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

Abstract

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 K₂[PtCl₄] as the Pt(II) source, the cis-square-planar neutral compounds [Fe{η⁵-C₅H₄(CH₂)₂NH₂}₂PtCl₂] (3) and [{Fe(η⁵-C₅H₄(CH₂)₂NH₂)(η⁵-C₅H₅)}₂PtCl₂] (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{η⁵-C₅H₄(CH₂)₂NH₂}₂Pt(dmso)Cl]Cl (4) and [Fe(η⁵-C₅H₄(CH₂)₂NH₂)(η⁵-C₅H₅)Pt(dmso)Cl₂] (6). Compounds 3–6 were thoroughly characterized using multinuclear (¹H, ¹³C, ¹⁹⁵Pt) 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 GI₅₀ 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.