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Isolation of hetero-telechelic polyethylene glycol with groups of different reactivity at the chain ends

Polymer Journal volume 54, pages 1321–1329 (2022)Cite this article

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Abstract

Hetero-telechelic polymers (HTPs) with different reactive functional groups at the chain ends, which can react selectively with other molecules or surfaces to form new chemical bonds, are attractive in the context of reaction selectivity and elaborate polymer modification. However, effective synthetic routes to HTPs remain limited, especially those based on postpolymerization modification processes. Herein, we report a versatile method based on reversed-phase column chromatography for separation of modified poly(ethylene glycol) with a hydroxy group and a maleimide–furan adduct at its α and ω ends. Protection of the maleimide end with furan protects the imide moiety from hydrolysis during the purification process, and the furan protecting group can be reversibly removed by heating. Furthermore, the resulting hetero-telechelic polymers were successfully applied to syntheses of block copolymers.

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References

  1. Webster OW. Living polymerization methods. Science 1991;251:887–93.

    Article  CAS  PubMed  Google Scholar 

  2. Kolb HC, Finn MG, Sharpless KB. Click chemistry: diverse chemical function from a few good reactions. Angew Chem Int. 2001;40:2004–21.

    Article  CAS  Google Scholar 

  3. Iha RK, Wooley KL, Nyström AM, Burked DJ, Kade MJ, Hawker CJ. Applications of orthogonal ‘Click’ Chemistries in the synthesis of functional soft materials. Chem Rev. 2009;109:5620–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Patten TE, Matyjaszewski K. Atom transfer radical polymerization and the synthesis of polymeric materials. Adv Mater. 1998;10:901–15.

    Article  CAS  Google Scholar 

  5. Willcock H, O’Reilly RK. End group removal and modification of RAFT polymers. Polym Chem. 2010;1:149–57.

    Article  CAS  Google Scholar 

  6. Lo Verso F, Likos CN. End-functionalized polymers: versatile building blocks for soft materials. Polymer. 2008;49:1425–34.

    Article  CAS  Google Scholar 

  7. Zhou D, Zhu L-W, Wu B-H, Xu Z-K, Wan L-S. End-functionalized polymers by controlled/living radical polymerizations: synthesis and applications. Polym Chem. 2022;13:300–58.

    Article  CAS  Google Scholar 

  8. Kakuchi R, Theato P. Sequential post-polymerization modification reactions of poly(pentafluorophenyl 4-vinylbenzenesulfonate). Polym Chem. 2014;5:2320.

    Article  CAS  Google Scholar 

  9. Hamaguchi K, Ichikawa R, Kajiyama S, Torii S, Hayashi Y, Kumaki J, et al. Gemini thermotropic smectic liquid crystals for two-dimensional nanostructured water-treatment membranes. ACS Appl Mater Interfaces. 2021;13:20598–605.

    Article  CAS  PubMed  Google Scholar 

  10. Yanagisawa Y, Nan Y, Okuro K, Aida T. Mechanically robust, readily repairable polymers via tailored noncovalent cross-linking. Science. 2018;359:72–76.

    Article  CAS  PubMed  Google Scholar 

  11. Wang Y, Quinsaat JEQ, Ono T, Maeki M, Tokeshi M, Isono T, et al. Enhanced dispersion stability of gold nanoparticles by the physisorption of cyclic poly(ethylene glycol). Nat Commun. 2020;11:6089.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Aoki D. A rational entry to cyclic polymers via spontaneous and selective cyclization reactions. Polym J. 2021;53:257–69.

    Article  CAS  Google Scholar 

  13. Laurent BA, Grayson SM. Synthetic approaches for the preparation of cyclic polymers. Chem Soc Rev. 2009;38:2202.

    Article  CAS  PubMed  Google Scholar 

  14. Schulz M, Tanner S, Barqawi H, Binder WH. Macrocyclization of polymers via ring-closing metathesis and azide/alkyne- ‘click’ -reactions: an approach to cyclic polyisobutylenes. J Polym Sci Part A Polym Chem. 2010;48:671–80.

    Article  CAS  Google Scholar 

  15. Sun H, Kabb CP, Sims MB, Sumerlin BS. Architecture-transformable polymers: reshaping the future of stimuli-responsive polymers. Prog Polym Sci. 2019;89:61–75.

    Article  CAS  Google Scholar 

  16. Sato H, Aoki D, Marubayashi H, Uchida S, Sogawa H, Nojima S, et al. Topology-transformable block copolymers based on a rotaxane structure: change in bulk properties with same composition. Nat Commun. 2021;12:6175.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Honda S, Yamamoto T, Tezuka Y. Tuneable enhancement of the salt and thermal stability of polymeric micelles by cyclized amphiphiles. Nat Commun. 2013;4:1574.

    Article  PubMed  Google Scholar 

  18. Honda S, Toyota T. Photo-triggered solvent-free metamorphosis of polymeric materials. Nat Commun. 2017;8:502.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Ree BJ, Satoh Y, Isono T, Satoh T. Influence of topological confinement on nanoscale film morphologies of tricyclic block copolymers. Macromolecules. 2021;54:4120–7.

    Article  CAS  Google Scholar 

  20. Muramatsu Y, Takasu A. Synthetic innovations for cyclic polymers. Polym J. 2022;54:121–32.

    Article  CAS  Google Scholar 

  21. Shibayama M. Structure-mechanical property relationship of tough hydrogels. Soft Matter. 2012;8:8030.

    Article  CAS  Google Scholar 

  22. Gong JP. Why are double network hydrogels so tough? Soft Matter. 2010;6:2583.

    Article  CAS  Google Scholar 

  23. Noda Y, Hayashi Y, Ito K. From topological gels to slide‐ring materials. J Appl Polym Sci. 2014;131:40509.

    Article  Google Scholar 

  24. Liu C, Morimoto N, Jiang L, Kawahara S, Noritomi T, Yokoyama H, et al. Tough hydrogels with rapid self-reinforcement. Science. 2021;372:1078–81.

    Article  CAS  PubMed  Google Scholar 

  25. Sakai T, Matsunaga T, Yamamoto Y, Ito C, Yoshida R, Suzuki S, et al. Design and fabrication of a high-strength hydrogel with ideally homogeneous network structure from tetrahedron-like macromonomers. Macromolecules. 2008;41:5379–84.

    Article  CAS  Google Scholar 

  26. Bin Imran A, Esaki K, Gotoh H, Seki T, Ito K, Sakai Y, et al. Extremely stretchable thermosensitive hydrogels by introducing slide-ring polyrotaxane cross-linkers and ionic groups into the polymer network. Nat Commun. 2014;5:5124.

    Article  Google Scholar 

  27. Park J, Murayama S, Osaki M, Yamaguchi H, Harada A, Matsuba G, et al. Extremely rapid self‐healable and recyclable supramolecular materials through planetary ball milling and host–guest interactions. Adv Mater. 2020;32:2002008.

    Article  CAS  Google Scholar 

  28. Fujiyabu T, Sakumichi N, Katashima T, Liu C, Mayumi K, Chung U, et al. Tri-branched gels: rubbery materials with the lowest branching factor approach the ideal elastic limit. Sci Adv. 2022;8:1–10.

    Article  Google Scholar 

  29. Haag R, Kratz F. Polymer therapeutics: concepts and applications. Angew Chem Int. 2006;45:1198–215.

    Article  CAS  Google Scholar 

  30. Roth PJ, Jochum FD, Zentel R, Theato P. Synthesis of hetero-telechelic α,ω bio-functionalized polymers. Biomacromolecules. 2010;11:238–44.

    Article  CAS  PubMed  Google Scholar 

  31. Tasdelen MA, Kahveci MU, Yagci Y. Telechelic polymers by living and controlled/living polymerization methods. Prog Polym Sci. 2011;36:455–567.

    Article  CAS  Google Scholar 

  32. Gauthier MA, Gibson MI, Klok HA. Synthesis of functional polymers by post-polymerization modification. Angew Chem Int. 2009;48:48–58.

    Article  CAS  Google Scholar 

  33. Herzberger J, Niederer K, Pohlit H, Seiwert J, Worm M, Wurm FR, et al. Polymerization of ethylene oxide, propylene oxide, and other alkylene oxides: synthesis, novel polymer architectures, and bioconjugation. Chem Rev. 2016;116:2170–243.

    Article  CAS  PubMed  Google Scholar 

  34. Pohlit H, Worm M, Langhanki J, Berger-Nicoletti E, Opatz T, Frey H. Silver oxide mediated monotosylation of poly(ethylene glycol) (PEG): heterobifunctional PEG via polymer desymmetrization. Macromolecules. 2017;50:9196–206.

    Article  CAS  Google Scholar 

  35. Nagasaki Y, Kutsuna T, Iijima M, Kato M, Kataoka K, Kitano S, et al. Formyl-ended heterobifunctional poly(ethylene oxide): synthesis of poly(ethylene oxide) with a formyl group at one end and a hydroxyl group at the other end. Bioconjug Chem. 1995;6:231–3.

    Article  CAS  PubMed  Google Scholar 

  36. Ishii T, Yamada M, Hirase T, Nagasaki Y. New synthesis of heterobifunctional poly(ethylene glycol) possessing a pyridyl disulfide at one end and a carboxylic acid at the other end. Polym J. 2005;37:221–8.

    Article  CAS  Google Scholar 

  37. Arai T, Jang K, Koyama Y, Asai S, Takata T. Versatile supramolecular cross-linker: a rotaxane cross-linker that directly endows vinyl polymers with movable cross-links. Chem - A Eur J. 2013;19:5917–23.

    Article  CAS  Google Scholar 

  38. Jang K, Iijima K, Koyama Y, Uchida S, Asai S, Takata T. Synthesis and properties of rotaxane-cross-linked polymers using a double-stranded γ-CD-based inclusion complex as a supramolecular cross-linker. Polymer. 2017;128:379–85.

    Article  CAS  Google Scholar 

  39. Mizutani N, Hosono N, Le Ouay B, Kitao T, Matsuura R, Kubo T, et al. Recognition of polymer terminus by metal-organic frameworks enabling chromatographic separation of polymers. J Am Chem Soc. 2020;142:3701–5.

    Article  CAS  PubMed  Google Scholar 

  40. Wei Y, Zhuo R, Jiang X. Separation of polyethylene glycols and maleimide-terminated polyethylene glycols by reversed-phase liquid chromatography under critical conditions. J Sep Sci. 2016;39:4305–13.

    Article  CAS  PubMed  Google Scholar 

  41. Wei YZ, Zhuo RX, Jiang XL. Separation of polyethylene glycols and amino-terminated polyethylene glycols by high-performance liquid chromatography under near critical conditions. J Chromatogr A. 2016;1447:122–8.

    Article  CAS  PubMed  Google Scholar 

  42. Wei YZ, Chu YF, Uliyanchenko E, Schoenmakers PJ, Zhuo RX, Jiang XL. Separation and characterization of benzaldehyde-functional polyethylene glycols by liquid chromatography under critical conditions. Polym Chem. 2016;7:7506–13.

    Article  CAS  Google Scholar 

  43. Annunziato ME, Patel US, Ranade M, Palumbo PS. P-maleimidophenyl isocyanate: a novel heterobifunctional linker for hydroxyl to thiol coupling. Bioconjug Chem. 1993;4:212–8.

    Article  CAS  PubMed  Google Scholar 

  44. Takashima R, Kida J, Aoki D, Otsuka H. Maleimidophenyl isocyanates as postpolymerization modification agents and their applications in the synthesis of block copolymers. J Polym Sci Part A Polym Chem. 2019;57:2396–406.

    Article  CAS  Google Scholar 

  45. Takashima R, Ohira M, Yokochi H, Aoki D, Li X, Otsuka H. Characterization of N -phenylmaleimide-terminated poly(ethylene glycol)s and their application to a tetra-arm poly(ethylene glycol) gel. Soft Matter. 2020;16:10869–75.

    Article  CAS  PubMed  Google Scholar 

  46. Makiguchi K, Satoh T, Kakuchi T. Diphenyl phosphate as an efficient cationic organocatalyst for controlled/living ring-opening polymerization of δ-valerolactone and ε-caprolactone. Macromolecules. 2011;44:1999–2005.

    Article  CAS  Google Scholar 

  47. Ray WJ, Puvathingal JM. A simple procedure for removing contaminating aldehydes and peroxides from aqueous solutions of polyethylene glycols and of nonionic detergents that are based on the polyoxyethylene linkage. Anal Biochem. 1985;146:307–12.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This research was supported by the AGC Research Collaboration, trust research/joint research funds from the Asahi Kasei Corporation, and the Fujikura Foundation.

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Authors and Affiliations

  1. Department of Chemical Science and Engineering, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo, 152-8550, Japan

    Tatsuki Sato, Rikito Takashima & Hideyuki Otsuka

  2. Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba-shi, Chiba, 263-8522, Japan

    Daisuke Aoki

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  1. Tatsuki Sato
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Correspondence to Daisuke Aoki or Hideyuki Otsuka.

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Sato, T., Takashima, R., Aoki, D. et al. Isolation of hetero-telechelic polyethylene glycol with groups of different reactivity at the chain ends. Polym J 54, 1321–1329 (2022). https://doi.org/10.1038/s41428-022-00676-2

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  • DOI: https://doi.org/10.1038/s41428-022-00676-2

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