MTA-SZTE Lendület Functional Metal Complexes Research Group, Department of Molecular and Analytical Chemistry, Interdisciplinary Excellence Centre, University of Szeged, Dóm tér 7-8., H-6720 Szeged, Hungary.
Department of Molecular and Analytical Chemistry, University of Szeged, Dóm tér 7-8., H-6720 Szeged, Hungary.
Dalton Trans. 2024 Mar 12;53(11):4984-5000. doi: 10.1039/d3dt04138g.
In this study, we present the synthesis, characterization and cytotoxicity of six organometallic [Ru(II)(η--cymene)(,)Cl]Cl, [Rh(III)(η-CMe)(,)Cl]Cl and [Re(I)(CO)(,)Cl] complexes, in which the (,) ligands are sterane-based 2,2'-bipyridine derivatives (4-Me-bpy-St-OH, 4-Ph-bpy-St-OH). The solution chemical behavior of the ligands and the complexes was explored by UV-visible spectrophotometry and H NMR spectroscopy. The ligands and their Re(I) complexes are neutral at pH = 7.40; this contributes to their highly lipophilic character (log > +3). The Ru(II) and Rh(III) half-sandwich complexes are much more hydrophilic, and this property is greatly affected by the actual chloride ion content of the medium. The half-sandwich Ru and Rh complexes are highly stable in 30% (v/v) DMSO/water (<5% dissociation at pH = 7.40); this is further increased in water. The Rh(III)(η-CMe) complexes were characterized by higher water/chloride exchange and p constants compared to their Ru(II)(η--cymene) counterparts. The Re(I)(CO) complexes are also stable in solution over a wide pH range (2-12) without the release of the bidentate ligand; only the chlorido co-ligand can be replaced with OH at higher pH values. A comprehensive discussion of the binding affinity of the half-sandwich Ru(II) and Rh(III) complexes toward human serum albumin and calf-thymus DNA is also provided. The Ru(II)(η--cymene) complexes interact with human serum albumin intermolecular forces, while for the Rh(III)(η-CMe) complexes the coordinative binding mode is suggested as well. They are also able to interact with calf-thymus DNA, most likely the coordination of the guanine nitrogen. The Ru(II)(η--cymene) complexes were found to be the most promising among the tested compounds as they exhibited moderate-to-strong cytotoxic activity (IC = 3-11 μM) in LNCaP as well as in PC3 prostate cells in an androgen receptor-independent manner. They were also significantly cytotoxic in breast and colon adenocarcinoma cancer cell lines and showed good selectivity for cancer cells.
在这项研究中，我们合成、表征并测试了六种有机金属[Ru(II)(η--Cymene)(,)Cl]Cl、[Rh(III)(η-CMe)(,)Cl]Cl 和 [Re(I)(CO)(,)Cl] 配合物的细胞毒性，其中（,)配体是基于甾烷的 2,2'-联吡啶衍生物（4-Me-bpy-St-OH、4-Ph-bpy-St-OH）。通过紫外可见分光光度法和 H NMR 光谱研究了配体和配合物的溶液化学行为。在 pH = 7.40 时，配体及其 Re(I)配合物呈中性；这使得它们具有高度的亲脂性（log > +3）。Ru(II)和 Rh(III)半夹心配合物的亲水性要强得多，而这种性质受介质中实际氯离子含量的影响很大。在 30%（v/v）DMSO/水中，Ru 和 Rh 半夹心配合物非常稳定（pH = 7.40 时<5%解离）；在水中进一步增加。与 Ru(II)(η--Cymene) 配合物相比，Rh(III)(η-CMe)配合物具有更高的水/氯离子交换和 p 常数。在很宽的 pH 范围（2-12）内，Re(I)(CO)配合物在溶液中也很稳定，不会释放出双齿配体；只有在较高 pH 值下，氯代配位体才能被 OH 取代。还全面讨论了 Ru(II)和 Rh(III)半夹心配合物与人血清白蛋白和小牛胸腺 DNA 的结合亲和力。Ru(II)(η--Cymene)配合物与人血清白蛋白相互作用主要是分子间力，而对于 Rh(III)(η-CMe)配合物，则建议采用配位键合模式。它们也能够与小牛胸腺 DNA 相互作用，最有可能是与鸟嘌呤氮配位。在测试的化合物中，Ru(II)(η--Cymene)配合物最有前途，因为它们以雄激素受体非依赖性方式在 LNCaP 以及 PC3 前列腺细胞中表现出中等至强的细胞毒性（IC = 3-11 μM）。它们在乳腺癌和结肠癌腺癌癌细胞系中也具有显著的细胞毒性，并对癌细胞表现出良好的选择性。
