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Comparative solution equilibrium and structural studies of half-sandwich ruthenium(II)(η6-toluene) complexes of picolinate derivatives
Journal of Inorganic Biochemistry ( IF 3.9 ) Pub Date : 2018-01-06 , DOI: 10.1016/j.jinorgbio.2017.12.017
Jelena M. Poljarević , G. Tamás Gál , Nóra V. May , Gabriella Spengler , Orsolya Dömötör , Aleksandar R. Savić , Sanja Grgurić-Šipka , Éva A. Enyedy

Five Ru(II)(η6-toluene) complexes formed with 2-picolinic acid and its various derivatives have been synthesized and characterized. X-ray structures of four complexes are also reported. Complex formation processes of [Ru(II)(η6-toluene)(H2O)3]2+ organometallic cation with the metal-free ligands were studied in aqueous solution in the presence of chloride ions by the combined use of 1H NMR spectroscopy, UV–visible spectrophotometry and pH-potentiometry. Solution stability, chloride ion affinity and lipophilicity of the complexes were characterized together with in vitro cytotoxic and antiproliferative activity in cancer cell lines being sensitive and resistant to classic chemotherapy and in normal cells as well. Formation of mono complexes such as [Ru(η6-toluene)(L)(Z)]+/0 (L: completely deprotonated ligand; Z = H2O/Cl) with high stability and [Ru(η6-toluene)(L)(OH)] was found in solution. The pKa values (8.3–8.7) reflect the formation of low amount of mixed hydroxido species at pH 7.4 at 0.2 M KCl ionic strength. The complexes are fairly hydrophilic and show moderate chloride ion affinity and fast chloride-water exchange processes. The studied complexes exhibit no cytotoxic activity in human cancer cells (IC50 > 100 μM), only complexes formed with 2-picolinic acid (1) and its 3-methyl derivative (2) represented a moderate antiproliferative effect (IC50 = 84.8 (1), 79.2 μM (2)) on a multidrug resistant colon adenocarcinoma cell line revealing considerable multidrug resistant selectivity. Complexes 1 and 2 bind to human serum albumin covalently and relatively slowly with moderate strength at multiple binding sites without ligand cleavage.



中文翻译:

比较溶液平衡和半夹心钌的结构研究(II)(η 6 -甲苯)络合物吡啶甲酸衍生物的

五个的Ru(II)(η 6 -甲苯)络合物与2-皮考啉酸及其各种衍生物已被合成和表征形成。还报道了四种配合物的X射线结构。的[Ru(II)(η的复合物形成的过程6 -甲苯)(H 2 O)3 ] 2+的有机金属与无金属阳离子的配体在氯离子存在下水溶液通过组合使用进行了研究1个ħ NMR光谱,紫外可见分光光度法和pH电位计。结合体外对溶液的稳定性,氯离子亲和力和亲脂性进行了表征在癌细胞系中对经典化学疗法敏感且具有抗性的细胞毒和抗增殖活性以及在正常细胞中也是如此。单声道的形成配合物如[茹(η 6 -甲苯)(L)(Z)] + / 0(L:完全去质子化的配位体; Z = H 2 O /氯- )具有高稳定性和的[Ru(η 6 -溶液中发现有甲苯)(L)(OH)]。p K a值(8.3–8.7)反映了在pH 7.4和0.2 M KCl离子强度下少量混合羟基物种的形成。该配合物是相当亲水的,并且显示出适度的氯离子亲和力和快速的氯-水交换过程。所研究的复合物在人类癌细胞中没有细胞毒性活性(IC 50 > 100μM),只有与2-吡啶甲酸(1)及其3-甲基衍生物(2)形成的复合物对多药耐药结肠具有中等的抗增殖作用(IC 50  = 84.8(1),79.2μM(2))。腺癌细胞系显示出显着的多药耐药性。配合物12在多个结合位点以中等强度共价且相对缓慢地与人血清白蛋白结合,而没有配体裂解。

更新日期:2018-01-06
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