Abstract

Multidentate copper metal complexes have been in the limelight in the area of DNA interaction studies exhibiting intercalation, groove binding and cross linking modes. Design of metal complex based on the versatile ligands decides their mode of DNA binding behavior. Based on this, a tetradentate Copper (II) complex, [Cu(L)(4,4’-bpy)], is synthesized using ONO hydrazone ligand and ancillary ligand, 4,4’-bipyridine. It is characterized by physico-chemical and UV-Visible, FTIR, Mass and EPR spectroscopic techniques. The binding pattern of the characterized complex with DNA has been assessed by UV absorption and fluorescence spectral titrations as well as viscosity studies and it has exhibited peculiar threading intercalation. The binding constant, K_b value of the synthesized complex was found to be (4.38 ± 0.09) × 10⁴ M⁻¹, greater than that of the hydrazone ligand (K_b = 2.29 × 10⁴ M⁻¹) and lesser than the classical intercalator ethidium bromide - EtBr (K_b = 10⁷). The fluorescence quenching assays in the presence of ethidium bromide and viscometric studies show threading intercalative mode of binding of the complex to the DNA base pairs. Molecular docking studies further supports such a binding pattern with the bipyridine ring of the complex intercalating with deoxycytosine nucleobase of DNA. ADME (Absorption, Distribution, Metabolism and Excretion) parameters of the complex and ligand were predicted to get an idea of drug likeliness and to correlate the structural properties with semi DNA intercalative pattern of the same.

摘要

多齿铜金属配合物在表现出嵌入、凹槽结合和交联模式的 DNA 相互作用研究领域一直备受关注。基于多功能配体的金属配合物设计决定了它们的 DNA 结合行为模式。基于此，使用 ONO 腙配体和辅助配体 4,4'-联吡啶合成了四齿铜 (II) 配合物 [Cu(L)(4,4'-bpy)]。它的特点是物理化学和紫外可见光、FTIR、质谱和 EPR 光谱技术。已通过紫外吸收和荧光光谱滴定以及粘度研究评估了表征复合物与 DNA 的结合模式，并表现出特殊的穿线嵌入。发现合成复合物的结合常数K _b值为(4.38 ± 0.09) × 10 ⁴ M ^{- 1}，大于腙配体 ( K _b = 2.29 × 10 ⁴ M ^-1 )，小于经典嵌入剂溴化乙锭 - EtBr ( K _b = 10 ⁷ )。在溴化乙锭存在下的荧光猝灭分析和粘度研究显示了复合物与 DNA 碱基对结合的穿插嵌入模式。分子对接研究进一步支持这种结合模式，复合物的联吡啶环嵌入 DNA 的脱氧胞嘧啶核碱基。ADME （吸收、分布、代谢和排泄） 预测复合物和配体的参数以获得药物可能性的概念，并将结构特性与相同的半 DNA 嵌入模式相关联。