Design, synthesis and characterization of new diiron organometallic complexes for biological use

Two series of novel diiron complexes of general formula [Fe2Cp2(CO)(µ-CO){µ-η1:η3- C3(R’’)C2HC1=NMe(R’)}][CF3SO3] (3a-f) and [Fe2{µ-η1:η3-C3(R’’)C2{N(Me)N=C4(H)(COOEt)-C1=N(R)(R’)}((Cp)2(CO)(µ-CO)][Y] (Y = NO3, 5a,b; Y = CF3SO3, 5c), were synthetized and characterized by elemental analysis, IR, 1H and 13C NMR spectroscopy; moreover, the X-ray structures of 3a (R’ = 4-C6H4OMe, R’’ = Cy), 3b (R’ = 4-C6H4OMe, R’’ = CH2Cy) and 3c (R’ = Cy, R’’ = 4-C6H4OMe) were ascertained by single-crystal X-ray diffraction studies. Compounds 3a-f, bearing different substituents on the bridging vinyliminium ligand, were obtained in 53-98% yields from the reactions of diiron µ-aminocarbyne precursorsbwith various alkynes. Compounds 5a-c were obtained in 53-67% yields from the reactions of diiron µ-vinyliminium precursors with N2CHCOOEt and NaOMe under inert atmosphere. NMR and UV–Vis methods were used to assess the D2O solubility, the stability in aqueous solution at 37 °C and the octanol–water partition coefficients of the complexes. A screening study evidenced a potent cytotoxicity of 3 and 5 against the CT26 and U87 cancer cell lines; complexes 3a, 3b, 3d (R’ = R’’ = Cy), 3e (R’ = Bn, R’’ = Cy) and 5b (R = R’ = Bn, R’’ = Ph) revealed the most performant of each series, respectively. Seahorse Mito Stress Test experiment was performed on a selection of compounds to evaluate the O2 consumption rate. These results are in accordance with the IC50 values. Dynamic Light Scattering experiment on the same selection of complexes revealed the formation of nanoparticles in filtered 10% FBS in PBS