Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Build. 9, 1113 Sofia, Bulgaria.
Department of Organic Synthesis, University of Chemical Technology and Metallurgy, 8 Kliment Ohridski Blvd., 1756 Sofia, Bulgaria.
Spectrochim Acta A Mol Biomol Spectrosc. 2020 Jun 15;234:118279. doi: 10.1016/j.saa.2020.118279. Epub 2020 Mar 19.
The conversion of N,N'-disubstituted hydrazone derivatives of 5-nitrobenzimidazole-2-thione into radical anion and dianion products was studied through infrared (IR) spectroscopy and computational methods. The electrochemical reduction of 3,3'-(5-nitro-2-thioxo-1H-benzo[d]imidazole-1,3(2H)-diyl)bis(N'-(2-methoxybenzylidene))propane-hydrazide was performed directly in the IR cell and the spectral changes were monitored over time in order to identify the spectral bands originating from the reduction product. In order to clarify whether the reduction leads to the generation of radical anion or deprotonated radical dianion, a second spectroscopic experiment was carried out where deprotonation was achieved by treatment with sodium methoxide. Both experiments resulted in distinctly different spectral features, giving evidence that the reduction to radical anion is not accompanied by deprotonation. In order to explain the experimentally observed differences in the hepatotoxicity within the series of N,N'-disubstituted derivatives of 5-nitrobenzimidazole-2-thione, several molecular electronic parameters such as frontier molecular orbitals, spin and charge distribution over fragments, and electron affinities of the studied hydrazone derivatives were compared to those of a previously studied ester derivative. Based on the estimated electronic parameters, it was shown that the type of the side chains (ester, hydrazone etc.) attached to the N-atoms in the nitrobenzimidazole derivatives do not change significantly the propensity of the compounds towards nitro reduction, but however the generated radical anions are characterized by different reactivity accounting for the different hepatotoxicity.
通过红外（IR）光谱和计算方法研究了 N,N'-取代的 5-硝基苯并咪唑-2-硫酮腙衍生物转化为自由基阴离子和二阴离子产物。直接在 IR 池内进行 3,3'-(5-硝基-2-硫代-1H-苯并[d]咪唑-1,3(2H)-二基)双(N'-(2-甲氧基亚苄基))丙烷-腙的电化学还原，并随时间监测光谱变化，以识别源于还原产物的光谱带。为了澄清还原是否导致生成自由基阴离子或去质子化的自由基二阴离子，进行了第二次光谱实验，其中通过用甲醇钠处理实现去质子化。两个实验都产生了明显不同的光谱特征，证明还原为自由基阴离子不伴随去质子化。为了解释在 N,N'-取代的 5-硝基苯并咪唑-2-硫酮腙衍生物系列中观察到的肝毒性差异，比较了几个分子电子参数，如前线分子轨道、碎片上的自旋和电荷分布以及研究的腙衍生物的电子亲和能，与先前研究的酯衍生物进行了比较。基于估计的电子参数，表明侧链的类型（酯、腙等）与硝基苯并咪唑衍生物中的 N 原子相连，不会显著改变化合物对硝基还原的倾向，但生成的自由基阴离子具有不同的反应性，这解释了不同的肝毒性。
