Coordination Behavior of Acylthiourea Ligands in Their Ru(II)–Benzene Complexes─Structures and Anticancer Activity
Coordination Behavior of Acylthiourea Ligands in Their Ru(II)–Benzene Complexes─Structures and Anticancer Activity
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酰基硫脲配体在钌(II)-苯配合物中的配位行为─结构和抗癌活性
DOI：
10.1021/acs.organomet.2c00127
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发表时间：
2022
期刊：
影响因子：
2.8
通讯作者：
R. Karvembu
中科院分区：
文献类型：
--
作者：
S. Swaminathan;J. Haribabu;M. M. Mohamed Subarkhan;G. Manonmani;K. Senthilkumar;Nithya Balakrishnan;N. Bhuvanesh;C. Echeverria;R. Karvembu
酰基硫脲配体在合成和应用化学中都有应用。配体的骨架包含几个杂原子，这些杂原子在其配合物中提供可变的配位模式。在这里，我们报告了这些类型的配合物在结晶时的一种不稳定行为。合成了6个含有酰基硫脲配体的Ru(II) -苯配合物（B1-B6），并利用分析和光谱技术对其进行了充分的表征。与光谱数据证实的配体与Ru（II）离子的单齿配位相反，在它们的Ru(II) -苯配合物的晶体结构中观察到双齿配位。据我们所知，这是目前唯一一篇关于Ru(II) -苯配合物中N， s配位酰基硫脲配体形成四元环的报道，而相同的配体在Ru(II) -对花香烃体系中表现为单齿配位。复合物（B1-B6）在A549中表现出良好的抗癌潜力，克服了cis549的顺铂耐药，但不幸的是对正常人脐静脉内皮细胞系表现出毒性。酰基硫脲配体c端链长度的增加和n端共轭似乎改善了配合物的细胞毒性谱。5-乙基-2 ' -脱氧尿苷染色有助于观察到活性复合物b4和b5对DNA合成的中断，并通过流式细胞术进一步验证，其中复合物在S期阻止了细胞周期。后者也证实了活性复合物诱导细胞死亡的凋亡模式，并通过吖啶橙/溴化乙啶染色显示了细胞凋亡引起的形态学变化。
Acylthiourea ligands have applications in both synthetic and applied chemistry. The skeleton of the ligand contains several heteroatoms which offer variable coordination modes in their complexes. Herein, we report one such erratic behavior of these types of complexes upon crystallization. Six Ru(II)–benzene complexes (B1–B6) containing the acylthiourea ligand were synthesized and adequately characterized using analytical and spectroscopic techniques. In contrast to the spectroscopic data confirming the monodentate coordination of the ligands to the Ru(II) ion, the bidentate version in the crystal structure of their Ru(II)–benzene complexes was observed. To the best of our knowledge, this is the only report as of now on N,S-coordinated acylthiourea ligands forming a four-membered ring in Ru(II)–benzene complexes, while the same ligands in the Ru(II)–p-cymene system showed a monodentate coordination. The complexes (B1–B6) exhibited good anticancer potential in A549, overcame cisplatin resistance in cisRA549, but unfortunately exhibited toxicity toward normal human umbilical vein endothelial cell lines. An increase in chain length at the C-terminal and the conjugation at the N-terminal of the acylthiourea ligands seemed to improve the cytotoxic profile of the complexes. 5-Ethynyl-2′-deoxyuridine staining helped to visualize the interruption of DNA synthesis by the active complexesB4andB5, which was further authenticated using flow cytometry, wherein the complexes arrested the cell cycle in the S phase. The latter also proved the apoptosis mode of cell death induced by the active complexes, and the morphological changes due to apoptosis were visualized using acridine orange/ethidium bromide staining.