New Ru(II) half sandwich complexes bearing the N,N′ bidentate 9-ethyl-N-(pyridin-2-ylmethylene)9H-carbazole-3-amine ligand: Effects of halogen (Cl−, Br− and I−) leaving groups versus in vitro activity on HepG2 cancer cells, cell cycle, fluorescence study, cellular accumulation and DFT study

Abstract

Three new ruthenium(II) complexes [(η6-p-cymene)RuX(L)]PF6 (X = Cl (1), Br (2) and I (3)) with 9-ethyl-N-(pyridin-2-ylmethylene)9H-carbazole-3-amine (L) have been prepared and characterised by elemental analysis and different spectral techniques (NMR studies, IR and HR-Mass spectroscopy). The molecular structure of the [(η6-p-cymene)RuI(L)]PF6 (3) complex was determined by single crystal XRD. The geometry around the Ru(II) centre is that of a classical “piano stool” with the iodine, the N,N′ ligand bonding in a bidentate manner and the π-bonds of the p-cymene occupying the coordination sites. In vitro studies of the complexes 1–3 on HepG2 human liver cancer cells showed excellent inhibitory concentration (IC50) values between 22 and 30 μM. The halogen leaving groups Cl−, Br− and I− presented in the complexes 1–3 showed a significant effect. Interestingly complex 3 displayed a significant growth inhibitory IC50 value of 22 μM compared to the other two complexes. Furthermore, cell cycle, cytotoxic, nuclear studies and cellular accumulation have shown that the new Ru(II) half sandwich complexes 1–3 were effective against HepG2 cancer cell proliferation. Density functional theory (DFT) was used to calculate the relevant molecular orbital energy levels, binding energies, bond angles and bond lengths of the synthesised Ru(II) complexes. The DFT study of the complexes 1–3 further supported the biological activity of the complexes and showed good agreement with experimental results.