Catalytically Generated Ferrocene-Containing Guanidines as Efficient Precursors for New Redox-Active Heterometallic Platinum(II) Complexes with Anticancer Activity

The potential of structurally new ferrocene-functionalized guanidines as redox-active precursors for the synthesis of heterometallic platinum­(II)–guanidine complexes with anticancer activity was studied. To this end, an atom-economical catalytic approach was followed by using ZnEt₂ to catalyze the addition of aminoferrocene and 4-ferrocenylaniline to <i>N</i>,<i>N</i>′-diisopropylcarbodiimide. Furthermore, reaction of a platinum­(II) source with the newly obtained guanidines Fc–NC­(NHⁱPr)₂ (<b>3</b>) and Fc­(1,4-C₆H₄)–NC­(NHⁱPr)₂ (<b>4</b>) provided access to the heterometallic complexes [PtCl₂{Fc–NC­(NHⁱPr)₂}­(DMSO)] (<b>5</b>), [PtCl₂{Fc­(1,4-C₆H₄)–NC­(NHⁱPr)₂}­(DMSO)] (<b>6</b>), and [PtCl₂{Fc­(1,4-C₆H₄)–NC­(NHⁱPr)₂}₂] (<b>7</b>). Electrochemical studies evidence the remarkable electronic effect played by the direct attachment of the guanidine group to the ferrocene moiety in <b>3</b>, making its one-electron oxidation extremely easy. Guanidine-based Fe–Pt complexes <b>5</b> and <b>6</b> are active against all human cancer cell lines tested, with GI₅₀ values in the range 1.4–2.6 μM, and are more cytotoxic than cisplatin in the resistant T-47D and WiDr cell lines