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.

  • Original Article
  • Published:

Microphase separation of double-hydrophilic poly(carboxybetaine acrylate)-poly(2-methoxyethyl acrylate) block copolymers in water

Polymer Journal volume 55, pages 1357–1365 (2023)Cite this article

Subjects

Abstract

The microphase separation of double-hydrophilic block copolymers in water is of interest when these copolymers are utilized as molecular assemblies with mesoscale aqueous compartments. Diblock copolymers composed of a water-soluble zwitterionic polymer, poly(carboxybetaine acrylate) (PCBA2), and a hydrophilic water-insoluble nonionic polymer, poly(2-methoxyethyl acrylate) (PMEA), (PCBA2n-b-PMEAm) were synthesized, and their assembly characteristics were investigated in aqueous solutions. Well-defined PCBA2n-b-PMEAm block copolymers were synthesized by the reversible addition–fragmentation chain transfer polymerization of a carboxybetaine acrylate modified with a tert-butyl group and 2-methoxyethyl acrylate followed by tert-butyl group cleavage. PCBA2n-b-PMEAm produced particles in dilute aqueous solutions and microphase-separated structures in concentrated aqueous solutions. The hydrodynamic radius of the particles and the microphase-separated structure were associated with the block copolymer composition and degree of polymerization of the PMEA chain. The molecular assembly behavior was tolerant to NaCl concentration, providing molecular design guidelines for the use of double-hydrophilic microphase-separated compartments in physiological environments.

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

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Keating CD. Aqueous phase separation as a possible route to compartmentalization of biological molecules. Acc Chem Res. 2012;45:2114–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Long MS, Jones CD, Helfrich MR, Mangeney-Slavin LK, Keating CD. Dynamic microcompartmentation in synthetic cells. PNAS. 2005;102:5920–5.

    Article  CAS  PubMed Central  Google Scholar 

  3. Mace CR, Akbulut O, Kumar AA, Shapiro ND, Derda R, Patton MR, et al. Aqueous multiphase systems of polymers and surfactants provide self-assembling step-gradients in density. J Am Chem Soc. 2012;134:9094–7.

    Article  CAS  PubMed  Google Scholar 

  4. Hamley IW. Block copolymers in solution: Fundamentals and applications. Chichester, England: John Wiley & Sons, Ltd.; 2005.

    Book  Google Scholar 

  5. Zhao H, Ibrahimova V, Garanger E, Lecommandoux S. Dynamic spatial formation and distribution of intrinsically disordered protein droplets in macromolecularly crowded protocells. Angew Chem. 2020;132:11121–9.

    Article  Google Scholar 

  6. Sakuta H, Fujita F, Hamada T, Hayashi M, Takiguchi K, Tsumoto K, et al. Self-emergent protocells generated in an aqueous solution with binary macromolecules through liquid-liquid phase separation. ChemBioChem. 2020;21:3323–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Shono M, Ito R, Fujita F, Sakuta H, Yoshikawa K. Emergence of uniform linearly‑arranged micro‑droplets entrapping DNA and living cells through water/water phase‑separation. Sci Rep. 2021;11:23570.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Schmidt BVKJ. Double hydrophilic block copolymer self-assembly in aqueous solution. Macromol Chem Phys. 2018;219:1700494.

    Article  Google Scholar 

  9. Casse O, Shkilnyy A, Linders Jr, Mayer C, Häussinger D, Völkel A, et al. Solution behavior of double-hydrophilic block copolymers in dilute aqueous solution. Macromolecules 2012;45:4772–7.

  10. Taubert A, Furrer E, Meier W Water-in-water mesophases for templating inorganics. Chem Commun. 2004;2170–1. https://pubs.rsc.org/en/content/articlelanding/2004/cc/b405610h/unauth.

  11. Blanazs A, Warren NJ, Lewis AL, Armes SP, Ryan AJ. Self-assembly of double hydrophilic block copolymers in concentrated aqueous solution. Soft Matter. 2011;7:6399.

    Article  CAS  Google Scholar 

  12. Willersinn J, Schmidt BVKJ. Self-assembly of double hydrophilic poly(2-ethyl-2-oxazoline)-b-poly(n-vinylpyrrolidone) block copolymers in aqueous solution. Polymers. 2017;9:293.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Oh T, Nagao M, Hoshino Y, Miura Y. Self-assembly of a double hydrophilic block glycopolymer and the investigation of its mechanism. Langmuir. 2018;34:8591–8.

    Article  CAS  PubMed  Google Scholar 

  14. Brosnan SM, Schlaad H, Antonietti M. Aqueous self-assembly of purely hydrophilic block copolymers into giant vesicles. Angew Chem Int Ed. 2015;54:9715–8.

    Article  CAS  Google Scholar 

  15. Lira RB, Willersinn J, Schmidt BVKJ, Dimova R. Selective partitioning of (biomacro)molecules in the crowded environment of double-hydrophilic block copolymers. Macromolecules. 2020;53:10179–88.

    Article  CAS  Google Scholar 

  16. Rodríguez-Hernández J, Lecommandoux S. Reversible inside-out micellization of pH-responsive and water-soluble vesicles based on polypeptide diblock copolymers. J Am Chem Soc. 2005;127:2026–7.

    Article  PubMed  Google Scholar 

  17. Takahashi M, Shimizu A, Yusa S-I, Higaki Y. Lyotropic morphology transition of double zwitterionic diblock copolymer aqueous solutions. Macromol Chem Phys. 2021;222:2000377.

    Article  CAS  Google Scholar 

  18. Shimizu A, Hifumi E, Kojio K, Takahara A, Higaki Y. Modulation of double zwitterionic block copolymer aggregates by zwitterion-specific interactions. Langmuir. 2021;37:14760–6.

    Article  CAS  PubMed  Google Scholar 

  19. Higaki Y, Takahashi M, Masuda T. Phase behavior of double zwitterionic block copolymers in water: Morphology transition through concentration dependent selectivity of water partitioning. Macromol Chem Phys. 2023;224:2200416.

    Article  CAS  Google Scholar 

  20. Tanaka M, Hayashi T, Morita S. The roles of water molecules at the biointerface of medical polymers. Polym J. 2013;45:701–10.

    Article  CAS  Google Scholar 

  21. Murakami D, Yamazoe K, Nishimura S-N, Kurahashi N, Ueda T, Miyawaki J, et al. Hydration mechanism in blood-compatible polymers undergoing phase separation. Langmuir. 2022;38:1090–8.

    Article  CAS  PubMed  Google Scholar 

  22. Tanaka M, Mochizuki A, Ishii N, Motomura T, Hatakeyama T. Study of blood compatibility with poly(2-methoxyethyl acrylate). Relationship between water structure and platelet compatibility in poly(2-methoxyethylacrylate-co-2-hydroxyethylmethacrylate). Biomacromolecules. 2002;3:36–41.

    Article  CAS  PubMed  Google Scholar 

  23. Li G, Ye S, Morita S, Nishida T, Osawa M. Hydrogen bonding on the surface of poly (2-methoxyethyl acrylate). J Am Chem Soc. 2004;126:12198–9.

    Article  CAS  PubMed  Google Scholar 

  24. Vancoillie G, Frank D, Hoogenboom R. Thermoresponsive poly(oligo ethylene glycol acrylates). Prog Polym Sci. 2014;39:1074–95.

    Article  CAS  Google Scholar 

  25. Tsuji A, Nguyen TL, Mizoue Y, Ishihara K, Yusa S-I. Water-soluble polymer micelles formed from amphiphilic diblock copolymers bearing pendant phosphorylcholine and methoxyethyl groups. Polym J. 2021;53:805–14.

    Article  CAS  Google Scholar 

  26. Nguyen TL, Kawata Y, Ishihara K, Yusa S-I Synthesis of amphiphilic statistical copolymers bearing methoxyethyl and phosphorylcholine groups and their self-association behavior in water. Polymers. 2020;12:1808–21.

  27. Steinhauer W, Hoogenboom R, Keul H, Moeller M. Copolymerization of 2-hydroxyethyl acrylate and 2-methoxyethyl acrylate via raft: Kinetics and thermoresponsive properties. Macromolecules. 2010;43:7041–7.

    Article  CAS  Google Scholar 

  28. Hoogenboom R, Zorn AM, Keul H, Barner-Kowollik C, Moeller M. Copolymers of 2-hydroxyethylacrylate and 2-methoxyethyl acrylate by nitroxide mediated polymerization: Kinetics, sec-esi-ms analysis and thermoresponsive properties. Polym Chem. 2012;3:335–42.

    Article  CAS  Google Scholar 

  29. Li B, Yuan Z, Hung HC, Ma J, Jain P, Tsao C, et al. Revealing the immunogenic risk of polymers. Angew Chem Int Ed. 2018;57:13873–6.

    Article  CAS  Google Scholar 

  30. Strobl GR, Schneider M. Direct evaluation of the electron density correlation function of partially crystalline polymers. J Polym Sci Polym Phys Ed. 1980;18:1343–59.

    Article  CAS  Google Scholar 

  31. Vonk CG, Kortleve G. X-ray small-angle scattering of bulk polyethylene. Colloid Polym Sci. 1967;220:19–24.

    CAS  Google Scholar 

  32. Jesson CP, Pearce CM, Simon H, Werner A, Cunningham VJ, Lovett JR, et al. H2O2 enables convenient removal of raft end-groups from block copolymer nano-objects prepared via polymerization-induced self-assembly in water. Macromolecules. 2017;50:182–91.

    Article  CAS  PubMed  Google Scholar 

  33. Morita S, Tanaka M, Ozaki Y. Time-resolved in situ ATR-IR observations of the process of sorption of water into a poly(2-methoxyethyl acrylate) film. Langmuir. 2007;23:3750–61.

    Article  CAS  PubMed  Google Scholar 

  34. Nishida K, Nishimura SN, Tanaka M. Selective accumulation to tumor cells with coacervate droplets formed from a water-insoluble acrylate polymer. Biomacromolecules. 2022;23:1569–80.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by JSPS KAKENHI Grant Number JP22H02147 (Grant-in-Aid for Scientific Research (B)) and JP22H04555, JP19H05714, JP19H05720 (Grant-in-Aid for Scientific Research on Innovative Area: Aquatic Functional Materials). YH acknowledges the Toshiaki Ogasawara Memorial Foundation for its financial support. This work was performed under the Cooperative Research Program of “Network Joint Research Center for Materials and Devices”. Synchrotron SAXS experiments were performed on the BL06 and BL11 beamlines at the SAGA Light Source (proposal numbers 2022IIK013, 2211113 F). The authors acknowledge Dr. M. Kawamoto for his assistance with the SAXS measurements. The authors gratefully acknowledge Prof. Emi Hifumi (Oita University) for her help in conducting the DLS measurements. The following supplementary information is available at the Polymer Journal website: measurements; synthesis of 2-(N-(2-acryloyloxyethyl)-N,N-dimethyl)ammonio)-1-(tert-butoxy)-1-oxoethane bromide (tert-BuCBA2); 1H-NMR spectrum of P(tert-BuCBA2)-CTA and PCBA2; appearance of PMEA76, PCBA229, and PCBA229-b-PMEA199 salt-free aqueous solutions; Rh distributions of PCBA2n-b-PMEAm in 150 mM NaCl aqueous solutions; correlation function profile for the PCBA233-b-PMEA146 60 wt% salt-free aqueous solution; phase contrast optical microscopy image of the coacervate droplets in PCBA233-b-PMEA146 solutions; and SAXS data for polymer concentration-dependent PCBA229-b-PMEA34 aggregation in salt-free aqueous solutions.

Author information

Authors and Affiliations

  1. Faculty of Science and Technology, Oita University, 700 Dannoharu, Oita, 870-1192, Japan

    Yuji Higaki & Honoka Toyama

  2. Graduate School of Engineering, Oita University, 700 Dannoharu, Oita, 870-1192, Japan

    Takumi Masuda

  3. Institute for Materials Chemistry and Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka, 819-0395, Japan

    Shingo Kobayashi & Masaru Tanaka

Authors
  1. Yuji Higaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Honoka Toyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Takumi Masuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shingo Kobayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Masaru Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yuji Higaki.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

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

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Higaki, Y., Toyama, H., Masuda, T. et al. Microphase separation of double-hydrophilic poly(carboxybetaine acrylate)-poly(2-methoxyethyl acrylate) block copolymers in water. Polym J 55, 1357–1365 (2023). https://doi.org/10.1038/s41428-023-00831-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41428-023-00831-3

Search

Advanced search

Quick links