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SuFExable polymers with helical structures derived from thionyl tetrafluoride


Sulfur(vi) fluoride exchange (SuFEx) is a category of click chemistry that enables covalent linking of modular units through sulfur(vi) connective hubs. The efficiency of SuFEx and the stability of the resulting bonds have led to polymer chemistry applications. Now, we report the SuFEx click chemistry synthesis of several structurally diverse SOF4-derived copolymers based on the polymerization of bis(iminosulfur oxydifluorides) and bis(aryl silyl ethers). This polymer class presents two key characteristics. First, the [–N=S(=O)F–O–] polymer backbone linkages are themselves SuFExable and undergo precise SuFEx-based post-modification with phenols or amines to yield branched functional polymers. Second, studies of individual polymer chains of several of these new materials indicate helical polymer structures. The robust nature of SuFEx click chemistry offers the potential for post-polymerization modification, enabling the synthesis of materials with control over composition and conformation.

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Fig. 1: SuFEx click chemistry for polymer synthesis.
Fig. 2: Kinetic profile of the polymerization of 1-1 (1 mmol) and 2-1 (1 mmol) (0.5 M in NMP, 3 mol% DBU).
Fig. 3: Post-polymerization modification of polymer 3-1 using sequential SuFEx and CuAAC click chemistry.
Fig. 4: The multidimensional connectivity of the S(vi) hubs: detailed structure studies.
Fig. 5: Substitution of S–F bond of optically pure sulfurofluoridoimidate in the presence of BEMP, racemization experiment for sulfurofluoridoimidate in the presence of DBU and reactive selectivity of iminosulfur oxydifluoride with aryl silyl ether.

Data availability

Data supporting the findings of this study are available within the Article and its Supplementary Information. Crystallographic data for the structures reported in this Article have been deposited at the Cambridge Crystallographic Data Centre, under deposition no. CCDC 2026570 [(R)-(−)-16]. Copies of the data can be obtained free of charge via Source data are provided with this paper.


  1. 1.

    Sharpless, K. B. & Kolb, H. C. in Book of Abstracts, 217th ACS National Meeting, Anaheim, CA, March 21–25 145538 (ACS, 1999).

  2. 2.

    Kolb, H. C., Finn, M. G. & Sharpless, K. B. Click chemistry: diverse chemical function from a few good reactions. Angew. Chem. Int. Ed. 40, 2004–2021 (2001).

    CAS  Article  Google Scholar 

  3. 3.

    Tornoe, C. W., Christensen, C. & Meldal, M. Peptidotriazoles on solid phase: 1,2,3-triazoles by regiospecific copper(i)-catalyzed 1,3-dipolar cycloadditions of terminal alkynes to azides. J. Org. Chem. 67, 3057–3064 (2002).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  4. 4.

    Rostovtsev, V. V., Green, L. G., Fokin, V. V. & Sharpless, K. B. A stepwise Huisgen cycloaddition process: copper(i)-catalyzed regioselective ‘ligation’ of azides and terminal alkynes. Angew. Chem. Int. Ed. 41, 2596–2599 (2002).

    CAS  Article  Google Scholar 

  5. 5.

    Dong, J., Krasnova, L., Finn, M. G. & Sharpless, K. B. Sulfur(vi) fluoride exchange (SuFEx): another good reaction for click chemistry. Angew. Chem. Int. Ed. 53, 9430–9448 (2014).

    CAS  Article  Google Scholar 

  6. 6.

    Kolb, H. C. & Sharpless, K. B. The growing impact of click chemistry on drug discovery. Drug Discov. Today 8, 1128–1137 (2003).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  7. 7.

    Moses, J. E. & Moorhouse, A. D. The growing applications of click chemistry. Chem. Soc. Rev. 36, 1249–1262 (2007).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  8. 8.

    Moorhouse, A. D. & Moses, J. E. Click chemistry and medicinal chemistry: a case of ‘cyclo-addiction’. ChemMedChem 3, 715–723 (2008).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  9. 9.

    Thirumurugan, P., Matosiuk, D. & Jozwiak, K. Click chemistry for drug development and diverse chemical–biology applications. Chem. Rev. 113, 4905–4979 (2013).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  10. 10.

    Rouhanifard, S. H., Nordstrom, L. U., Zheng, T. & Wu, P. Chemical probing of glycans in cells and organisms. Chem. Soc. Rev. 42, 4284–4296 (2013).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  11. 11.

    McKay, C. S. & Finn, M. G. Click chemistry in complex mixtures: bioorthogonal bioconjugation. Chem. Biol. 21, 1075–1101 (2014).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  12. 12.

    Xi, W., Scott, T. F., Kloxin, C. J. & Bowman, C. N. Click chemistry in materials science. Adv. Funct. Mater. 24, 2572–2590 (2014).

    CAS  Article  Google Scholar 

  13. 13.

    Liu, Y. et al. Click chemistry in materials synthesis. III. Metal-adhesive polymers from Cu(i)-catalyzed azide–alkyne cycloaddition. J. Polym. Sci. A 45, 5182–5189 (2007).

    CAS  Article  Google Scholar 

  14. 14.

    Diaz, D. D. et al. Click chemistry in materials synthesis. 1. Adhesive polymers from copper-catalyzed azide–alkyne cycloaddition. J. Polym. Sci. A 42, 4392–4403 (2004).

    CAS  Article  Google Scholar 

  15. 15.

    Wu, P. et al. Efficiency and fidelity in a click-chemistry route to triazole dendrimers by the copper(i)-catalyzed ligation of azides and alkynes. Angew. Chem. Int. Ed. 43, 3928–3932 (2004).

    CAS  Article  Google Scholar 

  16. 16.

    van Steenis, D. J. V. C., David, O. R. P., van Strijdonck, G. P. F., van Maarseveen, J. H. & Reek, J. N. H. Click-chemistry as an efficient synthetic tool for the preparation of novel conjugated polymers. Chem. Commun. 2005, 4333–4335 (2005).

    Article  CAS  Google Scholar 

  17. 17.

    Srinivasachari, S., Liu, Y., Zhang, G., Prevette, L. & Reineke, T. M. Trehalose click polymers inhibit nanoparticle aggregation and promote pDNA delivery in serum. J. Am. Chem. Soc. 128, 8176–8184 (2006).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  18. 18.

    Gahtory, D. et al. Quantitative and orthogonal formation and reactivity of SuFEx platforms. Chem. Eur. J. 24, 10550–10556 (2018).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  19. 19.

    Randall, J. D. et al. Modification of carbon fibre surfaces by sulfur–fluoride exchange click chemistry. ChemPhysChem 19, 3176–3181 (2018).

    CAS  Article  Google Scholar 

  20. 20.

    Kassick, A. J. et al. SuFEx-based strategies for the preparation of functional particles and cation exchange resins. Chem. Commun. 55, 3891–3894 (2019).

    CAS  Article  Google Scholar 

  21. 21.

    Fan, H. et al. Sulfur(vi) fluoride exchange polymerization for large conjugate chromophores and functional main-chain polysulfates with nonvolatile memory performance. ChemPlusChem 83, 407–413 (2018).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  22. 22.

    Park, S. et al. SuFEx in metal–organic frameworks: versatile postsynthetic modification tool. ACS Appl. Mater. Interfaces 10, 33785–33789 (2018).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  23. 23.

    Li, S., Wu, P., Moses, J. E. & Sharpless, K. B. Multidimensional SuFEx click chemistry: sequential sulfur(vi) fluoride exchange connections of diverse modules launched from an SOF4 hub. Angew. Chem. Int. Ed. 56, 2903–2908 (2017).

    CAS  Article  Google Scholar 

  24. 24.

    Gao, B., Li, S., Wu, P., Moses, J. E. & Sharpless, K. B. SuFEx chemistry of thionyl tetrafluoride (SOF4) with organolithium nucleophiles: synthesis of sulfonimidoyl fluorides, sulfoximines, sulfonimidamides and sulfonimidates. Angew. Chem. Int. Ed. 57, 1939–1943 (2018).

    CAS  Article  Google Scholar 

  25. 25.

    Zheng, Q., Dong, J. & Sharpless, K. B. Ethenesulfonyl fluoride (ESF): an on-water procedure for the kilogram-scale preparation. J. Org. Chem. 81, 11360–11362 (2016).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  26. 26.

    Smedley, C. J. et al. 1-Bromoethene-1-sulfonyl fluoride (BESF) is another good connective hub for SuFEx click chemistry. Chem. Commun. 54, 6020–6023 (2018).

    CAS  Article  Google Scholar 

  27. 27.

    Leng, J. & Qin, H.-L. 1-Bromoethene-1-sulfonyl fluoride (1-Br-ESF), a new SuFEx clickable reagent, and its application for regioselective construction of 5-sulfonylfluoro isoxazoles. Chem. Commun. 54, 4477–4480 (2018).

    CAS  Article  Google Scholar 

  28. 28.

    Thomas, J. & Fokin, V. V. Regioselective synthesis of fluorosulfonyl 1,2,3-triazoles from bromovinylsulfonyl fluoride. Org. Lett. 20, 3749–3752 (2018).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  29. 29.

    Dong, J., Sharpless, K. B., Kwisnek, L., Oakdale, J. S. & Fokin, V. V. SuFEx-based synthesis of polysulfates. Angew. Chem. Int. Ed. 53, 9466–9470 (2014).

    CAS  Article  Google Scholar 

  30. 30.

    Gao, B. et al. Bifluoride-catalysed sulfur(vi) fluoride exchange reaction for the synthesis of polysulfates and polysulfonates. Nat. Chem. 9, 1083–1088 (2017).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  31. 31.

    Wang, H. et al. SuFEx-based polysulfonate formation from ethenesulfonyl fluoride-amine adducts. Angew. Chem. Int. Ed. 56, 11203–11208 (2017).

    CAS  Article  Google Scholar 

  32. 32.

    Cowie, J. M. G. & Arrighi, V. in Polymers: Chemistry and Physics of Modern Materials 3rd edn (eds Cowie, J. M. G. & Arrighi, V.) 29–56 (CRC Press, 2007).

  33. 33.

    Gauthier, M. A., Gibson, M. I. & Klok, H.-A. Synthesis of functional polymers by post-polymerization modification. Angew. Chem. Int. Ed. 48, 48–58 (2009).

    CAS  Article  Google Scholar 

  34. 34.

    Boaen, N. K. & Hillmyer, M. A. Post-polymerization functionalization of polyolefins. Chem. Soc. Rev. 34, 267–275 (2005).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  35. 35.

    Yatvin, J., Brooks, K. & Locklin, J. SuFEx on the surface: a flexible platform for postpolymerization modification of polymer brushes. Angew. Chem. Int. Ed. 54, 13370–13373 (2015).

    CAS  Article  Google Scholar 

  36. 36.

    Oakdale, J. S., Kwisnek, L. & Fokin, V. V. Selective and orthogonal post-polymerization modification using sulfur(vi) fluoride exchange (SuFEx) and copper-catalyzed azide–alkyne cycloaddition (CuAAC) reactions. Macromolecules 49, 4473–4479 (2016).

    CAS  Article  Google Scholar 

  37. 37.

    Brooks, K. et al. SuFEx postpolymerization modification kinetics and reactivity in polymer brushes. Macromolecules 51, 297–305 (2018).

    Article  CAS  Google Scholar 

  38. 38.

    Hong, Y., Lam, J. W. Y. & Tang, B. Z. Aggregation-induced emission. Chem. Soc. Rev. 40, 5361–5388 (2011).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  39. 39.

    del Amo, D. S. et al. Biocompatible copper(i) catalysts for in vivo imaging of glycans. J. Am. Chem. Soc. 132, 16893–16899 (2010).

    PubMed Central  Article  CAS  Google Scholar 

  40. 40.

    Wang, W. et al. Sulfated ligands for the copper(i)-catalyzed azide–alkyne cycloaddition. Chem. Asian J. 6, 2796–2802 (2011).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  41. 41.

    Yashima, E., Maeda, K., Iida, H., Furusho, Y. & Nagai, K. Helical polymers: synthesis, structures and functions. Chem. Rev. 109, 6102–6211 (2009).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  42. 42.

    Nakano, T. & Okamoto, Y. Synthetic helical polymers: conformation and function. Chem. Rev. 101, 4013–4038 (2001).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  43. 43.

    BIOVIA, Materials Studio 6.0 (Dassault Systems).

  44. 44.

    Li, Y. et al. Hybrids of organic molecules and flat, oxide-free silicon: high-density monolayers, electronic properties and functionalization. Langmuir 28, 9920–9929 (2012).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  45. 45.

    Bose, K., Lech, C. J., Heddi, B. & Anh Tuan, P. High-resolution AFM structure of DNA G-wires in aqueous solution. Nat. Commun. 9, 1959 (2018).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  46. 46.

    Liang, D.-D. et al. Silicon-free SuFEx reactions of sulfonimidoyl fluorides: scope, enantioselectivity and mechanism. Angew. Chem. Int. Ed. 59, 7494–7500 (2020).

    CAS  Article  Google Scholar 

  47. 47.

    Pietschnig, R. Polymers with pendant ferrocenes. Chem. Soc. Rev. 45, 5216–5231 (2016).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

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We acknowledge financial support from the National Science Foundation (CHE-1610987 to K.B.S.), the NIH (R35GM139643 to P.W.), the ARC for Supporting Future Fellowship FT170100156 (J.M.), the Guangdong Natural Science Funds for Distinguished Young Scholar (2018B030306018 to S.L.), the Program for Guangdong Introducing Innovative and Entrepreneurial Teams (2017ZT07C069 to S.L.) and the Pearl River Talent Recruitment Program (2019QN01L111 to S.L.), the National Science Foundation of China (#21871208 to H.Z. and 21971260 to S.L.), King Abdulaziz University (H.D. and H.Z.), and Basic Research Project of leading technology in Jiangsu Province (BK20202012 to J.L.). Part of the work was carried out as a user project at the Molecular Foundry, supported by the Office of Science, Office of Basic Energy Sciences, of the US Department of Energy under contract no. DE-AC02-05CH11231. We thank L. Liang (Shanxi University) for assistance with X-ray single-crystal structural analyses and S. Ruggeri and B. van Lagen (Wageningen University) for detailed AFM analysis. We are grateful to J.R. Cappiello for proofreading and advice on the manuscript.

Author information




K.B.S., J.M. and H.Z. supervised the work. S.L., K.B.S., P.W., J.L. and J.M. conceived and designed the syntheses of the SOF4-derived polymers. S.L., G.L., B.G., S.P.P., X.C. and H.K. performed the synthesis and characterization of the polymers. F.Z., L.M.K., Y.L. and J.L. collected and analysed the DSC and TGA data for all polymers. F.Z. collected the XRD data. S.P.P. performed molecular modelling, AFM and scanning Auger experiments. H.D. performed the SEM and TEM experiments. D.-D.L. collected the circular dichroism data. S.L., H.Z., K.B.S. and J.M. contributed to the preparation of the manuscript. All authors discussed the results and commented on the manuscript.

Corresponding authors

Correspondence to Suhua Li, Peng Wu, Han Zuilhof, John Moses or K. Barry Sharpless.

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Competing interests

K.B.S., P.W., S.L. and B.G. are named as inventors on a patent applicant filed by The Scripps Research Institute (provisional patent application US62/427,489, filed on 29 November 2016, and international patent application no. PCT/US2017/063746).

Additional information

Peer review information Nature Chemistry thanks Jason Locklin, Jia Niu and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information

Supplementary Figs. 1–17, Supplementary procedures and all characterization data, NMR spectra, HPLC chromatogram and Supplementary Table 1.

Supplementary Data

CIF file with structure factors.

Source data

Source Data Fig. 2

Transformation data of –N=SOF2 at the indicated times and calculation details.

Source Data Fig. 3

Intensity (a.u.) data (11 groups for water content vol% of 0–99%) from wavelength 370 nm to 570 nm.

Source Data Fig. 4

Figure 4c AFM profile.

Source Data Fig. 4

Figure 4f Amplitude profile.

Source Data Fig. 4

Figure 4g FFT amplitude.

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Li, S., Li, G., Gao, B. et al. SuFExable polymers with helical structures derived from thionyl tetrafluoride. Nat. Chem. 13, 858–867 (2021).

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