A Thermally Stable SO2-Releasing Mechanophore: Facile Activation, Single-Event Spectroscopy, and Molecular Dynamic Simulations,Journal of the American Chemical Society

当前位置： X-MOL 学术 › J. Am. Chem. Soc. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

A Thermally Stable SO2-Releasing Mechanophore: Facile Activation, Single-Event Spectroscopy, and Molecular Dynamic Simulations
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2024-04-06 , DOI: 10.1021/jacs.4c02139
Yunyan Sun _{1,

2} , William J Neary _{1,

2} , Xiao Huang ₃ , Tatiana B Kouznetsova ₄ , Tetsu Ouchi ₄ , Ilia Kevlishvili ₅ , Kecheng Wang ₁ , Yingying Chen _{2,

6} , Heather J Kulik _{3,

5} , Stephen L Craig ₄ , Jeffrey S Moore _{1,

2}

Affiliation

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.

中文翻译：

热稳定的 SO2 释放机械载体：轻松激活、单粒子光谱和分子动态模拟

响应机械力释放小分子的聚合物是作为下一代按需输送系统的有希望的候选者。尽管通过仔细的分子设计释放多种有效载荷的机械载体的开发取得了进展，但能够大量释放具有生物医学意义的货物的支架仍然很少。在本报告中，我们详细介绍了一种由 8-噻二环[3.2.1]辛烷 8,8-二氧化物 ( TBO ) 基序构建的不可裂机械载体，该基序从每个重复单元释放一当量的二氧化硫 (SO ₂ )。 TBO机械载体表现出高热稳定性，但在有机溶剂或水介质中使用溶液超声处理进行机械化学活化，效率高达 63%，相当于每条 143.3 kDa 链释放 206 个 SO ₂分子。我们通过单分子力谱量化了TBO的机械化学反应性，并解决了其单事件激活问题。 TBO打开的力耦合速率常数在 ~1520 pN 时达到 ~9.0 s ^–1 ，并且单个TBO域的每个反应释放存储的长度 ~0.68 nm。我们使用从头开始的分子动力学模拟研究了TBO活化的机制，并对观察到的立体选择性进行了合理化。这些对TBO机械力团的综合研究提供了一种从一个聚合物链释放多 SO ₂的机械耦合机制，促进了聚合物机械力化学向潜在生物医学应用的转化。

更新日期：2024-04-06

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南