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发光抗癌钌(II)-芳烃联吡啶和菲咯啉配合物:合成、表征、密度泛函理论研究、生物相互作用及细胞成像应用

Luminescent anticancer Ru(II)-arenebipyridine and phenanthroline complexes: Synthesis, characterization, DFT studies, biological interactions and cellular imaging application.

作者信息

P K Anuja, Paira Priyankar

机构信息

Department of Chemistry, School of Advanced Sciences, Vellore Institute of Technology, Vellore 632014, Tamilnadu, India.

Department of Chemistry, School of Advanced Sciences, Vellore Institute of Technology, Vellore 632014, Tamilnadu, India.

出版信息

J Inorg Biochem. 2020 Jul;208:111099. doi: 10.1016/j.jinorgbio.2020.111099. Epub 2020 May 16.

DOI:10.1016/j.jinorgbio.2020.111099
PMID:32460056
Abstract

A series of ruthenium(II)-arene complexes of several bipyridine and phenanthroline derivatives have been synthesized by employing a green and efficient protocol involving water as a solvent under sonication. The structures of all the complexes were elucidated by the spectroscopic analysis. The geometry of the chlorido and PTA (1,3,5-Triaza-7-phosphaadamantane) complexes were further confirmed by DFT and single crystal XRD. The stability study in various solvents, specifically in the intracellular one was conducted. Most of the compounds exhibited significant potency and selectivity against MCF7 and HeLa cell lines with respect to normal HEK-293 cells compared to cisplatin and RAPTA-C (Ruthenium(II)-arene PTA complex). Complex [(η6-hexamethylbenzene)RuCl(κ2-N,N-4,4'-di-n-nonyl-2,2'-bpy)]Cl (3e) presented best anticancer profiles against all the human cancer cells. Interestingly, few complexes turned up to be highly fluorescent depicted by the quantum yield values. Remarkably, [(η6-p-cymene)RuCl(κ2-N,N-bpy)]Cl (3i) was identified as most significant anticancer theranostic agent interms of potency, selectivity and fluorescence quantum yield. This complex also represented itself as significant cellular imaging agent in live U-87 MG cells which was monitored by confocal microscope. Absorption and emission spectral studies of bypyridine and phenanthroline complex series revealed that the complexes interacted with calf thymus DNA through groove binding as well as intercalative mode. In addition to this, strong binding efficacy of these scaffolds wih BSA (Bovin Serum Albumin) also enhanced their transportation property inside the cells.

摘要

通过采用一种绿色高效的方法,即在超声处理下以水为溶剂,合成了一系列含有几种联吡啶和菲咯啉衍生物的钌(II)-芳烃配合物。通过光谱分析阐明了所有配合物的结构。通过密度泛函理论(DFT)和单晶X射线衍射(XRD)进一步证实了氯和PTA(1,3,5-三氮杂-7-磷杂金刚烷)配合物的几何结构。进行了在各种溶剂中的稳定性研究,特别是在细胞内溶剂中的稳定性研究。与顺铂和RAPTA-C(钌(II)-芳烃PTA配合物)相比,大多数化合物对MCF7和HeLa细胞系相对于正常HEK-293细胞表现出显著的效力和选择性。配合物[(η6-六甲基苯)RuCl(κ2-N,N-4,4'-二正壬基-2,2'-联吡啶)]Cl(3e)对所有人类癌细胞表现出最佳的抗癌特性。有趣的是,通过量子产率值显示,少数配合物具有高荧光性。值得注意的是,[(η6-对异丙基苯)RuCl(κ2-N,N-联吡啶)]Cl(3i)在效力、选择性和荧光量子产率方面被确定为最显著的抗癌诊疗剂。该配合物在活的U-87 MG细胞中也表现为重要的细胞成像剂,通过共聚焦显微镜进行监测。对联吡啶和菲咯啉配合物系列的吸收和发射光谱研究表明,这些配合物通过沟槽结合以及插入模式与小牛胸腺DNA相互作用。除此之外,这些支架与牛血清白蛋白(BSA)的强结合效力也增强了它们在细胞内的运输特性。

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