<i>In silico</i> and <i>in vitro</i> studies of transition metal complexes derived from curcumin–isoniazid Schiff base

A series of transition metal complexes have been synthesized from biologically active curcumin and isoniazid Schiff base. They are characterized by various spectral techniques like UV–Vis, Fourier transform infrared (FT-IR), nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR) and mass spectroscopies. Moreover, elemental analysis, magnetic susceptibility and molar conductivity measurements are also carried out. All these data evidence that the metal complexes acquire square planar except zinc(II) which adopts a tetrahedral geometry, and they are non-electrolytic in nature. Groove mode of binding between the calf thymus DNA (CT DNA) and metal complexes is confirmed by electronic absorption titration, viscosity and cyclic voltammetry studies. In addition to that, all the metal complexes are able to cleave pUC 19 DNA. Optimized geometry and ground-state electronic structure calculations of all the synthesized compounds are established out by density functional theory (DFT) using B3LYP method which theoretically reveals that copper(II) complex explores higher stability and higher biological accessibility. This is experimentally corroborated by antimicrobial studies. <i>In silico</i> Absorption, Distribution, Metabolism, Excretion (ADME) studies reveal the biological potential of all synthesized complexes, and also biological activity of the ligand is predicted by PASS online biological activity prediction software. Molecular docking studies are also carried out to confirm the groove mode of binding and receptor–complex interactions. Communicated by Ramaswamy H. Sarma研究人员以具有生物活性的姜黄素（curcumin）与异烟肼希夫碱为原料，合成了一系列过渡金属配合物。采用紫外-可见（UV–Vis）光谱、傅里叶变换红外（Fourier transform infrared, FT-IR）光谱、核磁共振（nuclear magnetic resonance, NMR）、电子顺磁共振（electron paramagnetic resonance, EPR）及质谱等多种光谱技术对其进行表征，同时开展了元素分析、磁化率与摩尔电导率测定实验。 上述所有表征数据均证实：除锌(II)配合物采取四面体构型外，其余金属配合物均为平面正方形结构，且整体呈非电解质特性。通过电子吸收滴定、粘度法及循环伏安法研究，证实了小牛胸腺DNA（calf thymus DNA, CT DNA）与金属配合物之间以沟槽模式结合。此外，所有金属配合物均能切割pUC 19质粒DNA。 采用基于B3LYP泛函的密度泛函理论（density functional theory, DFT），对所有合成化合物的优化几何构型与基态电子结构进行了计算，理论结果表明铜(II)配合物具有更高的稳定性与生物可及性，该结论得到了抗菌实验的佐证。计算机模拟（In silico）的吸收、分布、代谢、排泄（Absorption, Distribution, Metabolism, Excretion, ADME）研究揭示了所有合成配合物的生物活性潜力，同时通过PASS在线生物活性预测软件预测了配体的生物活性。此外还开展了分子对接研究，以进一步验证沟槽结合模式及受体-配合物相互作用。本文由Ramaswamy H. Sarma通讯。