10.1021/jm4007615.s002 Nicholas Lease Nicholas Lease Vadim Vasilevski Vadim Vasilevski Monica Carreira Monica Carreira Andreia de Almeida Andreia de Almeida Mercedes Sanaú Mercedes Sanaú Pipsa Hirva Pipsa Hirva Angela Casini Angela Casini María Contel María Contel Potential Anticancer Heterometallic Fe–Au and Fe–Pd Agents: Initial Mechanistic Insights American Chemical Society 2013 cisplatin PARP kidney cell line 2780R 2780S cytotoxic trimetallic derivatives M 2Fe MCF 7 cell lines PdCl breast cancer cells cancer cells DNA HEK complex Initial Mechanistic InsightsA series AuCl 2013-07-25 00:00:00 Dataset https://acs.figshare.com/articles/dataset/Potential_Anticancer_Heterometallic_Fe_Au_and_Fe_Pd_Agents_Initial_Mechanistic_Insights/2392906 A series of gold­(III) and palladium­(II) heterometallic complexes with new iminophosphorane ligands derived from ferrocenylphosphanes [{Cp-P­(Ph<sub>2</sub>)N-Ph}<sub>2</sub>Fe] (<b>1</b>), [{Cp-P­(Ph<sub>2</sub>)N-CH<sub>2</sub>-2-NC<sub>5</sub>H<sub>4</sub>}<sub>2</sub>Fe] (<b>2</b>), and [{Cp-P­(Ph<sub>2</sub>)N-CH<sub>2</sub>-2-NC<sub>5</sub>H<sub>4</sub>}­Fe­(Cp)] (<b>3</b>) have been synthesized and structurally characterized. Ligands <b>2</b> and <b>3</b> afford stable coordination complexes [AuCl<sub>2</sub>(<b>3</b>)]­ClO<sub>4</sub>, [{AuCl<sub>2</sub>}<sub>2</sub>(<b>2</b>)]­(ClO<sub>4</sub>)<sub>2</sub>, [PdCl<sub>2</sub>(<b>3</b>)], and [{PdCl<sub>2</sub>}<sub>2</sub>(<b>2</b>)]. The complexes have been evaluated for their antiproliferative properties in human ovarian cancer cells sensitive and resistant to cisplatin (A2780S/R), in human breast cancer cells (MCF7) and in a nontumorigenic human embryonic kidney cell line (HEK-293T). The highly cytotoxic trimetallic derivatives M<sub>2</sub>Fe (M = Au, Pd) are more cytotoxic to cancer cells than their corresponding monometallic fragments. Moreover, these complexes were significantly more cytotoxic than cisplatin in the resistant A2780R and the MCF7 cell lines. Studies of the interactions of the trimetallic compounds with DNA and the zinc-finger protein PARP-1 indicate that they exert anticancer effects in vitro based on different mechanisms of actions with respect to cisplatin.