Heterometallic platinum(II) compounds with β-aminoethylferrocenes: synthesis, electrochemical behaviour and anticancer activity

A new family of heterometallic compounds 3-6 containing ferrocenyl and platinum(II) centers has been synthesized by reaction of 1-beta-aminoethylferrocene (1) and 1,1'-bis(beta-aminoethyl)ferrocene (2) with Pt(II) precursors. Using K-2[PtCl4] as the Pt(II) source, the cis-square-planar neutral compounds [Fe{eta(5)-C5H4(CH2)(2)NH2}(2)PtCl2] (3) and [{Fe(eta(5)-C5H4(CH2)(2)NH2)(eta(5)-C5H5)}(2)PtCl2] (5) were obtained. Reaction of cis-[PtCl2(dmso)(2)] with 1 and 2 resulted in the displacement of dmso and chloride ligands from the platinum coordination sphere, affording the cationic and neutral compounds [Fe{eta(5)-C5H4(CH2)(2)NH2}(2)Pt(dmso)Cl]Cl (4) and [Fe(eta(5)-C5H4(CH2)(2)NH2)(eta(5)-C5H5)Pt(dmso)Cl-2] (6). Compounds 3-6 were thoroughly characterized using multinuclear (H-1, C-13, Pt-195) NMR, IR spectroscopy, ESI mass spectrometry and elemental analysis. Single-crystal X-ray analysis of heterometallic 6 confirmed the cis geometry of the molecule and revealed that the platinum atom is held in a perfect square-planar geometry. The electrochemical behaviour of the heterometallic compounds 3-6, which has been examined by cyclic (CV) and square wave (SWV) voltammetries in dichloromethane and dmso solution, is characterized by the reversible one-electron oxidation of the ferrocene moieties. The results of the biological activity studies revealed that the organometallic complex 5 is active against all cell lines with GI(50) values in the range 1.7-2.3 mu M. When compared to the standard anticancer drug cisplatin, heterotrimetallic 5, possessing two aminoethylferrocenyl units coordinated to the Pt(II) center, showed a greater activity profile in the colon cancer cell line. Cell cycle studies revealed that the new mixed compound exhibits a mechanism of action different to cisplatin.