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新型[Ru(5,6-dmp/3,4,7,8-tmp)₂(diimine)]²⁺ 配合物:非共价 DNA 和蛋白质结合、抗癌活性以及用于核和蛋白质成分的荧光探针。

New [Ru(5,6-dmp/3,4,7,8-tmp)₂(diimine)]²⁺ complexes: non-covalent DNA and protein binding, anticancer activity and fluorescent probes for nuclear and protein components.

机构信息

School of Chemistry, Bharathidasan University, Tiruchirapalli 620 024, India.

出版信息

J Inorg Biochem. 2012 Nov;116:151-62. doi: 10.1016/j.jinorgbio.2012.06.005. Epub 2012 Jun 18.

Abstract

A series of Ru(II) complexes of the type Ru(5,6-dmp)(2)(diimine)1-3 and Ru(tmp)(2)(diimine)4-6, where 5,6-dmp is 5,6-dimethyl-1,10-phenanthroline, tmp is 3,4,7,8-tetramethyl-1,10-phenanthroline and diimine is dipyrido-[3,2-d:2',3'-f]-quinoxaline (dpq), dipyrido[3,2-a:2',3'-c]phenazine (dppz) and 11,12-dimethyl-dipyrido[3,2-a:2',3'-c]phenazine (11,12-dmdppz), has been isolated and the DNA binding mode of the complexes studied by using emission and circular dichroic (CD) spectral techniques. All the complexes exhibit induced circular dichroism upon binding to calf thymus (CT) DNA and show preferential binding to AT and mixed (d(CGCGATCGCG)(2)) sequences rather than to GC sequences. The complex Ru(tmp)(2)(dpq)4 exhibits enhancement in luminescence higher than Ru(5,6-dmp)(2)(dpq)1 upon binding to DNA. In contrast, Ru(5,6-dmp)(2)(dppz)2 and Ru(5,6-dmp)(2)(dmdppz)3 exhibit luminescence enhancement higher than Ru(tmp)(2)(dppz)5 and Ru(tmp)(2)(dmdppz)6 respectively upon DNA binding, illustrating the importance of hydrophobic forces of interaction in determining the DNA binding affinity. Among the complexes, 4 exhibits the highest enhancement in fluorescence intensity upon binding to the protein bovine serum albumin (BSA). The cytotoxicity of the complexes has been studied by screening them against non-small lung carcinoma (NCI-H460) cell line. It is noteworthy that the complex showing the strongest DNA binding affinity exhibits the highest cytotoxicity. The efficiency of the complexes as fluorescent probes for detection of nuclear morphology and proteins has been evaluated by using fluorescence microscopy. Remarkably, 4, which shows strong hydrophobic forces of interaction when bound to DNA and protein, acts as fluorescent probes for detection of nuclear components in the head, and proteins in the tail, of sperms.

摘要

已经分离出一系列 Ru(II) 配合物,类型为 [Ru(5,6-dmp)(2)(二亚胺)]2+1-3 和 [Ru(tmp)(2)(二亚胺)]2+4-6,其中 5,6-dmp 是 5,6-二甲基-1,10-菲咯啉,tmp 是 3,4,7,8-四甲基-1,10-菲咯啉,二亚胺是二吡啶并[3,2-d:2',3'-f]-喹喔啉(dpq)、二吡啶并[3,2-a:2',3'-c]吩嗪(dppz)和 11,12-二甲基-二吡啶并[3,2-a:2',3'-c]吩嗪(11,12-dmdppz),并研究了这些配合物与小牛胸腺 DNA 的结合模式,使用发射和圆二色性 (CD) 光谱技术。所有配合物与小牛胸腺 (CT) DNA 结合时均表现出诱导圆二色性,并表现出对 AT 和混合 (d(CGCGATCGCG)(2)) 序列的优先结合,而不是对 GC 序列的结合。配合物 Ru(tmp)(2)(dpq)4 在与 DNA 结合时表现出高于 Ru(5,6-dmp)(2)(dpq)1 的发光增强。相比之下,Ru(5,6-dmp)(2)(dppz)2 和 Ru(5,6-dmp)(2)(dmdppz)3 在与 DNA 结合时表现出高于 Ru(tmp)(2)(dppz)5 和 Ru(tmp)(2)(dmdppz)6 的发光增强,这表明相互作用的疏水力在确定 DNA 结合亲和力方面的重要性。在这些配合物中,4 在与蛋白质牛血清白蛋白 (BSA) 结合时表现出最高的荧光强度增强。通过筛选非小细胞肺癌 (NCI-H460) 细胞系,研究了配合物的细胞毒性。值得注意的是,表现出最强 DNA 结合亲和力的配合物表现出最高的细胞毒性。通过荧光显微镜评估了配合物作为检测核形态和蛋白质的荧光探针的效率。值得注意的是,4 在与 DNA 和蛋白质结合时表现出强烈的疏水力,可作为检测精子头部核成分和尾部蛋白质的荧光探针。

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