Cell-Penetrating Dynamic-Covalent Benzopolysulfane Networks

Yangyang Cheng, Lili Zong, Javier López-Andarias, Eline Bartolami, Yasunori Okamoto, Thomas R. Ward, Naomi Sakai, Stefan Matile

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)


Cyclic oligochalcogenides (COCs) are emerging as promising systems to penetrate cells. Clearly better than and different to the reported diselenolanes and epidithiodiketopiperazines, we introduce the benzopolysulfanes (BPS), which show efficient delivery, insensitivity to inhibitors of endocytosis, and compatibility with substrates as large as proteins. This high activity coincides with high reactivity, selectively toward thiols, exceeding exchange rates of disulfides under tension. The result is a dynamic-covalent network of extreme sulfur species, including cyclic oligomers, from dimers to heptamers, with up to nineteen sulfurs in the ring. Selection from this unfolding adaptive network then yields the reactivities and selectivities needed to access new uptake pathways. Contrary to other COCs, BPS show high retention on thiol affinity columns. The identification of new modes of cell penetration is important because they promise new solutions to challenges in delivery and beyond.

Original languageEnglish
Pages (from-to)9522-9526
Number of pages5
JournalAngewandte Chemie - International Edition
Issue number28
Publication statusPublished - 2019 Jul 8
Externally publishedYes


  • adaptive networks
  • cellular uptake
  • cyclic oligochalcogenides
  • dynamic-covalent chemistry
  • polysulfanes

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)


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