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)(mu-CO){mu-eta(1):eta(3)-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 [lg]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.