Theoretical and experimental investigation of mixed-ligand metal(II) Schiff base complexes using maleic acid as the auxiliary ligand

This work is focused on the synthesis of several transition metal complexes [ML(MA)], where M = Copper (II), Zinc (II), Cobalt (II) and Nickel (II), MA = maleic acid and L = Schiff base generated from benzene-1,2-diamine [<i>o-</i>phenylenediamine] and 4-chlorobenzaldehyde. The characterization using Fourier-Transform Infrared, Nuclear Magnetic Resonance spectroscopy, Ultraviolet-Visible spectra, Mass, Electro Paramagnetic Resonance and elemental analysis confirm the square planar geometry of the complexes. The <i>in vitro</i> antimicrobial potential of the complexes has been tested by the broth dilution method and the antioxidant method has been done by free radical scavenging analysis. The <i>in vitro</i> methods reveal the outstanding biological characteristics of the copper complexes. The molecular structure of the ligand and its metal (II) complexes has been optimized using Density Functional Theory studies performed by the Gaussian-09 software and their parameters have been discussed. Natural Bond Orbital and Frontier Molecular Orbital analyses have assessed the presence of a metal-ligand bond in complexes. In addition, molecular docking studies have also been performed on antiviral activity of all the complexes using a viral protein and their interacting amino acids. All the metal complexes have the strong tendency to undergo intercalation mode of binding with CT DNA.The optimized geometry and the quantum mechanical examinations are carried out using Gaussian 09W software.The docking of synthesized compounds with SARS-CoV-2 receptor 7ACS protease 7AEH represents the docking of metal complexes.In silico and in vitro analyses of the synthesized compounds. All the metal complexes have the strong tendency to undergo intercalation mode of binding with CT DNA. The optimized geometry and the quantum mechanical examinations are carried out using Gaussian 09W software. The docking of synthesized compounds with SARS-CoV-2 receptor 7ACS protease 7AEH represents the docking of metal complexes. In silico and in vitro analyses of the synthesized compounds.

本研究聚焦于多种过渡金属配合物[ML(MA)]的合成，其中M为铜(II)、锌(II)、钴(II)和镍(II)，MA为马来酸，L为由苯-1,2-二胺[邻苯二胺（o-phenylenediamine）]与4-氯苯甲醛缩合得到的希夫碱（Schiff base）。通过傅里叶变换红外光谱（Fourier-Transform Infrared）、核磁共振波谱（Nuclear Magnetic Resonance spectroscopy）、紫外-可见光谱（Ultraviolet-Visible spectra）、质谱、电子顺磁共振（Electron Paramagnetic Resonance）及元素分析对配合物进行表征，证实其具有平面正方形几何构型。采用肉汤稀释法测试了配合物的体外（in vitro）抗菌活性，并通过自由基清除分析开展抗氧化活性检测。体外实验结果表明，铜基配合物展现出优异的生物学特性。采用Gaussian-09软件完成的密度泛函理论（Density Functional Theory）计算对配体及其金属(II)配合物的分子结构进行了优化，并对其结构参数进行了讨论。自然键轨道（Natural Bond Orbital）分析与前线分子轨道（Frontier Molecular Orbital）分析证实了配合物中金属-配体键的存在。此外，本研究还以病毒蛋白及其相互作用氨基酸为靶点，针对所有配合物的抗病毒活性开展了分子对接（molecular docking）研究。所有金属配合物均具有与小牛胸腺DNA（CT DNA）以插入模式结合的强倾向性。采用Gaussian 09W软件完成了优化几何构型与量子力学表征。合成化合物与SARS-CoV-2受体7ACS、蛋白酶7AEH的对接即为金属配合物的分子对接实验。对合成化合物开展了计算机模拟（in silico）与体外分析。所有金属配合物均具有与小牛胸腺DNA（CT DNA）以插入模式结合的强倾向性。采用Gaussian 09W软件完成了优化几何构型与量子力学表征。合成化合物与SARS-CoV-2受体7ACS、蛋白酶7AEH的对接即为金属配合物的分子对接实验。对合成化合物开展了计算机模拟（in silico）与体外分析。