Article | Published:

Iterative exponential growth of stereo- and sequence-controlled polymers

Nature Chemistry volume 7, pages 810815 (2015) | Download Citation

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.

  • Compound C6H8O2

    (R)-2-((prop-2-yn-1-yloxy)methyl)oxirane

  • Compound C6H8O2

    (S)-2-((prop-2-yn-1-yloxy)methyl)oxirane

  • Compound C12H22O2Si

    (R)-tert-butyldimethyl(3-(oxiran-2-ylmethoxy)prop-1-yn-1-yl)silane

  • Compound C12H22O2Si

    (S)-tert-butyldimethyl(3-(oxiran-2-ylmethoxy)prop-1-yn-1-yl)silane

  • Compound C20H33N3O5Si

    (S,R)-G1-OAc

  • Compound C20H33N3O5Si

    2(R)-G1-OAc

  • Compound C25H37N3O4Si

    2(R)-G1-OBn

  • Compound C36H55N9O11Si

    2(S,R)-G2-(OAc)3

  • Compound C36H55N9O11Si

    4(R)-G2-(OAc)3

  • Compound C46H63N9O9Si

    4(R)-G2-(OBn-OAc)-OBn

  • Compound C68H99N21O23Si

    4(S,R)-G3-(OAc)7

  • Compound C68H99N21O23Si

    8(R)-G3-(OAc)7

  • Compound C88H115N21O19Si

    8(R)-G3-(OBn-OAc)3-OBn

  • Compound C132H187N45O47Si

    8(S,R)-G4-(OAc)15

  • Compound C132H187N45O47Si

    16(R)-G4-(OAc)15

  • Compound C172H219N45O39Si

    16(R)-G4-(OBn-OAc)7-OBn

  • Compound C152H203N45O43Si

    16(R)-G4-(OAc)8-(OBn-OAc)3-OBn

  • Compound C260H363N93O95Si

    16(S,R)-G5-(OAc)31

  • Compound C300H395N93O87Si

    8(S,R)-(OAc)15-G5-16(R)-(OAc-OBn)8

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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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Affiliations

  1. Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA

    • Jonathan C. Barnes
    • , Deborah J. C. Ehrlich
    • , Angela X. Gao
    • , Frank A. Leibfarth
    • , Yivan Jiang
    • , Erica Zhou
    • , Timothy F. Jamison
    •  & Jeremiah A. Johnson

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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.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Jeremiah A. Johnson.

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DOI

https://doi.org/10.1038/nchem.2346

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