Chemical Research in Chinese Universities

, Volume 35, Issue 5, pp 929–936 | Cite as

Synthesis of PEGylated Salicylaldehyde Azine via Metal-free Click Chemistry for Cellular Imaging Applications

  • Xin Chen
  • Chunsheng XiaoEmail author
  • Xuesi ChenEmail author


In this work, two kinds of PEGylated salicylaldehyde azine(SA) polymers were prepared and investigated for cellular imaging applications. First, a diazido derivative of SA was synthesized and subsequently PEGylated with polyethylene glycol monomethyl ether(mPEG) by metal-free azide-alkyne 1,3-dipolar cycloaddition reaction. The formed triazole group in mPEG-SA was then converted into cationic triazolium group by N-alkylation reaction. Both the synthesized polymers, mPEG-SA and N-alkylated mPEG-SA, showed good dispersibility in water, but differences in self-assembly of nanostructures. The mPEG-SA with triazole groups self-assembled into micelles, while the N-alkylated mPEG-SA with triazolium groups self-assembled into vesicles. Furthermore, mPEG-SA and N-alkylated mPEG-SA nanoparticles showed bright fluorescence due to the aggregation of AIE-active SA molecules in the nano-particles and could be successfully used as fluorescent nanoprobes for bioimaging applications in HeLa cancer cells. Finally, both the synthesized polymers showed minimal cytotoxicity and low hemolytic activity. Therefore, these PEGylated SA polymers proved to be promising bioimaging nanoprobes or traceable drug delivery vehicles.


Click chemistry Aggregation-induced emission nanoprobe PEGylation Bioimaging Self-assembly 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Supplementary material

40242_2019_9077_MOESM1_ESM.pdf (662 kb)
Synthesis of PEGylatedSalicylaldehydeAzinevia Metal-free ClickChemistry for Cellular Imaging Applications


  1. [1]
    Kolb H. C., Finn M. G., Sharpless K. B., Angew. Chem. Int. Edit., 2001, 40(11), 2004CrossRefGoogle Scholar
  2. [2]
    Kolb H. C., Sharpless K. B., Drug Discov. Today, 2003, 8(24), 1128CrossRefPubMedGoogle Scholar
  3. [3]
    Espeel P., Du Prez F. E., Macromolecules, 2015, 48(1), 2CrossRefGoogle Scholar
  4. [4]
    Wu P., Feldman A. K., Nugent A. K., Hawker C. J., Scheel A., Voit B., Pyun J., Frechet J. M. J., Sharpless K. B., Fokin V. V., Angew. Chem. Int. Edit., 2004, 43(30), 3928CrossRefGoogle Scholar
  5. [5]
    Tornoe C. W., Christensen C., Meldal M., J. Org. Chem., 2002, 67(9), 3057CrossRefPubMedPubMedCentralGoogle Scholar
  6. [6]
    Speers A. E., Cravatt B. F., Chem. Biol., 2004, 11 (4), 535CrossRefPubMedGoogle Scholar
  7. [7]
    Thirumurugan P., Matosiuk D., Jozwiak K., Chem. Rev., 2013, 113(7), 4905CrossRefPubMedPubMedCentralGoogle Scholar
  8. [8]
    Zhang Y., Ding J. X., Li M. Q., Chen X., Xiao C. S., Zhuang X. L., Huang Y. B., Chen X. S., ACS Appl. Mater. Inter., 2016, 8(17), 10673CrossRefGoogle Scholar
  9. [9]
    Liu Z., Wang Y., Sun J., Yang Y., Liu Q., Liu Z., Song Z., Chem. Res. Chinese Universities, 2015, 31(4), 526CrossRefGoogle Scholar
  10. [10]
    Fournier D., Hoogenboom R., Schubert U. S., Chem. Soc. Rev., 2007, 36(8), 1369CrossRefPubMedGoogle Scholar
  11. [11]
    Golas P. L., Matyjaszewski K., Chem. Soc. Rev., 2010, 39(4), 1338CrossRefGoogle Scholar
  12. [12]
    Sun R., Wang Y., Gou P., Zuo M., Li X., Zhu W., Shen Z., Chem. Res. Chinese Universities, 2018, 34(1), 132CrossRefGoogle Scholar
  13. [13]
    Hong V., Presolski S. I., Ma C., Finn M. G., Angew. Chem. Int. Edit., 2009, 48(52), 9879CrossRefGoogle Scholar
  14. [14]
    Shi H., Kwok R. T., Liu J., Xing B., Tang B. Z., Liu B., J. Am. Chem. Soc., 2012, 134(43), 17972CrossRefPubMedGoogle Scholar
  15. [15]
    Lutz J. F., Angew. Chem. Int. Edit., 2008, 47(12), 2182CrossRefGoogle Scholar
  16. [16]
    Baskin J. M., Prescher J. A., Laughlin S. T., Agard N. J., Chang P. V., Miller I. A., Lo A., Codelli J. A., Bertozzi C. R., Proc. Natl. Acad. Sci. USA, 2007, 104(43), 16793CrossRefPubMedGoogle Scholar
  17. [17]
    Chan T. R., Hilgraf R., Sharpless K. B., Fokin V. V., Org. Lett., 2004, 6(17), 2853CrossRefPubMedPubMedCentralGoogle Scholar
  18. [18]
    Shi Y., Graff R. W., Cao X., Wang X., Gao H., Angew. Chem. Int. Edit., 2015, 54(26), 7631CrossRefGoogle Scholar
  19. [19]
    Agard N. J., Prescher J. A., Bertozzi C. R., J. Am. Chem. Soc., 2004, 126(46), 15046CrossRefPubMedGoogle Scholar
  20. [20]
    Clark M., Kiser P., Polym. Int., 2009, 58(10), 1190CrossRefGoogle Scholar
  21. [21]
    Li Z., Seo T. S., Ju J., Tetrahedron Lett., 2004, 45(15), 3143CrossRefGoogle Scholar
  22. [22]
    Wang Q., Chen M., Yao B., Wang J., Mei J., Sun J. Z., Qin A., Tang B. Z., Macromol. Rapid. Comm., 2013, 34(9), 796CrossRefGoogle Scholar
  23. [23]
    Qin A., Jim C. K. W., Lu W., Lam J. W. Y., Häussler M., Dong Y., Sung H. H. Y., Williams I. D., Wong G. K. L., Tang B. Z., Macromolecules, 2007, 40(7), 2308CrossRefGoogle Scholar
  24. [24]
    Li H., Wu H., Zhao E., Li J., Sun J. Z., Qin A., Tang B. Z., Macromolecules, 2013, 46(10), 3907CrossRefGoogle Scholar
  25. [25]
    Qin A., Liu Y., Tang B. Z., Macromol. Chem. Phys., 2015, 216(8), 818CrossRefGoogle Scholar
  26. [26]
    Yuan W., Chi W., Liu R., Li H., Li Y., Tang B. Z., Macromol. Rapid. Comm., 2017, 38(5), 1600745CrossRefGoogle Scholar
  27. [27]
    Li H., Mei J., Wang J., Zhang S., Zhao Q., Wei Q., Qin A., Sun J., Tang B. Z., Sci. China Chem., 2011, 54(4), 611CrossRefGoogle Scholar
  28. [28]
    Wei Q., Wang J., Shen X., Zhang X. A., Sun J. Z., Qin A., Tang B. Z., Sci. Rep., 2013, 3, 1Google Scholar
  29. [29]
    Zhou J., Lu W., Hu F., Zhang M., Jiang L., Shen Z., J. Polym. Sci. Pol. Chem., 2014, 52(16), 2248CrossRefGoogle Scholar
  30. [30]
    Alexandrino E. M., Buchold P., Wagner M., Fuchs A., Kreyes A., Weiss C. K., Landfester K., Wurm F. R., Chem. Commun., 2014, 50(72), 10495CrossRefGoogle Scholar
  31. [31]
    Agalave S. G., Maujan S. R., Pore V. S., Chem-Asian J., 2011, 6(10), 2696CrossRefPubMedGoogle Scholar
  32. [32]
    Sun J. B., Liu R. W., Xuan L. L., Leng W. C., Wu J. C., Chem. Res. Chinese Universities, 2013, 29(3), 473CrossRefGoogle Scholar
  33. [33]
    Maddili S. K., Katla R., Kannekanti V. K., Bejjanki N. K., Tuniki B., Zhou C. H., Gandham H., Eur. J. Med. Chem., 2018, 150, 228CrossRefPubMedGoogle Scholar
  34. [34]
    Koguchi S., Izawa K., Synthesis, 2012, 44(23), 3603CrossRefGoogle Scholar
  35. [35]
    Monasterio Z., Sagartzazu-Aizpurua M., Miranda J. I., Reyes Y., Aizpurua J. M., Org. Lett., 2016, 18(4), 788CrossRefPubMedGoogle Scholar
  36. [36]
    Cao Q. Y., Wang Z. C., Li M., Liu J. H., Tetrahedron Lett., 2013, 54(30), 3933CrossRefGoogle Scholar
  37. [37]
    Fletcher J. T., Sobczyk J. M., Gwazdacz S. C., Blanck A. J., Bioorg. Med. Chem. Lett, 2018, 28(20), 3320CrossRefPubMedGoogle Scholar
  38. [38]
    Shyam R., Charbonnel N., Job A., Blavignac C., Forestier C., Taillefumier C., Faure S., Chemmedchem, 2018, 13(15), 1513CrossRefPubMedGoogle Scholar
  39. [39]
    Tejero R., Lopez D., Lopez-Fabal F., Gomez-Garces J. L., Fernandez-Garcia M., Biomacromolecules, 2015, 16(6), 1844CrossRefPubMedGoogle Scholar
  40. [40]
    Elloumi A. K., Miladi I. A., Serghei A., Taton D., Aissou K., Ben Romdhane H., Drockenmuller E., Macromolecules, 2018, 51(15), 5820CrossRefGoogle Scholar
  41. [41]
    Nakabayashi K., Umeda A., Sato Y., Mori H., Polymer, 2016, 96, 81CrossRefGoogle Scholar
  42. [42]
    Lo C. T., Isawa Y., Nakabayashi K., Mori H., Eur. Polym. J., 2018, 105, 339CrossRefGoogle Scholar
  43. [43]
    Mei J., Leung N. L., Kwok R. T., Lam J. W., Tang B. Z., Chem. Rev., 2015, 115(21), 11718CrossRefPubMedGoogle Scholar
  44. [44]
    Kwok R. T., Leung C. W., Lam J. W., Tang B. Z., Chem. Soc. Rev., 2015, 44(13), 4228CrossRefPubMedGoogle Scholar
  45. [45]
    Tang W., Xiang Y., Tong A., J. Org. Chem., 2009, 74(5), 2163CrossRefPubMedGoogle Scholar
  46. [46]
    Li J., Wu J., Cui F., Zhao X., Li Y., Lin Y., Li Y., Hu J., Ju Y., Sensor Actuat. B: Chem., 2017, 243, 831CrossRefGoogle Scholar
  47. [47]
    Ma X., Cheng J., Liu J., Zhou X., Xiang H., New J. Chem., 2015, 39(1), 492CrossRefGoogle Scholar
  48. [48]
    Cui L., Baek Y., Lee S., Kwon N., Yoon J., J. Mater. Chem. C, 2016, 4(14), 2909CrossRefGoogle Scholar
  49. [49]
    Lin N., Chen X., Yan S., Wang H., Lu Z., Xia X., Liang M., Wu Y. L., Zheng L., Cao Q., Ding Z., RSC Adv., 2016, 6(30), 25416CrossRefGoogle Scholar
  50. [50]
    Peng L., Zhou Z., Wei R., Li K., Song P., Tong A., Dyes. Pigments, 2014, 108, 24CrossRefGoogle Scholar
  51. [51]
    Peng L., Gao M., Cai X., Zhang R., Li K., Feng G., Tong A., Liu B., J. Mater. Chem. B, 2015, 3(47), 9168CrossRefGoogle Scholar
  52. [52]
    Gao M., Sim C. K., Leung C. W. T., Hu Q., Feng G., Xu F., Tang B. Z., Liu B., Chem. Commun., 2014, 50(61), 8312CrossRefGoogle Scholar
  53. [53]
    Liu L., Wu B., Yu P., Zhuo R. X., Huang S. W., Polym. Chem., 2015, 6(29), 5185CrossRefGoogle Scholar
  54. [54]
    Hu Q., Gao M., Feng G., Liu B., Angew. Chem. Int. Edit., 2014, 53(51), 14225CrossRefGoogle Scholar
  55. [55]
    Gao M., Hu Q., Feng G., Tomczak N., Liu R., Xing B., Tang B. Z., Liu B., Adv. Healthc. Mater., 2015, 4(5), 659CrossRefPubMedGoogle Scholar
  56. [56]
    Huang J., Zhu H., Liang H., Lu J., Polym. Chem., 2016, 7(29), 4761CrossRefGoogle Scholar
  57. [57]
    Jim C. K. W., Qin A., Lam J. W. Y., Häussler M., Liu J., Yuen M. M. F., Kim J. K., Ng K. M., Tang B. Z., Macromolecules, 2009, 42(12), 4099CrossRefGoogle Scholar
  58. [58]
    Lu H. L., Syu W. J., Nishiyama N., Kataoka K., Lai P. S., J. Control Release, 2011, 155(3), 458CrossRefPubMedGoogle Scholar

Copyright information

© Jilin University, The Editorial Department of Chemical Research in Chinese Universities and Springer-Verlag GmbH 2019

Authors and Affiliations

  1. 1.Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchunP. R. China
  2. 2.University of Chinese Academy of SciencesBeijingP. R. China
  3. 3.Jilin Biomedical Polymers Engineering Laboratory, Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchunP. R. China

Personalised recommendations