DataSheet3_Dithiocarbazate ligands and their Ni(II) complexes with potential biological activity: Structural, antitumor and molecular docking study.PDF

In the search for new metal complexes with antitumor potential, two dithiocarbazate ligands derived from 1,1,1-trifluoro-2,4-pentanedione (H2L1) and (H2L2) and four Ni(II) complexes, [Ni(L1)PPh3] (1), [Ni(L1)Py] (2), [Ni(L2)PPh3] (3), and [Ni(L2)Py] (4), were successfully synthesized and investigated by physical-chemistry and spectroscopic methods. The crystal structure of the H2L1 and the Ni(II) complexes has been elucidated by single-crystal X-ray diffraction. The obtained structure from H2L1 confirms the cyclization reaction and formation of the pyrazoline derivative. The results showed square planar geometry to the metal centers, in which dithiocarbazates coordinated by the ONS donor system and a triphenylphosphine or pyridine molecule complete the coordination sphere. Hirshfeld surface analysis by dnorm function was investigated and showed π–π stacking interactions upon the molecular packing of H2L1 and non-classical hydrogen bonds for all compounds. Fingerprint plots showed the main interactions attributed to H⋅H C⋅H, O⋅H, Br⋅H, and F⋅H, with contacts contributing between 1.9% and 38.2%. The mass spectrometry data indicated the presence of molecular ions [M + H]+ and characteristic fragmentations of the compounds, which indicated the same behavior of the compounds in solution and solid state. Molecular docking simulations were studied to evaluate the properties and interactions of the free dithiocarbazates and their Ni(II) complexes with selected proteins and DNA. These results were supported by in vitro cytotoxicity assays against four cancer cell lines, showing that the synthesized metal complexes display promising biological activity.

为筛选具有抗肿瘤潜力的新型金属配合物，本研究以1,1,1-三氟-2,4-戊二酮（1,1,1-trifluoro-2,4-pentanedione）为原料合成了两种二硫代卡巴腙（dithiocarbazate）配体H₂L₁与H₂L₂，并成功制备了四种镍(II)配合物：[Ni(L₁)PPh₃] (1)、[Ni(L₁)Py] (2)、[Ni(L₂)PPh₃] (3)以及[Ni(L₂)Py] (4)，随后通过物理化学及光谱学方法对其进行了系统表征。通过单晶X射线衍射（single-crystal X-ray diffraction）解析了配体H₂L₁及全部镍(II)配合物的晶体结构，其中H₂L₁的结构验证了环化反应的发生及吡唑啉衍生物的生成。结果表明，金属中心均呈现平面正方形配位构型：二硫代卡巴腙配体通过ONS给体体系参与配位，外加一个三苯基膦（triphenylphosphine，PPh₃）或吡啶（pyridine，Py）分子即可完成配位球结构。采用dnorm函数开展希尔施菲尔德（Hirshfeld）表面分析，结果显示：配体H₂L₁的分子堆积过程中存在π-π堆积相互作用，所有受试化合物均存在非经典氢键相互作用。指纹图谱显示，主要相互作用类型包括H⋅H、C⋅H、O⋅H、Br⋅H及F⋅H接触，各类接触的贡献占比介于1.9%至38.2%之间。质谱数据显示，所有化合物均检出分子离子峰[M + H]⁺及特征碎裂峰，表明此类化合物在溶液与固态下的行为具有一致性。本研究开展了分子对接模拟（molecular docking simulations），以评估游离二硫代卡巴腙配体及其镍(II)配合物与选定蛋白及DNA的相互作用与相关性质。针对四种癌细胞系的体外细胞毒性实验验证了上述结果，表明所合成的金属配合物具备良好的抗肿瘤生物活性潜力。