Metronidazole (MTZ) interacts with DNA and causes loss of helical DNA structure and strand break in susceptible organisms. The complexation of metronidazole with copper fits the ligand in a three-dimensional structure, which may allow functional groups to be coupled to specific molecular targets. In this work, the Cu-MTZ complex (CMC) with the molecular formula of [Cu(MTZ)2(MeOH)2](NO3)2 was prepared and characterized by UV–vis, FT-IR, CHN analyzer, and thermogravimetric analysis (TG-DTA) methods. The oxidative stress and toxicity of the CMC were studied on various cancer cell lines. The results showed that the CMC complex is more cytotoxic than MTZ, while the induced oxidative stress in human carcinoma cell lines was comparable with MTZ. By using voltammetry (cyclic voltammetry, differential pulse voltammetry), spectroscopy (UV–vis, fluorescence, FT-IR spectroscopy), and docking and molecular dynamic techniques the binding mode of the CMC to DNA was also evaluated. The stability constants of the CMC complex with DNA at 25 °C were 5.20 × 10+3 and 3.50 × 10+3, evidenced by spectroscopy and voltammetry, respectively. All data proved the greater affinity of CMC to DNA rather than the MTZ. The CMC intercalated to DNA in two modes: hydrophobic and electrostatic forces. The greater affinity to the DNA may confirm the large increase in the cytotoxicity activity of the CMC complex.

中文翻译：

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合成的铜-甲硝唑复合物的 DNA 结合见解，实验和计算机评估


甲硝唑 （MTZ） 与 DNA 相互作用，导致易感生物体螺旋 DNA 结构丢失和链断裂。甲硝唑与铜的络合使配体形成三维结构，这可能允许官能团偶联到特定的分子靶标上。本工作制备了分子式为 [Cu（MTZ）2（MeOH）2]（NO3）2 的 Cu-MTZ 络合物 （CMC），并通过紫外-可见分光光度、FT-IR、CHN 分析仪和热重分析 （TG-DTA） 方法进行了表征。在各种癌细胞系上研究了 CMC 的氧化应激和毒性。结果表明，CMC 复合物比 MTZ 更具细胞毒性，而在人癌细胞系中诱导的氧化应激与 MTZ 相当。通过使用伏安法 （循环伏安法、差分脉冲伏安法）、光谱法 （紫外-可见光、荧光、FT-IR 光谱法） 以及对接和分子动力学技术，还评估了 CMC 与 DNA 的结合模式。光谱学和伏安法分别证明 25 °C 下 DNA 与 DNA 的 CMC 复合物的稳定性常数分别为 5.20 × 10+3 和 3.50 × 10+3。所有数据都证明了 CMC 对 DNA 的亲和力高于 MTZ。CMC 以两种模式嵌入 DNA：疏水力和静电力。对 DNA 的亲和力更大可能证实 CMC 复合物的细胞毒性活性大幅增加。