Force-Induced Reversal of β-Eliminations: Stressed Disulfide Bonds in Alkaline Solution
Force-Induced Reversal of β-Eliminations: Stressed Disulfide Bonds in Alkaline Solution
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DOI：
10.1002/anie.201508005
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发表时间：
2016-01-22
影响因子：
16.6
通讯作者：
Marx, Dominik
中科院分区：
文献类型：
--
作者：
Dopieralski, Przemyslaw;Ribas-Arino, Jordi;Marx, Dominik
了解拉力对二硫键断裂的影响不仅对硫化材料（如应变橡胶）中交联剂的断裂至关重要，而且对二硫开关对蛋白质活性的调节也至关重要。通过在凝聚相中进行从头算模拟，我们研究了β -消除法解理二硫化物对机械应力的响应。我们揭示了热反应的速率决定的第一步，这是β质子的抽象，是不敏感的外力。然而，研究发现，大于1nn的力极大地改变了反应的自由能格局，从而产生了第二个通道，在这个通道中，反应步骤的顺序颠倒了，将β -去质子化变成了C-S裂解的无障碍后续过程。这将一个缓慢的、与力无关的二级动力学过程转变为一个单分子反应，它被机械力大大加速。
Understanding the impact of tensile forces on disulfide bond cleavage is not only crucial to the breaking of cross-linkers in vulcanized materials such as strained rubber, but also to the regulation of protein activity by disulfide switches. By using ab initio simulations in the condensed phase, we investigated the response of disulfide cleavage by beta-elimination to mechanical stress. We reveal that the rate-determining first step of the thermal reaction, which is the abstraction of the beta-proton, is insensitive to external forces. However, forces larger than about 1 nN were found to reshape the free-energy landscape of the reaction so dramatically that a second channel is created, where the order of the reaction steps is reversed, turning beta-deprotonation into a barrier-free follow-up process to C-S cleavage. This transforms a slow and force-independent process with second-order kinetics into a unimolecular reaction that is greatly accelerated by mechanical forces.