Synthesis, structure, electrochemistry, and cytotoxic properties of ferrocenyl ester derivatives.

A series of ferrocenyl ester complexes, varying the lipophilic character of the pendant groups, was prepared and characterized by spectroscopic and analytical methods. The syntheses of Fe(C(5)H(4)CO(2)CH(3))(2), Fe(CpCOOCH(3)) (CpCOO CH(2)CH(3)), and Fe(CpCOOCH(2)CH(3))(2) are reported. The solid-state structure of Fe(C(5)H(4)CO(2)CH(3))(2) has been determined by X-ray crystallography. Fe(C(5)H(4)CO(2)CH(3))(2) has the cyclopentadienyl rings virtually in an eclipsed conformation with the pendant groups not completely opposite to each other. Cyclic voltammetry characterization showed that the functionalized ferrocenes oxidize at potentials, E(pa), higher than ferrocene as a result of the electro withdrawing effect of the pendant groups on the cyclopentadienyl ligand. The cytotoxicities of Fe(C(5)H(4)CO(2)CH(2)CH(2)OH)(2), Fe(C(5)H(4)CO(2)CH(2)CH=CH(2))(2), Fe(C(5)H(4)CO(2)CH(3))(2), Fe(CpCOOCH(3))(CpCOOCH(2)CH(3)), and Fe(CpCOOCH(2)CH(3))(2) in colon cancer HT-29 and breast cancer MCF-7 cell lines were measured by the MTT biological viability assay and compared to ferrocene and ferrocenium. Fe(C(5)H(4)CO(2)CH(2)CH=CH(2))(2) showed the best IC(50) values, 180(10) muM for HT-29 and 190(30) muM for MCF-7 cell lines, with cytotoxicities similar to ferrocenium. The cytotoxic data suggest that as we increase the lipophilic character of the functionalized ferrocene, the cytotoxicity improves approaching to the cytotoxic activity of ferrocenium.