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Cell‐Penetrating Dynamic‐Covalent Benzopolysulfane Networks
Author(s) -
Cheng Yangyang,
Zong Lili,
LópezAndarias Javier,
Bartolami Eline,
Okamoto Yasunori,
Ward Thomas R.,
Sakai Naomi,
Matile Stefan
Publication year - 2019
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201905003
Subject(s) - covalent bond , thiol , chemistry , combinatorial chemistry , endocytosis , cell , biophysics , nanotechnology , biochemistry , materials science , organic chemistry , biology
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.