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, Jeffrey S. Moore

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)10943-10952
Number of pages10
JournalJournal of the American Chemical Society
Volume146
Issue number15
DOIs
StatePublished - Apr 17 2024

ASJC Scopus subject areas

  • Catalysis
  • General Chemistry
  • Biochemistry
  • Colloid and Surface Chemistry

Fingerprint

Dive into the research topics of 'A Thermally Stable SO2-Releasing Mechanophore: Facile Activation, Single-Event Spectroscopy, and Molecular Dynamic Simulations'. Together they form a unique fingerprint.

Cite this