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

• Published in: Dalton transactions : an international journal of inorganic chemistry 2012-01, Vol.41 (2), p.432-441
• Main Authors: Nieto, Daniel, González-Vadillo, Ana M, Bruña, Sonia, Pastor, César J, Ríos-Luci, Carla, León, Leticia G, Padrón, José M, Navarro-Ranninger, Carmen, Cuadrado, Isabel
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cell Culture Techniques; Cell Cycle - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Crystallography, X-Ray; Electrochemistry; Ferrous Compounds - chemical synthesis; Ferrous Compounds - chemistry; Humans; Models, Molecular; Molecular Conformation; Organoplatinum Compounds - chemical synthesis; Organoplatinum Compounds - chemistry; Organoplatinum Compounds - pharmacology
• ISSN: 1477-9226; 1477-9234
• DOI: 10.1039/c1dt11358e

A new family of heterometallic compounds 3-6 containing ferrocenyl and platinum(II) centers has been synthesized by reaction of 1-β-aminoethylferrocene (1) and 1,1'-bis(β-aminoethyl)ferrocene (2) with Pt(II) precursors. Using K(2)[PtCl(4)] as the Pt(II) source, the cis-square-planar neutral compounds [Fe{η(5)-C(5)H(4)(CH(2))(2)NH(2)}(2)PtCl(2)] (3) and [{Fe(η(5)-C(5)H(4)(CH(2))(2)NH(2))(η(5)-C(5)H(5))}(2)PtCl(2)] (5) were obtained. Reaction of cis-[PtCl(2)(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{η(5)-C(5)H(4)(CH(2))(2)NH(2)}(2)Pt(dmso)Cl]Cl (4) and [Fe(η(5)-C(5)H(4)(CH(2))(2)NH(2))(η(5)-C(5)H(5))Pt(dmso)Cl(2)] (6). Compounds 3-6 were thoroughly characterized using multinuclear ((1)H, (13)C, (195)Pt) 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 μM. 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.