Computational Insights into the Mechanism of Nitric Oxide Generation from S-Nitrosoglutathione Catalyzed by a Copper Metal-Organic Framework.
Computational Insights into the Mechanism of Nitric Oxide Generation from S-Nitrosoglutathione Catalyzed by a Copper Metal-Organic Framework.
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DOI：
10.1021/jacs.3c01569
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发表时间：
2023-05
影响因子：
15
通讯作者：
Benjamin J G Rousseau;A. Soudackov;Robert R. Tuttle;Melissa M. Reynolds;R. Finke;S. Hammes‐Schiffer
中科院分区：
文献类型：
--
作者：
Benjamin J G Rousseau;A. Soudackov;Robert R. Tuttle;Melissa M. Reynolds;R. Finke;S. Hammes‐Schiffer
由于NO的血管舒张和其他有益性质，从内源性来源如S-亚硝基谷胱甘肽（GSNO）控制产生一氧化氮（NO）对生物医学植入物具有重要意义。3-三唑-5-基]苯已显示在水溶液以及血液中催化从GSNO产生NO和谷胱甘肽二硫化物（GSSG）。以前的实验工作提供了2GSNO → 2NO + GSSG反应的催化动力学数据，导致各种建议的机制。在这里，这个催化过程中使用密度泛函理论进行检查。最小功能模型的铜-MOF簇和谷胱甘肽部分的建立，并探讨了三种不同的催化机制。研究的最有利的机制与先前的实验结果一致。该机制涉及GSNO通过硫而不是氮与铜的配位，并且需要产生Cu（I）中间体的还原消除，涉及氧化还原活性铜位点。实验观察到的反应性在高pH值的抑制解释在三唑连接，这降低了Cu（I）中间体的结构稳定性的去质子化。这些基本的机理见解可以普遍适用于用于NO生成的其他MOF催化剂。
The controlled generation of nitric oxide (NO) from endogenous sources, such as S-nitrosoglutathione (GSNO), has significant implications for biomedical implants due to the vasodilatory and other beneficial properties of NO. The water-stable metal-organic framework (MOF) Cu-1,3,5-tris[1H-1,2,3-triazol-5-yl]benzene has been shown to catalyze the production of NO and glutathione disulfide (GSSG) from GSNO in aqueous solution as well as in blood. Previous experimental work provided kinetic data for the catalysis of the 2GSNO → 2NO + GSSG reaction, leading to various proposed mechanisms. Herein, this catalytic process is examined using density functional theory. Minimal functional models of the Cu-MOF cluster and glutathione moieties are established, and three distinct catalytic mechanisms are explored. The most thermodynamically favorable mechanism studied is consistent with prior experimental findings. This mechanism involves coordination of GSNO to copper via sulfur rather than nitrogen and requires a reductive elimination that produces a Cu(I) intermediate, implicating a redox-active copper site. The experimentally observed inhibition of reactivity at high pH values is explained in terms of deprotonation of a triazole linker, which decreases the structural stability of the Cu(I) intermediate. These fundamental mechanistic insights may be generally applicable to other MOF catalysts for NO generation.