Ruthenium(II) and Iridium(III) Complexes as Tested Materials for New Anticancer Agents

The oncological use of cisplatin is hindered by its severe side effects and a very important resistance problem. To overcome these problems, scientists have attempted to design new generation transition-metal anticancer complexes. In this study, we present new complexes, ruthenium(II) [(η⁶-p-cymene)RuCl(py₂CO)]PF₆ (1), iridium(III) [(η⁵-Cp)IrCl(py₂CO)]PF₆ (2), and NH₄[IrCl₄(py₂CO)]·H₂O (3), based on di-2-pyridylketone (py₂CO). The prepared complexes were characterized by FTIR, ¹H, ¹³C, ¹⁵N NMR, UV-Vis, PL and elemental analysis techniques. The single-crystal X-ray structure analysis and comparative data revealed pseudo-octahedral half-sandwich 1 and 2 complexes and octahedral tetrachloroiridate(III) 3 with a rare chelating κ²N,O coordination mode of py₂CO. The compounds were tested in vitro against three cancer cell lines-colorectal adenoma (LoVo), myelomonocytic leukaemia (MV-4-11), breast adenocarcinoma (MCF-7), and normal fibroblasts (BALB/3T3). The most promising results were obtained for iridium(III) complex 3 against MV-4-11 (IC₅₀ = 35.8 ± 13.9 µg/mL) without a toxic effect against normal BALB/3T3, which pointed towards its selectivity as a potential anticancer agent. Extensive research into their mode of binding with DNA confirmed for 1 and 2 complexes non-classical binding modes, while the 3D circular dichroism (CD) experiment (ΔT_m) suggested that 3 induced the probable formation of covalent bonds with DNA. In addition, the obtained iridium complexes induce ROS, which, in synergy with hydrolysis promoting DNA bonding, may lead to cancer cell death.