Skip to main content
SpringerLink
Log in

Thermo- and pH-sensitive Polymer with Pendant Spacer-linked Imidazole Cycles

  • Research Article
  • Published:
Chinese Journal of Polymer Science Aims and scope Submit manuscript

Abstract

By the reaction of poly(acryloyl chloride) with N-(3-aminopropyl)imidazole, poly(N-(3-(1H-imidazol-1-yl)propyl)acrylamide) was synthesized. The new polymer contains an imidazole ring removed from the main chain by a spacer of five bonds. The structure and purity, molecular weight, hydrodynamic and thermosensitive properties of the obtained sample were studied by 1H- and 13C-NMR, FTIR spectroscopy, acid-base titration, light scattering, turbidimetry and viscometry. The observed ability of the imidazole-containing polymer to form and destroy associates in water-salt solutions at pH 6.6–7.4 and temperatures of 29–48 °C indicates that these are promising candidates for designing complex biomedical systems. The new polymer is able to form complexes with oligo-DNA more actively than poly(1-vinylimidazole), which is of interest for gene delivery applications. The polymer cross-linked with epichlorohydrin gives micro-relief coatings on the plastic surface, and the modified surface is able to attach negatively charged objects. This thermo- and pH-sensitive polymer modification can be applied to create finely controlled surfaces for cell culturing.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Wei, M.; Gao, Y.; Li, X.; Serpe, M. J. Stimuli-responsive polymers and their applications. Polym. Chem., 2017, 8, 127–143.

    Article  CAS  Google Scholar 

  2. Cabane, E.; Zhang, X.; Langowska, K.; Palivan, C. G.; Meier, W. Stimuli-responsive polymers and their applications in nanomedicine. Biointerphases, 2012, 7, 9.

    Article  CAS  PubMed  Google Scholar 

  3. Bawa, P.; Pillay, V.; E Choonara, Y.; Toit, L. C. Stimuli-responsive polymers and their applications in drug delivery. Biomed. Mater., 2009, 4, 022001.

    Article  ADS  PubMed  Google Scholar 

  4. Gandhi, A.; Paul, A.; Sen, S. O.; Sen, K. K. Studies on thermoresponsive polymers: Phase behaviour, drug delivery and biomedical applications. Asian J. Pharm. Sci., 2015, 10, 99–107.

    Article  Google Scholar 

  5. Kocak, G.; Tuncer, C.; Bütün, V. pH-Responsive polymers. Polym. Chem., 2017, 8, 144–176.

    Article  CAS  Google Scholar 

  6. Ward, M. A.; Georgiou, T. K. Thermoresponsive polymers for biomedical applications. Polymers, 2011, 3, 1215–1242.

    Article  CAS  Google Scholar 

  7. Simonova, M. A.; Zakharova, N. V.; Khayrullin, A. R.; Filippov, A. P.; Annenkov, V. V. Behavior of double stimuli-responsive copolymer of N(3-(diethylamino)propyl)-N-methylacrylamide and N-N-diethylacrylamide in aqueous solutions. Int. J. Polym. Anal. Charact., 2018, 23, 236–243.

    Article  CAS  Google Scholar 

  8. Zakharova, N. V.; Simonova, M. A.; Filippov, A. P.; Zelinskiy, S. N.; Annenkov, V. V. Synthesis, molecular characteristics, and stimulus-sensitivity of graft-copolymer of chitosan poly(N,N-diethylacrylamide). J. Molecular Liq., 2019, 292, 111355.

    Article  Google Scholar 

  9. Pilipenko, I. M.; Korzhikov-Vlakh, V. A.; Zakharova, N. V.; Tennikova, T. B.; Urtti, A. Thermo- and pH-sensitive glycosaminoglycans derivatives obtained by controlled grafting of poly(N-isopropylacrylamide). Carbohydr. Polym., 2020, 248, 116764.

    Article  CAS  PubMed  Google Scholar 

  10. Kyriakides, T.; Cheung, C.; Murthy, N., Bornstein, P.; Stayton, P.; Hoffman, A. J. pH-Sensitive polymers that enhance intracellular drug delivery in vivo. Control. Rel., 2002, 78, 295–303.

    Article  CAS  Google Scholar 

  11. Drummond, D.; Zignani, M.; Leroux, J. Current status of pH-sensitive liposomes in drug delivery. Prog. Lipid Res., 2000, 39, 409–460.

    Article  CAS  PubMed  Google Scholar 

  12. Durfresne, M.; Garrec, D.; Sant, V.; Leroux, J.; Ranger, M. Preparation and characterization of water-soluble pH-sensitive nanocarriers for drug delivery. Int. J. Pharmaceutics, 2004, 277, 81–90.

    Article  Google Scholar 

  13. Gerasimov, O.; Boomer J.; Qualls M.; Thompson D. Cytosolic drug delivery using pH- and light-sensitive liposomes. Adv. Drug Deliv. Rev., 1999, 38, 317–338.

    Article  CAS  PubMed  Google Scholar 

  14. Liu, D.; Sun, J. Thermoresponsive Polypeptoids. Polymers, 2020, 12, 2973.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Zhang, Y.; Broekhuis, A. A.; Stuart, M. C. A.; Picchioni, F. Polymeric amines by chemical modifications of alternating aliphatic polyketones. J. Appl. Polym. Sci., 2008, 107, 262–271.

    Article  CAS  Google Scholar 

  16. Bütün, V.; Weaver, J. V. M.; Bories-Azeau, X.; Cai, Y.; Armes, S. P. A brief review of ‘schizophrenic’ block copolymers. React. Funct. Polym., 2006, 66, 157–165.

    Article  Google Scholar 

  17. Smedt, S. C. D.; Demeester, J.; Hennink, W. E. Cationic polymer based gene delivery systems. Pharm. Res., 2000, 17, 113–126.

    Article  PubMed  Google Scholar 

  18. Allen, M. H. Jr.; Day, K. N.; Hemp, S. T.; Long, T. E. Synthesis of folic acid-containing imidazolium copolymers for potential gene delivery applications. Macromol. Chem. Phys., 2013, 214, 797–805.

    Article  CAS  Google Scholar 

  19. Danilovtseva, E. N.; Krishnan, U. M.; Pal’shin, V. A.; Annenkov, V. V. Polymeric amines and ampholytes derived from poly(acryloyl chloride): synthesis, influence on silicic acid condensation and interaction with nucleic acid. Polymers, 2017, 9, 624.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Ofridam, F.; Tarhini, M.; Lebaz, N.; Gagnière, É.; Mangin, D.; Elaissari, A. pH-sensitive polymers: classification and some fine potential applications. Polym. Adv. Technol. 2021, 32, 1455–1484.

    Article  CAS  Google Scholar 

  21. Oda, Y.; Kanaoka, S.; Aoshima, S. Synthesis of dual pH/temperature-responsive polymers with amino groups by living cationic polymerization. J. Polym. Sci, Part A: Polym. Chem., 2010, 4, 1207–1213.

    Article  ADS  Google Scholar 

  22. Gil, E. S.; Hudson, S. M. Stimuli- responsive polymers and their bioconjugate. Prog. Polym. Sci., 2004, 29, 1173–1222.

    Article  CAS  Google Scholar 

  23. SPARC. pKa/property server. Ver 4.2 Mar. 2008. Available from, as of October 28, 2009: https://ibmlc2.chem.uga.edu/sparc/.

  24. Albert, A. Heterocyclic chemistry. 2nd Ed.; Athlone Press, 1968.

  25. Sundberg, R. J.; Martin, R. B. Interactions of histidine and other imidazole derivatives with transition metal ions in chemical and biological systems. Chem. Rev., 1974, 74, 471–517.

    Article  CAS  Google Scholar 

  26. Nozaki, Y.; Gurd, F. R. N.; Chen, R. F.; Edsall, J. T. The association of 4-methylimidazole with the ions of cupric copper and zinc; with some observations on 2,4-dimethylimidazole. J. Am. Chem. Soc., 1957, 79, 2123–2129.

    Article  CAS  Google Scholar 

  27. Pozdnyakov, A. S.; Emel’yanov, A. I.; Korzhova, S. A.; Kuznetsova, N. P.; Bolgova, Y. I.; Trofimova, O. M.; Semenova, T. A.; Prozorova, G. F. Green synthesis of stable nanocomposites containing copper nanoparticles incorporated in poly-N-vinylimidazole. Polymers, 2021, 13, 3212.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Luo, X. F.; Goh, S. H.; Lee, S. Y. Miscibility and interpolymer complexation of poly(1-vinylimidazole) with hydroxyl- and carboxyl-containing polymers. Makromol. Chem. Phys., 1999, 200, 399–404.

    Article  CAS  Google Scholar 

  29. Isikli, S.; Tuncagil, S.; Bozkurt, A.; Toppare, L. Immobilization of invertase in a novel proton conducting poly(vinylphosphonic acid—poly(1-vinylimidazole) network. J. Macromol. Sci. Part A, 2010, 47, 639–646.

    Article  CAS  Google Scholar 

  30. Asayama, S.; Nishinohara, S.; Kawakami, H. Zinc-chelated poly(1-vinylimidazole) and a carbohydrate ligand polycation form DNA ternary complexes for gene delivery. Bioconjugate Chem., 2011, 22, 1864–1868.

    Article  CAS  Google Scholar 

  31. Danilovtseva, E. N.; Zelinskiy, S. N.; Pal’shin, V. A.; Kandasamy, G.; Krishnan, U. M.; Annenkov, V. V. Poly(1-vinylimidazole) prospects in gene delivery. Chinese J. Polym. Sci., 2019, 37, 637–645.

    Article  Google Scholar 

  32. Mazyar, N. L.; Annenkov, V. V.; Kruglova, V. A.; Ananiev, S. M.; Danilovtseva, E. N.; Rokhin, A. V.; Zinchenko, S. V. Acid-base properties of poly(1-vinylazoles) in aqueous solution. Rus. Chem. Bull. Intern. Ed., 2000, 49, 2013–2017.

    Article  CAS  Google Scholar 

  33. Sharma, A.; Srivastava, A. Pronounced influence of pH, metal-ion and solvent isotope on the thermoresponse of synthetic amphiphilic polypeptides. Polym. Chem., 2013, 4, 5119–5128.

    Article  CAS  Google Scholar 

  34. Seo, K.; Kim, D. Phase transition behavior of novel pH-sensitive polyaspartamide derivatives grafted with 1-(3-aminopropyl)imidazole. Macromol. Biosci., 2006, 6, 758–766.

    Article  CAS  PubMed  Google Scholar 

  35. Bogomolova, A.; Kaberov, L.; Sedlacek, O.; Filippov, S. K.; Stepanek, P.; Král, V.; Wang, X. Y.; Liu, S. L.; Ye, X. D.; Hruby, M. Double stimuli-responsive polymer systems: how to use crosstalk between pH- and thermosensitivity for drug depots. Eur. Polym. J., 2016, 84, 54–64.

    Article  CAS  Google Scholar 

  36. Naka, K.; Masuoka, S.; Shinke, R.; Yamada, M. Synthesis of first-and second-generation imidazoleterminated POSS-core dendrimers and their pH responsive and coordination properties. Polym. J., 2012, 44, 353–359.

    Article  CAS  Google Scholar 

  37. Handel, T. M.; Ponticello, I. S.; Tan, J. S. Effects of side-chain structure on polymer conformation: synthesis and dilute solution properties. Macromolecules, 1987, 20, 264–267.

    Article  ADS  CAS  Google Scholar 

  38. Zakharova, N. V.; Filippov, A. P.; Zelinskii, S. N.; Danilovtseva, E. N.; Annenkov, V. V. The influence of composition of thermo- and pH-sensitive copolymers of N-(3-(hiethylnmipo)propyl)-N-methylacrylamide and N, N-diethylacrylamide on their behavior in aqueous solutions. Polym. Sci. A, 2019, 61, 1–8.

    Article  CAS  Google Scholar 

  39. Annenkov, V. V.; Danilovtseva, E. N.; Zelinskiy, S. N.; Basharina, T. N.; Safonova, T. A.; Korneva, E. S.; Likhoshway, Ye. V.; Grachev, M. A. Novel fluorescent dyes based on oligopropylamines for the in vivo staining of eukaryotic unicellular algae. Anal. Biochem., 2010, 407, 44–51.

    Article  CAS  PubMed  Google Scholar 

  40. Annenkov, V. V.; Danilovtseva, E. N.; Likhoshway, Y. V.; Patwardhan, S. V.; Perry C. C. Controlled stabilisation of silicic acid below pH 9 using poly(1-vinylimidazole). J. Mater. Chem., 2008, 18, 553–559.

    Article  CAS  Google Scholar 

  41. Buruiana, E.C.; Buruiana, T.; Hahui, L. Preparation and characterization of new optically active poly(N-acryloyl chloride) functionalized with (S)-phenylalanine and pendant pyrene. J. Photochem. Photobiol. A, 2007, 189, 65–72.

    Article  CAS  Google Scholar 

  42. Sandeli, E. B.; West, T. S. Recommended nomenclature for titrimetric analysis. Pure Appl. Chem., 1969, 18, 427–436.

    Article  Google Scholar 

  43. Danilovtseva, E. N.; Verkhozina, O. N.; Zelinskiy, S. N.; Ivanov, N. A.; Tsiganov, P.Y.; Basharina, T. N.; Annenkov, V. V. New fluorescent derivatives of oligopropylamines. ARKIVOC, 2013, 3, 266–281.

    Article  Google Scholar 

  44. González-de-Castro, Á.; Broughton, H.; Martínez-Pérez, J. A.; Espinosa, J. F. Conformational features of secondary N-cyclopropyl amides. J. Org. Chem., 2015, 80, 3914–3920.

    Article  PubMed  Google Scholar 

  45. Lanyon-Hogg, T.; Ritzefeld, M.; Masumoto, N.; Magee, A. I.; Rzepa, H. S.; Tate, E. W. Modulation of amide bond rotamers in 5-acyl-6,7-dihydrothieno[3,2-c]pyridines. J. Org. Chem., 2015, 80, 4370–4377.

    Article  CAS  PubMed  Google Scholar 

  46. Lippert, J. L.; Robertson, J. A.; Havens, J. R.; Tan, J. S. Structural studies of poly(N-vinylimidazole) complexes by infrared and Raman spectroscopy. Macromolecules, 1985, 18, 63–67.

    Article  ADS  CAS  Google Scholar 

  47. Katchalsky, A.; Mazur, J.; Spitnik, P. SECTION II: General behavior of biocolloids and polyelectrolytes in solution (continued) polybase properties of polyvinylamine. J. Polym. Sci., 1957, 23, 513–532.

    Article  ADS  CAS  Google Scholar 

  48. Nekrasova, T. N.; Gabrielyan, A. G.; Ptitsyn, O. B. Determination of the thermodynamic characteristics of the conformational transition in polymethacrylic acid from potentiometric titration curves. Polym. Sci. U.S.S.R., 1968, 10, 348–355.

    Article  Google Scholar 

  49. Kratochvil, P. in Classical light scattering from polymer solutions. Elsevier: Amsterdam, The Netherlands, 1987, 334.

    Google Scholar 

  50. Schartl, W. in Light scattering from polymer solutions and nanoparticle dispersions. Springer: Berlin, Germany, 2007, 175.

    Google Scholar 

  51. Amirova, A. I.; Dudkina, M. M.; Tenkovtsev, A. V.; Filippov, A. P. Self-assembly of star-shaped poly(2-isopropyl-2-oxazoline) in aqueous solutions. Colloid. Polym. Sci., 2015, 293, 239–248.

    Article  CAS  Google Scholar 

  52. Filippov, A. P.; Tarabukina, E. B.; Zakharova, N. V.; Amirova, A. I.; Simonova, M. A. Behaviorial features of aqueous solutions of thermoresponsive and pH-sensitive polymers with complicated architectures. Fiber Chem., 2015, 47, 137–143.

    Article  CAS  Google Scholar 

  53. Annenkov, V. V.; Krishnan, U. M.; Pal’shin, V. A.; Zelinskiy, S. N.; Kandasamy, G.; Danilovtseva, E. N. Design of oligonucleotide carriers: importance of polyamine chain length. Polymess, 2018, 10, 1297.

    Google Scholar 

  54. Boussif, O.; Lezoualc’h, F.; Zanta, M. A.; Mergny, M. D.; Scherman, D. A.; Demeneix, B.; Behr, J. P. A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine. Proc. Natl. Acad. Sci. U. S. A., 1955, 92, 7297–7301.

    Article  ADS  Google Scholar 

  55. Hu, X.; Li, Y.; Liu, T.; Zhang, G.; Liu, S. Photodegradable neutral-cationic brush block copolymers for nonviral gene delivery. Chem. Asian J., 2014, 9, 2148–2155.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was financially supported by the Russian Science Foundation (No. 22-24-00474).

Author information

Authors and Affiliations

  1. Institute of Macromolecular Compounds of the Russian Academy of Sciences, Saint Petersburg, 199004, Russia

    Natalya V. Zakharova

  2. Limnological Institute of Siberian Branch of the Russian Academy of Sciences, Irkutsk, 664033, Russia

    Stanislav N. Zelinskiy, Mariya S. Strelova, Elena N. Danilovtseva & Vadim V. Annenkov

Authors
  1. Natalya V. Zakharova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stanislav N. Zelinskiy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mariya S. Strelova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Elena N. Danilovtseva
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Vadim V. Annenkov
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Natalya V. Zakharova.

Ethics declarations

The authors declare no interest conflict.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zakharova, N.V., Zelinskiy, S.N., Strelova, M.S. et al. Thermo- and pH-sensitive Polymer with Pendant Spacer-linked Imidazole Cycles. Chin J Polym Sci 42, 437–445 (2024). https://doi.org/10.1007/s10118-023-3056-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10118-023-3056-6

Keywords

Search

Navigation