A Thermally Stable SO2-Releasing Mechanophore: Facile Activation, Single-Event Spectroscopy, and Molecular Dynamic Simulations
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Accepted version
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Author(s)
Sun, Yunyan
Neary, William J
Huang, Xiao
Kouznetsova, Tatiana B
Ouchi, Tetsu
Kevlishvili, Ilia
Wang, Kecheng
Chen, Yingying
Kulik, Heather J
Craig, Stephen L
Date Issued
April 6, 2024
Journal
Journal of the American Chemical Society
Publisher
American Chemical Society
Citation
A Thermally Stable SO2-Releasing Mechanophore: Facile Activation, Single-Event Spectroscopy, and Molecular Dynamic Simulations. Yunyan Sun, William J. Neary, Xiao Huang, Tatiana B. Kouznetsova, Tetsu Ouchi, Ilia Kevlishvili, Kecheng Wang, Yingying Chen, Heather J. Kulik, Stephen L. Craig, and Jeffrey S. Moore. Journal of the American Chemical Society 2024 146 (15), 10943-10952.
Version
Author's final manuscript
Abstract
Polymers that release small molecules in response to mechanical force are promising candidates as next-generation on-demand delivery systems. Despite advancements in the development of mechanophores for releasing diverse payloads through careful molecular design, the availability of scaffolds capable of discharging biomedically significant cargos in substantial quantities remains scarce. In this report, we detail a nonscissile mechanophore built from an 8-thiabicyclo[3.2.1]octane 8,8-dioxide (TBO) motif that releases one equivalent of sulfur dioxide (SO2) from each repeat unit. The TBO mechanophore exhibits high thermal stability but is activated mechanochemically using solution ultrasonication in either organic solvent or aqueous media with up to 63% efficiency, equating to 206 molecules of SO2 released per 143.3 kDa chain. We quantified the mechanochemical reactivity of TBO by single-molecule force spectroscopy and resolved its single-event activation. The force-coupled rate constant for TBO opening reaches ∼9.0 s–1 at ∼1520 pN, and each reaction of a single TBO domain releases a stored length of ∼0.68 nm. We investigated the mechanism of TBO activation using ab initio steered molecular dynamic simulations and rationalized the observed stereoselectivity. These comprehensive studies of the TBO mechanophore provide a mechanically coupled mechanism of multi-SO2 release from one polymer chain, facilitating the translation of polymer mechanochemistry to potential biomedical applications.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Massachusetts Institute of Technology. Department of Chemical Engineering
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DOI of Published Version
https://doi.org/10.1021/jacs.4c02139
