一系列新的螯合双齿(SS)烷基咪唑-2-硫酮-Ru(II)/Os(II)配合物(3ai,3aii,3aiii,3bii/4aii,4bi,4bii),和三齿(SNS)吡啶-2,6-二基咪唑-2-硫酮-Ru(II)/Os(II)配合物(5bi,5civ/6bi,6ci,6civ)形式为[MII(cym)(L)Cl]PF6和[MII(cym)(L)]PF6(M=Ru或Os,Cym=η6-对异丙基苯,和L=硫脲的杂环衍生物),成功合成。光谱和分析方法用于表征配合物及其配体。固态单晶X射线衍射分析显示,在各个配合物中的Ru(II)或Os(II)中心周围呈“钢琴凳”几何形状。使用MTT测定法研究了复合物对人宫颈癌(HeLa)和非癌细胞系(Hek293)的体外化疗活性。化合物3aii,5civ,5bi,4aiii,6ci,6civ,和参考药物,发现5-氟尿嘧啶对肿瘤细胞具有选择性;化合物3ai,3aiii,3bii,4bi,4bii,6bi,发现在正常和肿瘤细胞系之间没有选择性。三齿半夹心复合物5bi的IC50值(86±9μM)显示出与参考的商业抗癌药物相当的抗增殖活性,5-氟尿嘧啶(87±15μM)。在各自的剂量浓度下,钳形(SNS)锇络合物6ci(36±10μM)和6civ(40±4μM)的有效性是参考药物5-氟尿嘧啶的两倍。然而,类似的夹式(SNS)钌络合物5civ是无效的,没有显示抗增殖活性,甚至在147±1μM的较高浓度下。这些发现暗示,络合物中的螯合(SS)和钳(SNS)配体结构的较高稳定性通过减少在生理条件下配体解离的机会来改善络合物的生物(抗增殖)活性。总的来说,夹式(SNS)锇配合物被发现比它们的钌类似物更具细胞毒性,表明咪唑-2-硫酮-Ru/Os配合物的抗增殖活性取决于配体的空间配位,金属中心的性质,和金属络合物离子的电荷。
A series of new chelating bidentate (SS) alkylimidazole-2-thione-Ru(II)/Os(II) complexes (3ai, 3aii, 3aiii, 3bii/4aiii, 4bi, 4bii), and the tridentate (SNS) pyridine-2,6-diylimidazole-2-thione-Ru(II)/Os(II) complexes (5bi, 5civ/6bi, 6ci, 6civ) in the forms [MII(cym)(L)Cl]PF6 and [MII(cym)(L)]PF6 (M = Ru or Os, cym = η6-p-cymene, and L = heterocyclic derivatives of thiourea) respectively, were successfully synthesized. Spectroscopic and analytical methods were used to characterize the complexes and their ligands. Solid-state single-crystal X-ray diffraction analyses revealed a \"piano-stool\" geometry around the Ru(II) or Os(II) centers in the respective complexes. The complexes were investigated for in vitro chemotherapeutic activities against human cervical carcinoma (HeLa) and the non-cancerous cell line (Hek293) using the MTT assay. The compounds 3aii, 5civ, 5bi, 4aiii, 6ci, 6civ, and the reference drug, 5-fluorouracil were found to be selective toward the tumor cells; the compounds 3ai, 3aiii, 3bii, 4bi, 4bii, and 6bi, which were found not to be selective between normal and tumor cell lines. The IC50 value of the tridentate half-sandwich complex 5bi (86 ± 9 μM) showed comparable anti-proliferative activity with the referenced commercial anti-cancer drug, 5-fluorouracil (87 ± 15 μM). The pincer (SNS)
osmium complexes 6ci (36 ± 10 μM) and 6civ (40 ± 4 μM) were twice as effective as the reference drug 5-fluorouracil at the respective dose concentrations. However, the analogous pincer (SNS) ruthenium complex 5civ was ineffective and did not show anti-proliferative activity, even at a higher concentration of 147 ± 1 μM. These findings imply that the higher stability of the chelating (SS) and the pincer (SNS) ligand architectures in the complexes improves the biological (anti-proliferative) activity of the complexes by reducing the chance of ligand dissociation under physiological conditions. In general, the pincer (SNS)
osmium complexes were found to be more cytotoxic than their ruthenium analogues, suggesting that the anti-proliferative activity of the imidazole-2-thione-Ru/Os complexes depends on the ligand\'s spatial coordination, the nature of the metal center, and the charge of the metal complex ions.