Gorlaeus Laboratories, Leiden Institute of Chemistry, Leiden University, P.O. Box 9502, 2300 RA, Leiden, The Netherlands.
J Biol Inorg Chem. 2014 Jun;19(4-5):675-89. doi: 10.1007/s00775-013-1083-4. Epub 2014 Jan 16.
Synthesis, spectroscopy, characterization, structures, and cytotoxicity studies of 2,6-bis(2,6-diisopropylphenyliminomethyl)pyridine (LLL) ruthenium compounds are described. The starting compound [RuCl3(LLL)] has been fully characterized using IR spectroscopy, UV-vis spectroscopy, electrospray ionization mass spectrometry, and NMR spectroscopy. In addition, the crystal structure of the ligand LLL has been determined using single-crystal X-ray diffraction. With the ruthenium(III) trichloride compound as starting material, a new family of Ru(II) complexes with a number of neutral and charged bidentate co-ligands have been synthesized and used for characterization and cytotoxicity studies. The synthesis of the corresponding Ru(II)LLL(LL)Cl complexes with co-ligands- LL is 1,10-phenanthroline, 2,2'-bipyridyl, 2-(phenylazo)pyridine, 2-(phenylazo)-3-methylpyridine, 2-(tolylazo)pyridine, or the anionic 2-picolinate-is reported. Analytical, spectroscopic (IR spectroscopy, UV-vis spectroscopy, (1)H NMR spectroscopy, and electrospray ionization mass spectrometry), and structural characterization of the new compounds is described. Crystal structure analyses of two Ru(II) compounds show a slightly distorted octahedral Ru(II) geometry with tridentate LLL coordinated in a planar meridional fashion, and the chelating co-ligand (LL) and a chloride ion complete the octahedron. The co-ligand plays a significant role in modulating the physicochemical and cytotoxic properties of these new ruthenium complexes. The in vitro cytotoxicity of these new Ru(II) complexes (half-maximal inhibitory concentration, IC50, of 0.5-1.5 μM), in comparison with the parent Ru(III) compound (half-maximal inhibitory concentration of 3.9-4.3 μM) is higher for several of the human cancer cell lines tested. The cytotoxic activity of some of the new ruthenium compounds is even higher than that of cisplatin in the same cancer cell lines. The cytotoxicity of these new anticancer compounds is discussed in the light of structure-based activity relationships, and a possible mechanism of action is suggested.
2,6-双(2,6-二异丙基苯亚氨基甲基)吡啶（LLL）钌化合物的合成、光谱学、表征、结构和细胞毒性研究
介绍了 2,6-双(2,6-二异丙基苯亚氨基甲基)吡啶（LLL）钌化合物的合成、光谱学、表征、结构和细胞毒性研究。起始化合物[RuCl3(LLL)]已通过红外光谱、紫外可见光谱、电喷雾电离质谱和 NMR 光谱进行了充分表征。此外，配体 LLL 的晶体结构已通过单晶 X 射线衍射确定。以三氯化钌(III)化合物为起始原料，合成了一系列具有中性和带电荷双齿共配体的新型 Ru(II)配合物，并对其进行了表征和细胞毒性研究。相应的Ru(II)LLL(LL)Cl配合物的合成，其中 LL 是 1,10-菲咯啉、2,2'-联吡啶、2-(苯偶氮)吡啶、2-(苯偶氮)-3-甲基吡啶、2-(甲苯偶氮)吡啶或阴离子 2-吡啶甲酸，已被报道。新化合物的分析、光谱学（红外光谱、紫外可见光谱、（1）H NMR 光谱和电喷雾电离质谱）和结构表征均已完成。对两个 Ru(II)化合物的晶体结构分析表明，Ru(II)的几何形状略有扭曲，为八面体，三齿 LLL 以平面轴向方式配位，螯合共配体（LL）和一个氯离子完成八面体。共配体在调节这些新的钌配合物的物理化学和细胞毒性性质方面起着重要作用。与母体 Ru(III)化合物（半数最大抑制浓度（IC50）为 3.9-4.3 μM）相比，这些新的 Ru(II)配合物（半数最大抑制浓度（IC50）为 0.5-1.5 μM）对测试的几种人类癌细胞系具有更高的体外细胞毒性。一些新的钌化合物的细胞毒性甚至高于同一癌细胞系中的顺铂。根据结构活性关系讨论了这些新的抗癌化合物的细胞毒性，并提出了一种可能的作用机制。
