TY - JOUR
T1 - A Thermally Stable SO2-Releasing Mechanophore
T2 - Facile Activation, Single-Event Spectroscopy, and Molecular Dynamic Simulations
AU - Sun, Yunyan
AU - Neary, William J.
AU - Huang, Xiao
AU - Kouznetsova, Tatiana B.
AU - Ouchi, Tetsu
AU - Kevlishvili, Ilia
AU - Wang, Kecheng
AU - Chen, Yingying
AU - Kulik, Heather J.
AU - Craig, Stephen L.
AU - Moore, Jeffrey S.
N1 - This work was supported by the NSF Center for the Chemistry of Molecularly Optimized Networks (MONET), CHE-2116298. The authors thank Toby Woods for collecting crystal data, Dorothy Loudermilk for graphic assistance. Thermogravimetric analysis experiments were carried out in the Materials Research Laboratory Central Research Facilities, University of Illinois.
PY - 2024/4/17
Y1 - 2024/4/17
N2 - 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.
AB - 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.
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U2 - 10.1021/jacs.4c02139
DO - 10.1021/jacs.4c02139
M3 - Article
C2 - 38581383
AN - SCOPUS:85189781168
SN - 0002-7863
VL - 146
SP - 10943
EP - 10952
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 15
ER -