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 guaiiidines 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,M-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(NH1Pr)(2)}(DMSO)] (5), [PtCl2{Fc(1,4-C6H4) N=C(NH1Pr)(2)}(DMSO)] (6), and [PtC12{Fc(1,4-C6H4) N-C=N=((NHPr)-Pr-i)(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 GI(50) values in the range 1.4-2.6 mu M and are more cytotoxic than cisplatin in the resistant T-47D and WiDr cell lines.