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Synthesis, characterisation and DNA intercalation studies of regioisomers of ruthenium (II) polypyridyl complexes
Journal of Inorganic Biochemistry ( IF 3.9 ) Pub Date : 2018-02-09 , DOI: 10.1016/j.jinorgbio.2018.01.018
Laura Perdisatt , Samar Moqadasi , Luke O'Neill , Gary Hessman , Alessandra Ghion , Muhammad Qasim Mushtaq Warraich , Alan Casey , Christine O'Connor

Regioisomers of the functional group of the main ligand (L) on a series of [Ru(phen)2L]2+and [Ru(bpy)2L]2+ complexes, where phen is 1,10 phenanthroline and bpy is 2,2′-bipyridine, were synthesised to investigate the interaction with deoxyribonucleic acid (DNA) as potential therapeutics. UV–Vis binding titrations, thermal denaturation and circular dichroism were used to evaluate their interaction with DNA. The conclusions indicated the significance of the auxiliary ligand; especially 1,10-phenanthroline has on the binding constants (Kb). The systematic variation of auxiliary ligand(phen or bpy), and polypyridyl ligand (4-(1H-Imidazo[4,5-f][1,10]phenanthrolin-2-yl)benzonitrile (CPIP), 2-(4-formylphenyl)imidazo[4,5-f] [1,10] phenanthroline (FPIP), 2-(4-bromophenyl)imidazo[4,5-f][1,10]phenanthroline (BPIP) and 2-(4-nitrophenyl)imidazo[4,5-f] [1,10] phenanthroline (NPIP), split in terms of functional group change were investigated for DNA interaction. The CPIP analogues in particular were investigated for the regioisomerism (ortho, meta, para) effect of the nitrile group on the ligand. It was found that both the DNA interaction could be tailored through the systematic variation of the electronic nature of the individual auxiliary ligand and to a lesser extent the functional group and regioisomeric change. Preliminary cell line studies have been carried out to determine the selectivity of the complexes against cell lines such as A375 (Skin Cancer), HeLa (Cervical Cancer), A549 (Lung Cancer), Beas2B (Lung Normal Cell) and MCF-7 (Breast Cancer). Complexes which had strong DNA interactions in the binding studies have proven to be the most efficacious against certain cell lines. Establishing well-defined structure property relationships when looking at trends in spectroscopic properties and DNA binding will aid in the intelligent design of potential therapeutic complexes.



中文翻译:

钌(II)多吡啶基配合物区域异构体的合成,表征和DNA嵌入研究

一系列[Ru(phen)2 L] 2+和[Ru(bpy)2 L] 2+配合物上主要配体(L)的官能团的区域异构体,其中phen为1,10菲咯啉,bpy为2合成了2'-联吡啶,以研究与脱氧核糖核酸(DNA)的相互作用作为潜在的治疗方法。UV-Vis结合滴定,热变性和圆二色性用于评估它们与DNA的相互作用。结论表明了辅助配体的重要性。特别是1,10-菲咯啉对结合常数(K b)。辅助配体(phen或bpy)和聚吡啶基配体(4-(1H-咪唑并[4,5-f] [1,10]菲咯啉-2-基)苄腈(CPIP),2-(4-甲酰基苯基)咪唑并[4,5-f] [1,10]菲咯啉(FPIP),2-(4-溴苯基)咪唑并[4,5-f] [1,10]菲咯啉(BPIP)和2-(4-研究了硝基苯基)咪唑并[4,5-f] [1,10]菲咯啉(NPIP)在DNA相互作用方面的功能基团变化,特别是CPIP类似物的区域异构现象(邻位对位腈基对配体的影响。已经发现,可以通过各个辅助配体的电子性质的系统变化和较小程度的官能团和区域异构体变化来定制两种DNA相互作用。已经进行了初步的细胞系研究,以确定复合物对诸如A375(皮肤癌),HeLa(宫颈癌),A549(肺癌),Beas2B(肺正常细胞)和MCF-7(乳腺癌)等细胞系的选择性癌症)。在结合研究中具有强大的DNA相互作用的复合物已被证明对某些细胞系最有效。在查看光谱特性和DNA结合趋势时建立明确定义的结构特性关系将有助于潜在治疗复合物的智能设计。

更新日期:2018-02-09
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