Diiron Complexes with a Bridging Functionalized Allylidene Ligand: Synthesis, Structural Aspects, and Cytotoxicity

Regio- and stereoselective nucleophilic attack of cyanide (from NBu4CN) to cationic diiron vinyliminium compounds [Fe2Cp2(CO)­(μ-CO)­{μ-η1:η3-C­(R′)­C­(R″)­CNMe2}]­CF3SO3 ([1a–f]­CF3SO3) affords the nitrile-aminoallylidene derivatives 2a–f in good to excellent yield. The analogous reaction of [1g]­CF3SO3, comprising two different N substituents, gives 4 (63%) as a mixture of two stereoisomers. The new products [1g]­CF3SO3, 2a–f, and 4 were characterized by IR and NMR spectroscopy and in a number of cases by IR-spectroelectrochemistry and single-crystal X-ray diffraction. The allylidene complexes are air-stable and robust in aqueous solution; however, in general they undergo oxidation within a biologically relevant range of potentials. DFT calculations were carried out to rationalize the observed stereoselectivity of the synthesis reaction and other structural and thermodynamic aspects. The cytotoxicity of 2a–f was assessed on cisplatin-sensitive and -resistant human ovarian carcinoma (A2780 and A2780cisR) cell lines and human embryonic kidney (HEK-293) cells. Experiments reveal that treatment with the compounds leads to ROS production, with an absence of direct interactions with double-stranded DNA (calf thymus) and bovine serum albumin.氰离子（来自四丁基氰化铵NBu4CN）对阳离子型二铁乙烯亚胺鎓配合物[Fe2Cp2(CO)(μ-CO){μ-η1:η3-C(R′)C(R″)CNMe2}]CF3SO3（[1a–f]CF3SO3）发生区域与立体选择性的亲核进攻，以良好至优异的收率得到腈基氨基烯丙亚基衍生物2a–f。带有两种不同氮取代基的[1g]CF3SO3发生类似反应，以63%的收率得到两种立体异构体的混合物4。新型产物[1g]CF3SO3、2a–f及4经红外光谱（IR）、核磁共振波谱（NMR）表征，其中部分产物还通过红外光谱电化学与单晶X射线衍射完成了结构鉴定。该类烯丙亚基配合物在空气中稳定，且在水溶液中具有良好的稳定性；但总体而言，它们可在生物学相关的电势范围内发生氧化反应。本研究通过密度泛函理论（DFT）计算，对该合成反应中观察到的立体选择性以及其他结构与热力学性质进行了合理化阐释。针对2a–f的细胞毒性，研究分别在顺铂敏感型与顺铂耐药型人卵巢癌细胞系（A2780及A2780cisR）以及人胚肾（HEK-293）细胞中进行了评估。实验结果表明，该类化合物可诱导活性氧（ROS）生成，且不会与双链DNA（小牛胸腺DNA）及牛血清白蛋白发生直接相互作用。