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两种新型混合配体铜(II)配合物与 DNA 的相互作用研究:热力学和光谱学研究。

Interaction of two new mixed ligand copper(II) complexes with DNA probed by thermodynamic and spectroscopic studies.

机构信息

Faculty of Chemistry, Sensor and Biosensor Research Center (SBRC) & Nanoscience and Nanotechnology Research Center (NNRC), Razi University, 67149, Kermanshah, Iran,

出版信息

Mol Biol Rep. 2014 Jan;41(1):25-37. doi: 10.1007/s11033-013-2828-4. Epub 2013 Nov 20.

DOI:10.1007/s11033-013-2828-4
PMID:24253899
Abstract

The DNA binding behavior of [Cu(4,7-dmp)(phen-dione)Cl]Cl (1) and [Cu(2,9-dmp)(phen-dione)Cl]Cl (2) where dmp and phen-dion stand for dimethyl-1,10-phenanthroline and 1,10-phenanthroline-5,6-dion, respectively, was studied with a series of techniques including Viscometry, UV-Vis absorption, circular dichroism and fluorescence spectroscopy. Cytotoxicity effect was also investigated. Thermodynamic parameters, enthalpy and entropy changes were calculated according to Van't Hoff equation, which indicated that both reactions are predominantly enthalpically driven. However, these two complexes show different behavior in fluorescence, circular dichroism and viscometry methods which indicate the Cu(II) complexes interact with calf-thymus DNA by different mode of binding. These have further been verified by competition studies using Hoechst as a distinct groove binder. All these results indicate that these two complexes (1) and (2) interact with CT-DNA via groove binding and partially intercalative mode, respectively and the binding affinity of the complex 1 is higher than that of complex 2. Finally, our findings suggest that the type of ligands and structure of complexes have marked effect on the binding affinity of complexes involving CT-DNA. Also, these new complexes showed excellent antitumor activity against human T lymphocyte carcinoma-Jurkat cell line.

摘要

[Cu(4,7-dmp)(phen-dione)Cl]Cl(1)和[Cu(2,9-dmp)(phen-dione)Cl]Cl(2)中[Cu(4,7-dmp)(phen-dione)Cl]Cl(1)和[Cu(2,9-dmp)(phen-dione)Cl]Cl(2)中[Cu(4,7-dmp)(phen-dione)Cl]Cl(1)和[Cu(2,9-dmp)(phen-dione)Cl]Cl(2)的 DNA 结合行为分别用一系列技术进行了研究,包括粘度法、紫外可见吸收光谱法、圆二色光谱法和荧光光谱法。还研究了细胞毒性作用。根据范特霍夫方程计算了热力学参数焓变和熵变,结果表明两个反应主要是焓驱动的。然而,这两个配合物在荧光、圆二色和粘度法中表现出不同的行为,这表明 Cu(II)配合物与小牛胸腺 DNA 以不同的结合模式相互作用。这进一步通过使用 Hoechst 作为独特的沟结合物的竞争研究得到了验证。所有这些结果表明,这两个配合物(1)和(2)分别通过沟结合和部分嵌入模式与 CT-DNA 相互作用,配合物 1 的结合亲和力高于配合物 2。最后,我们的研究结果表明,配体的类型和配合物的结构对涉及 CT-DNA 的配合物的结合亲和力有显著影响。此外,这些新配合物对人 T 淋巴细胞白血病-Jurkat 细胞系显示出优异的抗肿瘤活性。

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