 5051–5059 (2014).

    Article  CAS  Google Scholar 

  27. 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  Google Scholar 

  28. 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 

  29. Martin, L., Gody, G. & Perrier, S. Preparation of complex multiblock copolymers via aqueous RAFT polymerization at room temperature. Polym. Chem. 6, 4875–4886 (2015).

    Article  CAS  Google Scholar 

  30. Junkers, T. & Wenn, B. Continuous photoflow synthesis of precision polymers. React. Chem. Eng. 1, 60–64 (2016).

    Article  CAS  Google Scholar 

  31. Wenn, B., Martens, A. C., 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 

  32. 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 

  33. Zetterlund, P. B., Thickett, S. C., Perrier, S., Bourgeat-Lami, E. & Lansalot, M. Controlled/living radical polymerization in dispersed systems: an update. Chem. Rev. 115, 9745–9800 (2015).

    Article  CAS  PubMed  Google Scholar 

  34. Truong, N. P. et al. Facile production of nanoaggregates with tuneable morphologies from thermoresponsive P(DEGMA-co-HPMA). Polym. Chem. 7, 430–440 (2016).

    Article  CAS  Google Scholar 

  35. Moad, C. L., Moad, G., Rizzardo, E. & Thang, S. H. Chain transfer activity of ω-unsaturated methyl methacrylate oligomers. Macromolecules 29, 7717–7726 (1996).

    Article  CAS  Google Scholar 

  36. Hutson, L. et al. Chain transfer activity of ω-unsaturated methacrylic oligomers in polymerizations of methacrylic monomers. Macromolecules 37, 4441–4452 (2004).

    Article  CAS  Google Scholar 

  37. Suddaby, K. G., Haddleton, D. M., Hastings, J. J., Richards, S. N. & O'Donnell, J. P. Catalytic chain transfer for molecular weight control in the emulsion polymerization of methyl methacrylate and methyl methacrylate−styrene. Macromolecules 29, 8083–8091 (1996).

    Article  CAS  Google Scholar 

  38. Kukulj, D., Davis, T. P., Suddaby, K. G., Haddleton, D. M. & Gilbert, R. G. Catalytic chain transfer for molecular weight control in the emulsion homo- and copolymerizations of methyl methacrylate and butyl methacrylate. J. Polym. Sci. A 35, 859–878 (1997).

    Article  CAS  Google Scholar 

  39. Haddleton, D. M., Maloney, D. R., Suddaby Adam Clarke, K. G. & Richards, S. N. Radical-addition-fragmentation and co-polymerization of methyl methacrylate macromonomers from catalytic chain transfer polymerization (CCTP). Polymer 38, 6207–6217 (1997).

    Article  CAS  Google Scholar 

  40. Haddleton, D. M., Maloney, D. R. & Suddaby, K. G. Competition between β-scission of macromonomer-ended radicals and chain transfer to cobalt(II) in catalytic chain transfer polymerization (CCTP). Macromolecules 29, 481–483 (1996).

    Article  CAS  Google Scholar 

  41. Krstina, J. et al. Narrow polydispersity block copolymers by free-radical polymerization in the presence of macromonomers. Macromolecules 28, 5381–5385 (1995).

    Article  CAS  Google Scholar 

  42. 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  PubMed  PubMed Central  CAS  Google Scholar 

  43. Heuts, J. P. A. & Smeets, N. M. B. Catalytic chain transfer and its derived macromonomers. Polym. Chem. 2, 2407–2423 (2011).

    Article  CAS  Google Scholar 

  44. Buback, M., Kurz, C. H. & Schmaltz, C. Pressure dependence of propagation rate coefficients in free-radical homopolymerizations of methyl acrylate and dodecyl acrylate. Macromol. Chem. Phys. 199, 1721–1727 (1998).

    Article  CAS  Google Scholar 

  45. Beuermann, S. et al. Critically evaluated rate coefficients for free-radical polymerization, 2. Propagation rate coefficients for methyl methacrylate. Macromol. Chem. Phys. 198, 1545–1560 (1997).

    Article  CAS  Google Scholar 

  46. Zammit, M. D., Coote, M. L., Davis, T. P. & Willett, G. D. Effect of the ester side-chain on the propagation kinetics of alkyl methacrylates. An entropic or enthalpic effect? Macromolecules 31, 955–963 (1998).

    Article  CAS  Google Scholar 

  47. Truong, N. P., Dussert, M. V., Whittaker, M. R., Quinn, J. F. & Davis, T. P. Rapid synthesis of ultrahigh molecular weight and low polydispersity polystyrene diblock copolymers by RAFT-mediated emulsion polymerization. Polym. Chem. 6, 3865–3874 (2015).

    Article  CAS  Google Scholar 

  48. Gilbert, R. G. Emulsion Polymerization: A Mechanistic Approach (Academic, 1995).

    Google Scholar 

  49. Chang, C.-W., Bays, E., Tao, L., Alconcel, S. N. S. & Maynard, H. D. Differences in cytotoxicity of poly (PEGA)s synthesized by reversible addition–fragmentation chain transfer polymerization. Chem. Commun. 3580–3582 (2009).

  50. Pissuwan, D., Boyer, C., Gunasekaran, K., Davis, T. P. & Bulmus, V. In vitro cytotoxicity of RAFT polymers. Biomacromolecules 11, 412–420 (2010).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors acknowledge financial support from the University of Warwick, the Australian Research Council (ARC) Centre of Excellence in Convergent Bio-Nano Science and Technology (CE140100036) and Lubrizol (to N.G.E.). D.M.H. is a Wolfson/Royal Society Research Fellow. The authors acknowledge the facilities and personnel (A.A., M.R.W., T.P.D. and D.M.H.) enabled by the Monash–Warwick Alliance.

Author information

Author notes

  1. Nikolaos G. Engelis and Athina Anastasaki: These authors contributed equally to this work

Authors and Affiliations

  1. Chemistry Department, University of Warwick, Library Road, Coventry, CV4 7AL, UK

    Nikolaos G. Engelis, Athina Anastasaki, Gabit Nurumbetov, Vasiliki Nikolaou, Ataulla Shegiwal, Thomas P. Davis & David M. Haddleton

  2. ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 399 Royal Parade, Parkville, 3152, Victoria, Australia

    Athina Anastasaki, Nghia P. Truong, Michael R. Whittaker, Thomas P. Davis & David M. Haddleton

Authors
  1. Nikolaos G. Engelis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Athina Anastasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gabit Nurumbetov
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nghia P. Truong
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Vasiliki Nikolaou
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ataulla Shegiwal
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Michael R. Whittaker
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Thomas P. Davis
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. David M. Haddleton
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

A.A., D.M.H. and T.P.D. conceived and designed the experiments. N.G.E. and A.A. performed the experiments. N.G.E., A.A., and V.N. analysed the data with input from G.N, N.P.T., A.S. and M.R.W. A.A. and N.G.E. co-wrote the paper. All authors discussed the results and commented on the manuscript. A.A. and N.G.E. contributed equally to this work.

Corresponding authors

Correspondence to Athina Anastasaki, Thomas P. Davis or David M. Haddleton.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary information

Supplementary information (PDF 2168 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Engelis, N., Anastasaki, A., Nurumbetov, G. et al. Sequence-controlled methacrylic multiblock copolymers via sulfur-free RAFT emulsion polymerization. Nature Chem 9, 171–178 (2017). https://doi.org/10.1038/nchem.2634

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchem.2634

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