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 () motif that releases one equivalent of sulfur dioxide (SO) from each repeat unit. The 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 SO released per 143.3 kDa chain. We quantified the mechanochemical reactivity of by single-molecule force spectroscopy and resolved its single-event activation. The force-coupled rate constant for opening reaches ∼9.0 s at ∼1520 pN, and each reaction of a single domain releases a stored length of ∼0.68 nm. We investigated the mechanism of activation using ab initio steered molecular dynamic simulations and rationalized the observed stereoselectivity. These comprehensive studies of the mechanophore provide a mechanically coupled mechanism of multi-SO release from one polymer chain, facilitating the translation of polymer mechanochemistry to potential biomedical applications.
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