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首页> 外文期刊>Dalton transactions: An international journal of inorganic chemistry >Copper(ii) complex of methionine conjugated bis-pyrazole based ligand promotes dual pathway for DNA cleavage
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Copper(ii) complex of methionine conjugated bis-pyrazole based ligand promotes dual pathway for DNA cleavage

机译：蛋氨酸结合双吡唑基配体的铜（ii）配合物促进DNA切割的双重途径

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摘要

Three Cu~(II) complexes of bis-pyrazole based ligands have been synthesized and structurally characterized by X-ray crystallography. One of the ligand (L2) contains a methionine ester conjugated to a bis-pyrazole carboxylate through an amide linkage. The binding constant for complexes 1-3 with CT DNA are of the order of 10~4 M~(-1). The crystal structure suggests that the axial Cu-O bonds (ca. 2.31(4) ?) are relatively labile and hence during the redox cycle with ascorbic acid and oxygen one or both the axial Cu-O bonds might open to promote copper oxygen reaction and generate ROS. The chemical nuclease activity of complexes 1-3 in dark, show complete relaxation of supercoiled DNA at 100 μM concentration in presence of ascorbic acid (H_2A). The mechanistic investigation suggests that the complexes 1 and 2 show involvement of peroxo species whereas 3 shows involvement of both singlet oxygen and peroxo species in DNA cleavage. The singlet oxygen formation in dark is otherwise unfavourable but the presence of methionine as pendant arm in L2 might activate the generation of singlet oxygen from the metal generated peroxo species. The results of DNA cleavage studies suggest that methionine based copper(ii) complexes can promote dual pathway for DNA cleavage. Probing the cytotoxic activity of these complexes on MCF-7, human breast cancer cell line shows that 3 is the most effective one with an IC_(50) of 70(2) μM.
机译：合成了三种基于双吡唑的配体Cu〜（II）配合物，并通过X射线晶体学对其结构进行了表征。配体（L2）之一含有通过酰胺键与双吡唑羧酸酯共轭的蛋氨酸酯。 1-3与CT DNA的配合物的结合常数约为10〜4 M〜（-1）。晶体结构表明，轴向Cu-O键（约2.31（4）？）相对不稳定，因此在抗坏血酸和氧的氧化还原循环中，一个或两个轴向Cu-O键可能会打开以促进铜氧反应并产生ROS。在黑暗中，复合物1-3的化学核酸酶活性显示超螺旋DNA在抗坏血酸（H_2A）存在下完全松弛，浓度为100μM。机理研究表明，复合物1和2显示了过氧化物物种的参与，而复合物1和2显示了单重态氧和过氧化物物种都参与了DNA切割。否则在黑暗中形成单线态氧是不利的，但蛋氨酸作为L2中的侧链臂的存在可能会激活由金属生成的过氧物质生成单线态氧。 DNA裂解研究的结果表明，基于蛋氨酸的铜（ii）配合物可以促进DNA裂解的双重途径。探测这些复合物对MCF-7的细胞毒活性，人乳腺癌细胞系显示3是最有效的，IC_（50）为70（2）μM。

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