Catalytically Generated Ferrocene-Containing Guanidines as Efficient Precursors for New
Redox-Active Heterometallic Platinum(II) Complexes with Anticancer
Activity
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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 ZnEt<sub>2</sub> 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–NC(NH<sup>i</sup>Pr)<sub>2</sub> (<b>3</b>) and Fc(1,4-C<sub>6</sub>H<sub>4</sub>)–NC(NH<sup>i</sup>Pr)<sub>2</sub> (<b>4</b>) provided access to the heterometallic
complexes [PtCl<sub>2</sub>{Fc–NC(NH<sup>i</sup>Pr)<sub>2</sub>}(DMSO)] (<b>5</b>), [PtCl<sub>2</sub>{Fc(1,4-C<sub>6</sub>H<sub>4</sub>)–NC(NH<sup>i</sup>Pr)<sub>2</sub>}(DMSO)] (<b>6</b>), and [PtCl<sub>2</sub>{Fc(1,4-C<sub>6</sub>H<sub>4</sub>)–NC(NH<sup>i</sup>Pr)<sub>2</sub>}<sub>2</sub>] (<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 GI<sub>50</sub> values in the range 1.4–2.6
μM, and are more cytotoxic than cisplatin in the resistant T-47D
and WiDr cell lines
