Synthetic chemists have devoted tremendous effort towards the production of precision synthetic polymers with defined sequences and specific functions. However, the creation of a general technology that enables precise control over monomer sequence, with efficient isolation of the target polymers, is highly challenging. Here, we report a robust strategy for the production of sequence-defined synthetic polymers through a combination of liquid-phase synthesis and selective molecular sieving. The polymer is assembled in solution with real-time monitoring to ensure couplings proceed to completion, on a three-armed star-shaped macromolecule to maximize efficiency during the molecular sieving process. This approach is applied to the construction of sequence-defined polyethers, with side-arms at precisely defined locations that can undergo site-selective modification after polymerization. Using this versatile strategy, we have introduced structural and functional diversity into sequence-defined polyethers, unlocking their potential for real-life applications in nanotechnology, healthcare and information storage.

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Change history

  • 08 January 2019

    In the version of this Article originally published, the authors inadvertently cited ref. 10 in two places in the first paragraph. They would like to clarify that it should not have been cited in the sentence that starts “Polymer chemists have employed strategies such as single monomer insertion...” as it mistakenly implied that the IEG+ method described in ref. 10 could not produce unimolecular polymers; it can do so, as was demonstrated in ref. 10. The authors would also like to clarify that ref. 10 should not have been cited in the sentence that starts “Moreover, solid-phase synthesis is generally difficult to scale up...", as it implied that ref. 10 uses solid-phase synthesis; it does not, and is a purely liquid-phase process. The citation of ref. 10 has now been removed from these two sentences, but has been included elsewhere in the first two paragraphs of the Article as follows. In the first paragraph, at the end of the sentence “In iterative synthesis, specific monomers are added one at a time, or as multiples, to the end of a growing polymer chain, then reaction debris is separated from the chain extended polymer, and the cycle is repeated using the next monomer in the sequence10–12.”; this sentence has been further amended to indicate multiple monomers can also be added. The reference has also been added to the end of the first sentence of the second paragraph, which starts “Consequently, liquid-phase iterative synthetic methods...”, and in the third sentence of that paragraph, which now starts “For example, Johnson10, Whiting....”.


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This work was supported financially by the Engineering and Physical Sciences Research Council (EPSRC, EP/M003949/1) and GlaxoSmithKline. The authors acknowledge the EPSRC UK National Mass Spectrometry Facility at Swansea University for MALDI–TOF–MS measurements. The authors thank R. T. Woodward for GPC analysis and C. Yu for molecular modelling. The authors thank Huntsman for provision of Jeffamines.

Author information


  1. Department of Chemical Engineering, Imperial College London, London, UK

    • Ruijiao Dong
    • , Ruiyi Liu
    • , Piers R. J. Gaffney
    • , Marc Schaepertoens
    • , Patrizia Marchetti
    • , Rongjun Chen
    •  & Andrew G. Livingston
  2. EPSRC UK National Mass Spectrometry Facility (NMSF), Swansea University Medical School, Swansea, UK

    • Christopher M. Williams


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R.D., P.R.J.G., R.C. and A.G.L. conceived the project. R.D., P.R.J.G. and A.G.L. designed the experiments. R.D. carried out the synthesis and characterization of BnO-BB, N3-BB, PmbS-BB and polymers, and analysed the data. R.L. synthesized octyl-BB. R.D. conducted the DSC, TGA, UV–vis and fluorescence spectrometry measurements. R.D. and R.L. carried out organic solvent nanofiltration. R.L. performed liquid–liquid porometry and membrane screening. M.S. provided the hub molecule. P.M. prepared the PBI membranes. C.M.W. performed the MS/MS measurements. R.D. and P.R.J.G. wrote the manuscript. A.G.L. guided the project. All authors discussed the results and edited the manuscript.

Competing interests

Imperial Innovations has filed a UK patent application (no. 1516067.4) related to defined monomer sequence polymers (leading to PCT/GB2016/052801). A.G.L., P.R.J.G., R.D., R.C., P.M. and R.L. are listed as inventors. All other authors declare no competing interests.

Corresponding author

Correspondence to Andrew G. Livingston.

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    Supplementary experimental methods, synthetic procedures and compound characterization

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