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Tailored silyl ether monomers enable backbone-degradable polynorbornene-based linear, bottlebrush and star copolymers through ROMP

Abstract

Ring-opening metathesis polymerization of norbornene-based (macro)monomers is a powerful approach for the synthesis of macromolecules with diverse compositions and complex architectures. Nevertheless, a fundamental limitation of polymers prepared by this strategy is their lack of facile degradability, limiting their utility in a range of applications. Here we describe a class of readily available bifunctional silyl ether-based cyclic olefins that copolymerize efficiently with norbornene-based (macro)monomers to provide copolymers with backbone degradability under mildly acidic aqueous conditions and degradation rates that can be tuned over several orders of magnitude, depending on the silyl ether substituents. These monomers can be used to manipulate the in vivo biodistribution and clearance rate of polyethylene glycol-based bottlebrush polymers, as well as to synthesize linear, bottlebrush and brush-arm star copolymers with degradable segments. We expect that this work will enable preparation of degradable polymers by ROMP for biomedical applications, responsive self-assembly and improved sustainability.

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Fig. 1: The study design and initial results.
Fig. 2: Norbornene monomer scope.
Fig. 3: Bifunctional silyl ether monomer scope.
Fig. 4: Bottlebrush copolymer degradation studies as a function of time, pH and bifunctional silyl ether composition.
Fig. 5: Regioselective degradation of bifunctional silyl ether-containing BASPs.
Fig. 6: Biological studies of fluorescently labelled bottlebrush (co)polymers.

Data availability

All data that support the findings of this study are available within the Article and its Supplementary Information, and/or from the corresponding author on reasonable request.

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Acknowledgements

The authors thank the National Institutes of Health (grant no. 1R01CA220468-01) for supporting this work. P.S. was supported by a fellowship from the American Cancer Society. H.V.-T.N was supported by the National Science Foundation (Graduate Research Fellowship).

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P.S. and J.A.J. conceived the idea. P.S. conducted all synthesis and characterization studies. P.S. and H.V.-T.N. conducted cell culture and in vivo studies. P.S. and J.A.J. wrote the manuscript. All authors discussed the results and commented on the manuscript.

Corresponding author

Correspondence to Jeremiah A. Johnson.

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Competing interests

P.S. and J.A.J. are named inventors on a patent application (US Patent application no. 16/542824) filed by the Massachusetts Institute of Technology on the monomers and copolymers described in this work.

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Supplementary information

Supplementary Information

Procedures for the synthesis and characterization of the materials described in the main text, procedures for all in vitro and in vivo biological experiments, and Supplementary Scheme 1, Table 1 and Figs. 1–40

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Shieh, P., Nguyen, H.VT. & Johnson, J.A. Tailored silyl ether monomers enable backbone-degradable polynorbornene-based linear, bottlebrush and star copolymers through ROMP. Nat. Chem. 11, 1124–1132 (2019). https://doi.org/10.1038/s41557-019-0352-4

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