The influence of ancillary ligands on the antitumoral activity of new cyclometallated Pt(II) complexes derived from an ferrocene-pyrazole hybrid

The study of the cycloplatination of the ferrocenyl-pyrazole [1-{MeO(CH2)2}-3,5-Ph2-4-(CH2Fc)-(C3N2)] (1) has allowed us to isolate and characterize the trimetallic compound [Pt{(κ2-C,N)[1-[MeO(CH2)2]-3-(C6H4)-5-Ph-4-(CH2Fc)-(C3N2)]}(1)Cl] (3) that contains two units of ligand 1 adopting two different binding modes. Further studies of the reactivity of compound 3 with PPh3 in the absence or in the presence of AgNO3 gave the heterodimetallic complexes [Pt{(κ2-C,N)[1-[MeO(CH2)2]-3-(C6H4)-5-Ph-4-(CH2Fc)-(C3N2)]}(X)(PPh3)] [X = Cl− (4) and NO2− (5)]. The X-ray crystal structures of 3·1/2CH2Cl2 and 5·CH2Cl2 confirmed: a) the existence of heterotri- (in 3) or dimetallic molecules (in 5), b) the mode of binding of ligand 1, and c) the presence of N-bonded NO2− ligand (in 5). Comparative studies of the cytotoxic activity of the new products in the MCF7 and MDA-MB-231 (breast) and in the cisplatin resistant HCT116 (colon) cancer cell lines reveal that the potency of the metallacycles depends on the nature of the ancillary ligands (X and L) and increases according to the sequence 3 (L = 1 and X = Cl−) «5 (L = PPh3 and X = NO2−)