The synthesis and biological assessment of neutral or cationic platinum group metal-based anticancer complexes have been extremely studied, whereas there are few reports on the corresponding zwitterionic complexes. Herein, the synthesis, characterization, and bioactivity of zwitterionic half-sandwich phosphine–imine iridium(III), rhodium(III), and ruthenium(II) complexes were presented. The sulfonated phosphine–imine ligand and a group of zwitterionic half-sandwich P,N-chelating organometallic complexes were fully characterized by nuclear magnetic resonance (NMR), mass spectrum (electrospray ionization, ESI), elemental analysis, and X-ray crystallography. The solution stability of these complexes and their spectral properties were also determined. Notably, almost all of these complexes showed enhanced anticancer activity against model HeLa and A549 cancer cells than the corresponding zwitterionic pyridyl–imine N,N-chelating iridium(III) and ruthenium(II) complexes, which have exhibited inactive or low active in our previous work. The increase in the lipophilic property and intracellular uptake levels of these zwitterionic P,N-chelating complexes appeared to be associated with their superior cytotoxicity. In addition, these complexes showed biomolecular interactions with bovine serum albumin (BSA). The flow cytometry studies indicated that the representative complex Ir1 could induce early-stage apoptosis in A549 cells. Further, confocal microscopy imaging analysis displayed that Ir1 entered A549 cells through the energy-dependent pathway, targeted lysosome, and could cause lysosomal damage. In particular, these complexes could impede cell migration in A549 cells.

中文翻译：

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在两性离子半夹心铱 (III)、铑 (III) 和钌 (II) 配合物中增加膦连接的抗癌活性

中性或阳离子铂族金属基抗癌配合物的合成和生物学评价已被大量研究，而相应的两性离子配合物的报道很少。在此，介绍了两性离子半夹心膦-亚胺铱 (III)、铑 (III) 和钌 (II) 配合物的合成、表征和生物活性。磺化膦亚胺配体和一组两性离子半夹心P , N-螯合有机金属配合物通过核磁共振 (NMR)、质谱（电喷雾电离、ESI）、元素分析和 X 射线晶体学进行了全面表征。还确定了这些配合物的溶液稳定性及其光谱特性。值得注意的是，与相应的两性离子吡啶基亚胺N、N-螯合铱 (III) 和钌 (II) 配合物相比，几乎所有这些配合物都显示出对模型 HeLa 和 A549 癌细胞的抗癌活性增强，后者在我们的研究中表现出无活性或低活性之前的工作。这些两性离子P、N的亲脂性和细胞内摄取水平的增加-螯合复合物似乎与其优异的细胞毒性有关。此外，这些复合物显示出与牛血清白蛋白 (BSA) 的生物分子相互作用。流式细胞术研究表明，代表性复合物Ir1可诱导 A549 细胞发生早期凋亡。此外，共聚焦显微镜成像分析显示Ir1通过能量依赖性途径进入 A549 细胞，靶向溶酶体，并可能引起溶酶体损伤。特别是，这些复合物可以阻碍 A549 细胞中的细胞迁移。