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 N,N′-diisopropylcarbodiimide. Furthermore, reaction of a platinum­(II) source with the newly obtained guanidines Fc–NC­(NHiPr)2 (3) and Fc­(1,4-C6H4)–NC­(NHiPr)2 (4) provided access to the heterometallic complexes [PtCl2{Fc–NC­(NHiPr)2}­(DMSO)] (5), [PtCl2{Fc­(1,4-C6H4)–NC­(NHiPr)2}­(DMSO)] (6), and [PtCl2{Fc­(1,4-C6H4)–NC­(NHiPr)2}2] (7). Electrochemical studies evidence the remarkable electronic effect played by the direct attachment of the guanidine group to the ferrocene moiety in 3, making its one-electron oxidation extremely easy. Guanidine-based Fe–Pt complexes 5 and 6 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.