First- and Second-Generation Heterometallic Dendrimers Containing Ferrocenyl-Ruthenium(II)-Arene Motifs: Synthesis, Structure, Electrochemistry, and Preliminary Cell Proliferation Studies

Four first- and second-generation heterometal lic ferrocenyl derived p-cymene-Ru(II) metallodendrimers, of general formula [DAB-PPI{(eta(6)-p-cymene)Ru((C7H5NO)-kappa(2)-N,O)PTA(5-ferrocenylvinyl)}(n)[PF6](n), and [DAB-PPI{eta(6)-p-cymene)Ru((C6H5N2)-kappa(2)-N,N)Cl(5-ferrocenylvinyl)}(n)][PF6](n) (where n = 4 (G(1)), 8 (G(2)), DAB = 1,4-diaminobutane, PPI = poly(propyleneimine), PTA = 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane) have been synthesized. All complexes have been characterized using analytical (i.e., HR-ESI mass spectrometry, HPLC, elemental analysis, and cyclic voltammetry) and spectroscopic (i.e. H-1 and C-13{H-1} NMR and infrared) methods. Electrochemical studies reveal that the N,O-p-cymene-Ru(II)-PTA complexes result in two irreversible redox processes (oxidation of the Fe(II) and Ru(II) centers), while the N,N-p-cymene-Ru(II) complexes display one reversible wave (Fe(II)/Fe(III) couple). Heterometallic model complexes have been prepared, and for one of the complexes, its molecular structure has been determined by single-crystal X-ray crystallography. In vitro antiproliferation activity of the dendritic ligands and their complexes were evaluated against A2780 and A2780cisR human ovarian cancer lines, the SISO human cervix cancer line, the LCLC-103H human lung cancer line, and the 5637 human bladder cancer line. Nine of the twelve compounds slowed the growth of the ovarian cancer cell lines by more than 50% at equi-iron concentrations of 5 mu M.