N-Heterocyclic carbene (NHC) ligands are widely investigated in medicinal inorganic chemistry. Here, we report the preparation and characterization of a series of half-sandwich [M(L)(NHC)Cl₂] (M = Ru, Os, Rh, Ir; L = cym/Cp*) complexes with a N-flanking anthracenyl moiety attached to imidazole- and benzimidazole-derived NHC ligands. The anticancer activity of the complexes was investigated in cell culture studies where, in comparison to a Rh derivative with an all-carbon-donor-atom-based ligand (5a), they were found to be cytotoxic with IC₅₀ values in the low micromolar range. The Ru derivative 1a was chosen as a representative for stability studies as well as for biomolecule interaction experiments. It underwent partial chlorido/aqua ligand exchange in DMSO-d₆/D₂O to rapidly form an equilibrium in aqueous media. The reactions of 1a with biomolecules proceeded quickly and resulted in the formation of adducts with amino acids, DNA, and protein. Hen egg white lysozyme crystals were soaked with 1a, and the crystallographic analysis revealed an interaction with an l-aspartic acid residue (Asp119), resulting in the cleavage of the p-cymene ligand but the retention of the NHC moiety. Cell morphology studies for the Rh analog 3a suggested that the cytotoxicity is exerted via mechanisms different from that of cisplatin.

中文翻译：

---

半夹心卡宾配合物的蒽基官能化：体外抗癌活性和与生物分子的反应

N-杂环卡宾 (NHC) 配体在药物无机化学中得到广泛研究。在这里，我们报告了一系列半夹心 [M(L)(NHC)Cl ₂ ] (M = Ru、Os、Rh、Ir；L = cym/Cp*) 配合物的制备和表征，具有 N 侧翼蒽基部分连接到咪唑和苯并咪唑衍生的 NHC 配体。在细胞培养研究中研究了复合物的抗癌活性，与具有全碳供体原子基配体 ( 5a )的 Rh 衍生物相比，发现它们具有细胞毒性，IC ₅₀值在低微摩尔范围。Ru衍生物1a被选为稳定性研究和生物分子相互作用实验的代表。它在 DMSO- d ₆ /D ₂ O 中进行部分氯化物/水配体交换，以在水性介质中快速形成平衡。1a与生物分子的反应进行得很快，导致与氨基酸、DNA 和蛋白质形成加合物。鸡蛋清溶菌酶晶体用1a浸泡，晶体学分析显示与l-天冬氨酸残基 (Asp119)相互作用，导致p-伞花烃配体裂解，但保留了 NHC 部分。Rh 类似物3a 的细胞形态研究 表明细胞毒性是通过与顺铂不同的机制发挥的。