Copper ion vs copper metal-organic framework catalyzed NO release from bioavailable S-Nitrosoglutathione en route to biomedical applications: Direct 1H NMR monitoring in water allowing identification of the distinct, true reaction stoichiometries and thio
Copper ion vs copper metal-organic framework catalyzed NO release from bioavailable S-Nitrosoglutathione en route to biomedical applications: Direct 1H NMR monitoring in water allowing identification of the distinct, true reaction stoichiometries and thio
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DOI：
10.1016/j.jinorgbio.2019.110760
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发表时间：
2019-10
影响因子：
3.9
通讯作者：
Robert R. Tuttle;Heather N. Rubin;C. Rithner;R. Finke;Melissa M. Reynolds
中科院分区：
文献类型：
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作者：
Robert R. Tuttle;Heather N. Rubin;C. Rithner;R. Finke;Melissa M. Reynolds
含铜化合物在谷胱甘肽（GSH）存在下催化s -亚硝基谷胱甘肽（GSNO）分解，生成谷胱甘肽二硫（GSSG）和一氧化氮（NO）。从内源性来源产生延伸的NO在医学上是理想的，可以实现血管舒张，减少医疗器械上的生物膜和抗菌活性。均相和非均相铜催化内源性GSNO释放NO。金属-有机骨架（MOF） H3[(Cu4Cl)3-(BTTri)8, H3BTTri = 1,3,5-tris（1h -1,2,3-三唑-5-基）苯]（CuBTTri）是血浆中用于GSNO分解的一种多相催化剂。尽管这些系统在生物医学上有应用，但关于它们的基本问题仍然没有答案，部分原因是以前没有方法可以同时跟踪水中的[GSNO]， [GSH]和[GSSG]。追踪水中的这些反应是研究生物介质（血液中大约80%是水）中NO释放系统必须运行的必要步骤。铜离子和cuttri催化GSNO分解的平衡化学计量仍然未知。在此，我们报道了一种直接1h NMR方法：同时监测水中的[GSNO]， [GSH]和[GSSG]；提供了铜离子与cuttri催化GSNO分解的实验测定的化学计量；结果表明，在不添加GSH的情况下，cutri催化的GSNO分解率为10%(16 h)，而在不添加GSH的情况下，铜离子催化的GSNO分解率为100%(16 h)；在cuttri催化反应中加入GSH后，GSNO分解率达到100%。这些观察结果提供了证据，证明铜离子和CuBTTri催化水中GSNO分解通过不同的反应机制运作，现在可以通过1h NMR动力学和其他必要的研究来探索其细节。
Copper containing compounds catalyze decomposition ofS-Nitrosoglutathione (GSNO) in the presence of glutathione (GSH) yielding glutathione disulfide (GSSG) and nitric oxide (NO). Extended NO generation from an endogenous source is medically desirable to achieve vasodilation, reduction in biofilms on medical devices, and antibacterial activity. Homogeneous and heterogeneous copper species catalyze release of NO from endogenous GSNO. One heterogeneous catalyst used for GSNO decomposition in blood plasma is the metal-organic framework (MOF), H3[(Cu4Cl)3-(BTTri)8, H3BTTri = 1,3,5-tris(1H-1,2,3-triazol-5-yl) benzene] (CuBTTri). Fundamental questions about these systems remain unanswered, despite their use in biomedical applications, in part because no method previously existed for simultaneous tracking of [GSNO], [GSH], and [GSSG] in water. Tracking these reactions in water is a necessary step towards study in biological media (blood is approximately 80% water) where NO release systems must operate. Even the balanced stoichiometry remains unknown for copper-ion and CuBTTri catalyzed GSNO decomposition. Herein, we report a direct1H NMR method which: simultaneously monitors [GSNO], [GSH], and [GSSG] in water; provides the experimentally determined stoichiometry for copper-ion vs CuBTTri catalyzed GSNO decomposition; reveals that the CuBTTri-catalyzed reaction reaches 10% GSNO decomposition (16 h) without added GSH, yet the copper-ion catalyzed reaction reaches 100% GSNO decomposition (16 h) without added GSH; and shows 100% GSNO decomposition upon addition of stoichiometric GSH to the CuBTTri catalyzed reaction. These observations provide evidence that copper-ion and CuBTTri catalyzed GSNO decomposition in water operate through different reaction mechanisms, the details of which can now be probed by1H NMR kinetics and other needed studies.