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Iterative exponential growth of stereo- and sequence-controlled polymers

Abstract

Chemists have long sought sequence-controlled synthetic polymers that mimic nature's biopolymers, but a practical synthetic route that enables absolute control over polymer sequence and structure remains a key challenge. Here, we report an iterative exponential growth plus side-chain functionalization (IEG+) strategy that begins with enantiopure epoxides and facilitates the efficient synthesis of a family of uniform >3 kDa macromolecules of varying sequence and stereoconfiguration that are coupled to produce unimolecular polymers (>6 kDa) with sequences and structures that cannot be obtained using traditional polymerization techniques. Selective side-chain deprotection of three hexadecamers is also demonstrated, which imbues each compound with the ability to dissolve in water. We anticipate that these new macromolecules and the general IEG+ strategy will find broad application as a versatile platform for the scalable synthesis of sequence-controlled polymers.

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Figure 1: Traditional solid/solution-phase syntheses versus IEG+.
Figure 2: 1H NMR characterization.
Figure 3: MALDI mass spectra and GPC traces.
Figure 4: Syntheses of isotactic hexadecamers.
Figure 5: MALDI mass spectra and GPC traces of the isotactic, alternating sequence IEG+ oligotriazoles.
Figure 6: A 32-unit polymer consisting of a complex sequence and selective deprotection of three hexadecamers.

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Acknowledgements

The authors acknowledge DuPont for support of this work. J.C.B. acknowledges the Howard Hughes Medical Institute (Postdoctoral Fellow of the Life Sciences Research Foundation), and F.A.L. acknowledges the National Science Foundation (Postdoctoral Sustainability Fellowship).

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Contributions

J.A.J. conceived of the IEG+ concept. J.A.J. and J.C.B. conceived the molecular designs and synthetic protocols. J.C.B., D.J.C.E., A.X.G., Y.J. and E.Z. carried out the syntheses. J.C.B. characterized each compound by NMR, GPC and MALDI, and J.C.B. and J.A.J. analysed the data. F.A.L. performed DSC/TGA experiments. J.C.B. and J.A.J. wrote the paper. J.C.B., D.J.C.E., A.X.G., F.A.L., Y.J., E.Z., T.F.J. and J.A.J. discussed the results and edited the manuscript.

Corresponding author

Correspondence to Jeremiah A. Johnson.

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Barnes, J., Ehrlich, D., Gao, A. et al. Iterative exponential growth of stereo- and sequence-controlled polymers. Nature Chem 7, 810–815 (2015). https://doi.org/10.1038/nchem.2346

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