Enzyme-assisted Photoinitiated Polymerization-induced Self-assembly in Continuous Flow Reactors with Oxygen Tolerance

Abstract

Polymerization-induced self-assembly (PISA) is an emerging method for the preparation of block copolymer nano-objects at high concentrations. However, most PISA formulations have oxygen inhibition problems and inert atmospheres (e.g. argon, nitrogen) are usually required. Moreover, the large-scale preparation of block copolymer nano-objects at room temperature is challenging. Herein, we report an enzyme-assisted photoinitiated polymerization-induced self-assembly (photo-PISA) in continuous flow reactors with oxygen tolerance. The addition of glucose oxidase (GOx) and glucose into the reaction mixture can consume oxygen efficiently and constantly, allow the flow photo-PISA to be performed under open-air conditions. Polymerization kinetics indicated that only a small amount of GOx (0.5 μmol/L) was needed to achieve the oxygen tolerance. Block copolymer nano-objects with different morphologies can be prepared by varying reaction conditions including the degree of polymerization (DP) of core-forming block, monomer concentration, reaction temperature, and solvent composition. We expect this study will provide a facile platform for the large-scale production of block copolymer nano-objects with different morphologies at room temperature.

This is a preview of subscription content, access via your institution.

References

  1. 1

    Zhu, Y.; Yang, B.; Chen, S.; Du, J. Polymer vesicles: mechanism, preparation, application, and responsive behavior. Prog. Polym. Sci. 2017, 64, 1–22.

    CAS  Article  Google Scholar 

  2. 2

    Zhang, W. J.; Hong, C. Y.; Pan, C. Y. Polymerization-induced self-assembly of functionalized block copolymer nanoparticles and their application in drug delivery. Macromol. Rapid Commun. 2019, 40, 1800279.

    Article  CAS  Google Scholar 

  3. 3

    He, J.; Cao, J.; Chen, Y.; Zhang, L.; Tan, J. Thermoresponsive block copolymer vesicles by visible light-initiated seeded polymerization-induced self-assembly for temperature-regulated enzymatic nanoreactors. ACS Macro Lett. 2020, 9, 533–539.

    CAS  Article  Google Scholar 

  4. 4

    Jin, X. H.; Price, M. B.; Finnegan, J. R.; Boott, C. E.; Richter, J. M.; Rao, A.; Menke, S. M.; Friend, R. H.; Whittell, G. R.; Manners, I. Long-range exciton transport in conjugated polymer nanofibers prepared by seeded growth. Science 2018, 360, 897–900.

    CAS  PubMed  Article  Google Scholar 

  5. 5

    Ning, Y.; Fielding, L. A.; Ratcliffe, L. P. D.; Wang, Y. W.; Meldrum, F. C.; Armes, S. P. Occlusion of sulfate-based diblock copolymer nanoparticles within calcite: effect of varying the surface density of anionic stabilizer chains. J. Am. Chem. Soc. 2016, 138, 11734–11742.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  6. 6

    Nguyen, D.; Such, C.; Hawkett, B. Polyreer-TiO2 oomosssite nanorattles via RAFT-mediated emulsion polymerization. J. Polym. Sci., Part A: Polym. Chem. 2012, 50, 346–352.

    CAS  Article  Google Scholar 

  7. 7

    He, J.; Xu, Q.; Tan, J.; Zhang, L. Ketone-functionalized polymer nano-objects prepared via photoinitiated polymerization-induced self-assembly (photo-PISA) using a poly(diacetone acrylamide)-based macro-RAFT agent. Macromol. Rapid Commun. 2019, 40, 1800296.

    Article  CAS  Google Scholar 

  8. 8

    Tian, H.; Qin, J.; Hou, D.; Li, Q.; Li, C.; Wu, Z. S.; Mai, Y. General interfacial self-assembly engineering for patterning two-dimensional polymers with cylindrical mesopores on graphene. Angew. Chem. Int. Ed. 2019, 58, 10173–10178.

    CAS  Article  Google Scholar 

  9. 9

    Mai, Y.; Eisenberg, A. Self-assembly of block copolymers. Chem. Soc. Rev. 2012, 41, 5969–5985.

    CAS  PubMed  Article  Google Scholar 

  10. 10

    Wan, W. M.; Hong, C. Y.; Pan, C. Y. One-pot synthesis of nanomaterials via RAFT polymerization induced self-assembly and morphology transition. Chem. Commun. 2009, 5883–5885.

    Google Scholar 

  11. 11

    Wan, W. M.; Pan, C. Y. One-pot synthesis of polymeric nanomaterials via RAFT dispersion polymerization induced self-assembly and re-organization. Polym. Chem. 2010, 1, 1475–1484.

    CAS  Article  Google Scholar 

  12. 12

    He, W. D.; Sun, X. L.; Wan, W. M.; Pan, C. Y. Multiple morphologies of PAA-b-PSt assemblies throughout RAFT dispersion polymerization of styrene with PAA macro-CTA. Macromolecules 2011, 44, 3358–3365.

    CAS  Article  Google Scholar 

  13. 13

    Boissé, S.; Rieger, J.; Belal, K.; Di-Cicco, A.; Beaunier, P.; Li, M. H.; Charleux, B. Amphiphilic block copolymer nano-fibers via RAFT-mediated polymerization in aqueous dispersed system. Chem. Commun. 2010, 46, 1950–1952.

    Article  CAS  Google Scholar 

  14. 14

    Charleux, B.; Delaittre, G.; Rieger, J.; D’Agosto, F. Polymerization-induced self-assembly: from soluble macromolecules to block copolymer nano-objects in one step. Macromolecules 2012, 45, 6753–6765.

    CAS  Article  Google Scholar 

  15. 15

    Li, Y.; Armes, S. P. RAFT synthesis of sterically stabilized methacrylic nanolatexes and vesicles by aqueous dispersion polymerization. Angew. Chem. Int. Ed. 2010, 49, 4042–4046.

    CAS  Article  Google Scholar 

  16. 16

    Blanazs, A.; Madsen, J.; Battaglia, G.; Ryan, A. J.; Armes, S. P. Mechanistic insights for block copolymer morphologies: how do worms form vesicles? J. Am. Chem. Soc. 2011, 133, 16581–16587.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  17. 17

    Ding, Z.; Ding, M.; Gao, C.; Boyer, C.; Zhang, W. In situ synthesis of coil-coil diblock copolymer nanotubes and tubular Ag/polymer nanocomposites by RAFT dispersion polymerization in poly(ethylene glycol). Macromolecules 2017, 50, 7593–7602.

    CAS  Article  Google Scholar 

  18. 18

    Huang, J.; Guo, Y.; Gu, S.; Han, G.; Duan, W.; Gao, C.; Zhang, W. Multicompartment block copolymer nanoparticles: recent advances and future perspectives. Polym. Chem. 2019, 10, 3426–3435.

    CAS  Article  Google Scholar 

  19. 19

    Li, S.; Nie, H.; Gu, S.; Han, Z.; Han, G.; Zhang, W. Synthesis of multicompartment nanoparticles of ABC miktoarm star polymers by seeded RAFT dispersion polymerization. ACS Macro Lett. 2019, 8, 783–788.

    Article  CAS  Google Scholar 

  20. 20

    Li, S.; Han, G.; Zhang, W. Cross-linking approaches for block copolymer nano-assemblies via RAFT-mediated polymerization-induced self-assembly. Polym. Chem. 2020, 11, 4681–4692.

    CAS  Article  Google Scholar 

  21. 21

    Wang, X.; Shen, L.; An, Z. Dispersion polymerization in environmentally benign solvents via reversible deactivation radical polymerization. Prog. Polym. Sci. 2018, 83, 1–27.

    Article  CAS  Google Scholar 

  22. 22

    Wang, X.; Man, S.; Zheng, J.; An, Z. Alkyl a-hydroxymethyl acrylate monomers for aqueous dispersion polymerization-induced self-assembly. ACS Macro Lett. 2018, 7, 1461–1467.

    CAS  Article  Google Scholar 

  23. 23

    Lv, F.; An, Z.; Wu, P. What determines the formation of block copolymer nanotubes? Macromolecules 2020, 53, 367–373.

    CAS  Article  Google Scholar 

  24. 24

    Chen, X.; Liu, L.; Huo, M.; Zeng, M.; Peng, L.; Feng, A.; Wang, X.; Yuan, J. Direct synthesis of polymer nanotubes by aqueous dispersion polymerization of a cyclodextrin/styrene complex. Angew. Chem. Int. Ed. 2017, 56, 16541–16545.

    CAS  Article  Google Scholar 

  25. 25

    Huo, M.; Zeng, M.; Wu, D.; Wei, Y.; Yuan, J. Topoolggiaal engineering of amphiphilic copolymers via RAFT dispersion copolymerization of benzyl methacrylate and 2-(perfluorooctyl)ethyl methacrylate for polymeric assemblies with tunable nanostructures. Polym. Chem. 2018, 9, 912–919.

    CAS  Article  Google Scholar 

  26. 26

    Huo, M.; Ye, Q.; Che, H.; Wang, X.; Wei, Y.; Yuan, J. Polymer assemblies with nanostructure-correlated aggregation-induced emission. Macromolecules 2017, 50, 1126–1133.

    CAS  Article  Google Scholar 

  27. 27

    Zeng, R.; Chen, Y.; Zhang, L.; Tan, J. R-RAFT or Z-RAFT? Well-defined star block copolymer nano-objects prepared by RAFT-mediated polymerization-induced self-assembly. Macromolecules 2020, 53, 1557–1566.

    CAS  Article  Google Scholar 

  28. 28

    Tan, J.; Sun, H.; Yu, M.; Sumerlin, B. S.; Zhang, L. Photo-PISA: shedding light on polymerization-induced self-assembly. ACS Macro Lett. 2015, 4, 1249–1253.

    CAS  Article  Google Scholar 

  29. 29

    Dai, X.; Zhang, Y.; Yu, L.; Li, X.; Zhang, L.; Tan, J. Seedded photoinitiated polymerization-induced self-assembly: cylindrical micelles with patchy structures prepared via the chain extension of a third block. ACS Macro Lett. 2019, 8, 955–961.

    CAS  Article  Google Scholar 

  30. 30

    Liu, D.; He, J.; Zhang, L.; Tan, J. 100th Anniversary of macromolecular science viewpoint: heterogenous reversible deactivation radical polymerization at room temperature. Recent advances and future opportunities. ACS Macro Lett. 2019, 8, 1660–1669.

    CAS  Article  Google Scholar 

  31. 31

    Zhang, Y.; Yu, L.; Dai, X.; Zhang, L.; Tan, J. Structural difference in macro-RAFT agents redirects polymerization-induced self-assembly. ACS Macro Lett. 2019, 8, 1102–1109.

    CAS  Article  Google Scholar 

  32. 32

    Yu, L.; Dai, X.; Zhang, Y.; Zeng, Z.; Zhang, L.; Tan, J. Better RAFT control is better? Insights into the preparation of monodisperse surface-functional polymeric microspheres by photoinitiated RAFT dispersion polymerization Macromolecules 2019, 52, 7267–7277.

    CAS  Article  Google Scholar 

  33. 33

    Yu, L.; Zhang, Y.; Dai, X.; Xu, Q.; Zhang, L.; Tan, J. Open-air preparation of cross-linked CO2-responsive polymer vesicles by enzyme-assisted photoinitiated polymerization-induced self-assembly. Chem. Commun. 2019, 55, 11920–11923.

    CAS  Article  Google Scholar 

  34. 34

    Liu, D.; Cai, W.; Zhang, L.; Boyer, C.; Tan, J. Efficient photoinitiated polymerization-induced self-assembly with oxygen tolerance through dual-wavelength type I photoinitiation and photoinduced deoxygenation. Macromolecules 2020, 53, 1212–1223.

    CAS  Article  Google Scholar 

  35. 35

    Zeng, R.; Chen, Y.; Zhang, L.; Tan, J. Uncontrolled polymerization that occurred during photoinitiated RAFT dispersion polymerization of acrylic monomers promotes the formation of uniform raspberry-like polymer particles. Polym. Chem. 2020, 11, 4591–4603.

    CAS  Article  Google Scholar 

  36. 36

    Jiang, Y.; Xu, N.; Han, J.; Yu, Q.; Guo, L.; Gao, P.; Lu, X.; Cai, Y. The direct synthesis of interface-decorated reactive block copolymer nanoparticles via polymerisation-induced self-assembly. Polym. Chem. 2015, 6, 4955–4965.

    CAS  Article  Google Scholar 

  37. 37

    Yu, Q.; Ding, Y.; Cao, H.; Lu, X.; Cai, Y. Use of polyion complexation for polymerization-induced self-assembly in water under visible light irradiation at 25 °C. ACS Macro Lett. 2015, 4, 1293–1296.

    CAS  Article  Google Scholar 

  38. 38

    Huang, L.; Ding, Y.; Ma, Y.; Wang, L.; Liu, Q.; Lu, X.; Cai, Y. Colloidal stable PIC vesicles and lamellae enabled by wavelength-orthogonal disulfide exchange and polymerization-induced electrostatic self-assembly. Macromolecules 2019, 52, 4703–4712.

    CAS  Article  Google Scholar 

  39. 39

    Ding, Y.; Cai, M.; Cui, Z.; Huang, L.; Wang, L.; Lu, X.; Cai, Y. Synthesis of low-dimensional polyion complex nanomaterials via polymerization-induced electrostatic self-assembly. Angew. Chem. Int. Ed. 2018, 57, 1053–1056.

    CAS  Article  Google Scholar 

  40. 40

    Gao, P.; Cao, H.; Ding, Y.; Cai, M.; Cui, Z.; Lu, X.; Cai, Y. Synthesis of hydrogen-bonded pore-switchable cylindrical vesicles via visible-light-mediated RAFT room-temperature aqueous dispersion polymerization. ACS Macro Lett. 2016, 5, 1327–1331.

    CAS  Article  Google Scholar 

  41. 41

    Varlas, S.; Foster, J. C.; Georgiou, P. G.; Keogh, R.; Husband, J. T.; Williams, D. S.; O’Reilly, R. K. Tuning the membrane permeability of polymersome nanoreactors developed by aqueous emulsion polymerization-induced self-assembly. Nanoscale 2019, 11, 12643–12654.

    CAS  PubMed  Article  Google Scholar 

  42. 42

    Blackman, L. D.; Doncom, K. E. B.; Gibson, M. I.; O’Reilly, R. K. Comparison of photo- and thermally initiated polymerization-induced self-assembly: a lack of end group fidelity drives the formation of higher order morphologies. Polym. Chem. 2017, 8, 2860–2871.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  43. 43

    Xu, S.; Ng, G.; Xu, J.; Kuchel, R. P.; Yeow, J.; Boyer, C. 2-(Methylthio)ethyl methacrylate: a versatile monomer for stimuli responsiveness and polymerization-induced self-assembly in the presence of air. ACS Macro Lett. 2017, 6, 1237–1244.

    CAS  Article  Google Scholar 

  44. 44

    Yeow, J.; Boyer, C. Photoinitiated polymerization-induced self-assembly (photo-PISA): new insights and opportunities. Adv. Sci. 2017, 4, 1700137.

    Article  CAS  Google Scholar 

  45. 45

    Yeow, J.; Shanmugam, S.; Corrigan, N.; Kuchel, R. P.; Xu, J.; Boyer, C. A polymerization-induced self-assembly approach to nanoparticles loaded with singlet oxygen generators. Macromolecules 2016, 49, 7277–7285.

    CAS  Article  Google Scholar 

  46. 46

    Tan, J.; Liu, D.; Huang, C.; Li, X.; He, J.; Xu, Q.; Zhang, L. Photoinitiated polymerization-induced self-assembly of glycidyl methacrylate for the synthesis of epoxy-functionalized block copolymer nano-objects. Macromol. Rapid Commun. 2017, 38, 1700195.

    Article  CAS  Google Scholar 

  47. 47

    Xu, Q.; Zhang, Y.; Li, X.; He, J.; Tan, J.; Zhang, L. Enzyme catalysis-induced RAFT polymerization in water for the preparation of epoxy-functionalized triblock copolymer vesicles. Polym. Chem. 2018, 9, 4908–4916.

    CAS  Article  Google Scholar 

  48. 48

    Tan, J.; Bai, Y.; Zhang, X.; Huang, C.; Liu, D.; Zhang, L. Low-temperature synthesis of thermoresponsive diblock copolymer nano-objects via aqueous photoinitiated polymerization-induced self-assembly (photo-PISA) using thermoresponsive Macro-RAFT agents. Macromol. Rapid Commun. 2016, 37, 1434–1440.

    CAS  PubMed  Article  Google Scholar 

  49. 49

    Wang, L.; Ding, Y.; Liu, Q.; Zhao, Q.; Dai, X.; Lu, X.; Cai, Y. Sequence-controlled polymerization-induced self-assembly. ACS Macro Lett. 2019, 8, 623–628.

    CAS  Article  Google Scholar 

  50. 50

    Zhang, Y.; He, J.; Dai, X.; Yu, L.; Tan, J.; Zhang, L. Combining the power of heat and light: temperature-programmed photoinitiated RAFT dispersion polymerization to tune polymerization-induced self-assembly. Polym. Chem. 2019, 10, 3902–3911.

    CAS  Article  Google Scholar 

  51. 51

    Ma, Y.; Gao, P.; Ding, Y.; Huang, L.; Wang, L.; Lu, X.; Cai, Y. Visible light initiated thermoresponsive aqueous dispersion polymerization-induced self-assembly. Macromolecules 2019, 52, 1033–1041.

    Article  CAS  Google Scholar 

  52. 52

    Zhao, Q.; Liu, Q.; Li, C.; Cao, L.; Ma, L.; Wang, X.; Cai, Y. Noncovalent structural locking of thermoresponsive polyion complex micelles, nanowires, and vesicles via polymerization-induced electrostatic self-assembly using an arginine-like monomer. Chem. Commun. 2020, 56, 4954–4957.

    CAS  Article  Google Scholar 

  53. 53

    Tan, J.; Li, X.; Zeng, R.; Liu, D.; Xu, Q.; He, J.; Zhang, Y.; Dai, X.; Yu, L.; Zeng, Z.; Zhang, L. Expanding the scope of polymerization-induced self-assembly: Z-RAFT-mediated photoinitiated dispersion polymerization. ACS Macro Lett. 2018, 7, 255–262.

    CAS  Article  Google Scholar 

  54. 54

    Zhou, Y.; Gu, Y.; Jiang, K.; Chen, M. Droplet-flow photopolymerization aided by computer: overcoming the challenges of viscosity and facilitating the generation of copolymer libraries. Macromolecules 2019, 52, 5611–5617.

    CAS  Article  Google Scholar 

  55. 55

    Reis, M. H.; Leibfarth, F. A.; Pitet, L. M. Polymerizations in continuous flow: recent advances in the synthesis of diverse polymeric materials. ACS Macro Lett. 2020, 9, 123–133.

    CAS  Article  Google Scholar 

  56. 56

    Zaquen, N.; Rubens, M.; Corrigan, N.; Xu, J.; Zetterlund, P. B.; Boyer, C.; Junkers, T. Polymer synthesis in continuous flow reactors. Prog. Polym. Sci. 2020, 107, 101256.

    CAS  Article  Google Scholar 

  57. 57

    Zaquen, N.; Azizi, W. A. A. W.; Yeow, J.; Kuchel, R. P.; Junkers, T.; Zetterlund, P. B.; Boyer, C. Alcohol-based PISA in batch and flow: exploring the role of photoinitiators. Polym. Chem. 2019, 10, 2406–2414.

    CAS  Article  Google Scholar 

  58. 58

    Zaquen, N.; Yeow, J.; Junkers, T.; Boyer, C.; Zetterlund, P. B. Visible light-mediated polymerization-induced self-assembly using continuous flow reactors. Macromolecules 2018, 51, 5165–5172.

    CAS  Article  Google Scholar 

  59. 59

    Tan, J.; Liu, D.; Bai, Y.; Huang, C.; Li, X.; He, J.; Xu, Q.; Zhang, L. Enzyme-assisted photoinitiated polymerization-induced self-assembly: an oxygen-tolerant method for preparing block copolymer nano-objects in open vessels and multiwell plates. Macromolecules 2017, 50, 5798–5806.

    CAS  Article  Google Scholar 

  60. 60

    Tan, J.; Liu, D.; Bai, Y.; Huang, C.; Li, X.; He, J.; Xu, Q.; Zhang, X.; Zhang, L. An insight into aqueous photoinitiated polymerization-induced self-assembly (photo-PISA) for the preparation of diblock copolymer nano-objects. Polym. Chem. 2017, 8, 1315–1327.

    CAS  Article  Google Scholar 

  61. 61

    Blanazs, A.; Ryan, A. J.; Armes, S. P. Predictive phase diagrams for RAFT aqueous dispersion polymerization: effect of block copolymer composition, molecular weight, and copolymer concentration. Macromolecules 2012, 45, 5099–5107.

    CAS  Article  Google Scholar 

  62. 62

    Tan, J.; He, J.; Li, X.; Xu, Q.; Huang, C.; Liu, D.; Zhang, L. Rapid synthesis of well-defined all-acrylic diblock copolymer nano-objects via alcoholic photoinitiated polymerization-induced self-assembly (photo-PISA). Polym. Chem. 2017, 8, 6853–6864.

    CAS  Article  Google Scholar 

  63. 63

    Zhang, Y.; Han, G.; Cao, M.; Guo, T.; Zhang, W. Influence of solvophilic homopolymers on RAFT polymerization-induced self-assembly. Macromolecules 2018, 51, 4397–4406.

    CAS  Article  Google Scholar 

Download references

Acknowledgments

This work was financially supported by the National Natural Science Foundation of China (Nos. 21971047 and 21504017) and Innovation Project of Education Department in Guangdong (No. 2018KTSCX053). Y.C. acknowledges the support from Guangdong Special Support Program (No. 2017TX04N371). J.T. acknowledges the support from Pearl River Young Scholar of Guangdong.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Jian-Bo Tan.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Cai, WB., Liu, DD., Chen, Y. et al. Enzyme-assisted Photoinitiated Polymerization-induced Self-assembly in Continuous Flow Reactors with Oxygen Tolerance. Chin J Polym Sci (2021). https://doi.org/10.1007/s10118-021-2533-z

Download citation

Keywords

  • Polymerization-induced self-assembly
  • Reversible addition-fragmentation chain transfer (RAFT) polymerization
  • Photoinitiation
  • Oxygen tolerance