Pokidova Olesya V, Novikova Veronika O, Emel'yanova Nina S, Kormukhina Alexandra Yu, Kulikov Alexander V, Utenyshev Andrey N, Lazarenko Vladimir A, Ovanesyan Nikolai S, Starostina Arina A, Sanina Natalya A
Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, prosp. Akad. Semenova, 1., 142432 Chernogolovka, Moscow region, Russian Federation.
Faculty of Fundamental Physical and Chemical Engineering, Lomonosov Moscow State University M.V. Lomonosov, Leninskie gory, 1., 119991 Moscow, Russian Federation.
Dalton Trans. 2023 Feb 28;52(9):2641-2662. doi: 10.1039/d2dt04047f.
In this work, a new binuclear nitrosyl complex with 3.4-dichlorothiophenolyl ligands [Fe(SCHCl)(NO)] has been synthesized. Nitrosyl iron complexes (NICs) are systems for the storage and delivery of NO in the body. There is a dynamic equilibrium between dinitrosyl iron units bound to low molecular weight ligands and high molecular weight (protein) ligands . From this point of view, the transformation of the studied complex in DMSO and buffer, as well as in biological systems, has been analyzed. In DMSO, it decomposes into mononuclear NICs, which quickly decay in buffer solutions with NO release. The high molecular weight product is formed as a result of the binding of the complex to bovine serum albumin (the Stern-Volmer constant is 2.1 × 10 M). In this case, the complex becomes a prolonged NO-donor. Such a long-term effect has been observed for the first time. Similarly, in a system with oxyhemoglobin, NO generation is slower; the UV-vis spectra show a gradual formation of methemoglobin. On the other hand, reduced glutathione has little effect on the NO-donor properties of the complex despite the fact that ligand substitution is observed in the system and a binuclear product is formed. Mucin binds the complex, and the decomposition mechanism is different from that for buffer solutions. Thus, these proteins and glutathione are able to participate in the transformation of the complex and modulate its properties as a potential drug.
在本研究中，合成了一种具有3,4 - 二氯苯硫酚配体的新型双核亚硝酰配合物[Fe(SCHCl)(NO)]。亚硝酰铁配合物（NICs）是体内一氧化氮（NO）储存和释放的体系。与低分子量配体和高分子量（蛋白质）配体结合的二亚硝酰铁单元之间存在动态平衡。从这一角度出发，分析了所研究的配合物在二甲基亚砜（DMSO）、缓冲液以及生物体系中的转化情况。在DMSO中，它分解为单核NICs，后者在缓冲溶液中迅速衰变并释放出NO。高分子量产物是该配合物与牛血清白蛋白结合的结果（斯特恩 - 沃尔默常数为2.1×10 M）。在这种情况下，该配合物成为一种长效NO供体。这种长期效应首次被观察到。类似地，在与氧合血红蛋白的体系中，NO的生成较慢；紫外 - 可见光谱显示高铁血红蛋白逐渐形成。另一方面，尽管在体系中观察到配体取代并形成了双核产物，但还原型谷胱甘肽对该配合物的NO供体性质影响不大。粘蛋白会结合该配合物，其分解机制与缓冲溶液中的不同。因此，这些蛋白质和谷胱甘肽能够参与配合物的转化并调节其作为潜在药物的性质。
