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

Abstract

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...