Half-sandwich ruthenium, rhodium and iridium complexes featuring oxime ligands: Structural studies and preliminary investigation of in vitro and in vivo anti-tumour activities

摘要

Half-sandwich ruthenium, rhodium and iridium complexes (1-12) were synthesized with aldoxime (L1), ketoxime (L2) and amidoxime (L3) ligands. Ligands have the general formula [PyC(R)NOH], where R = H (L1), R = CH3 (L2) and R = NH2 (L3). Reaction of [{(arene) MCl2}(2)] (arene = p-cymene, benzene, Cp*; M = Ru, Rh, It) with ligands L1-L3 in 1: 2 metal precursor-to-ligand ratio yielded complexes such as [{(arene)ML kappa(2) Cl-(N boolean AND N)}]PF6. All the ligands act as bidentate chelating nitrogen donors in kappa(2) ((N boolean AND N)) fashion while forming complexes. In vitro anti-tumour activity of complexes 2 and 10 against HT-29 (human colorectal cancer), BE (human colorectal cancer) and MIA PaCa-2 (human pancreatic cancer) cell lines and non-cancer cell line ARPE-19 (human retinal epithelial cells) revealed a comparable activity although complex 2 demonstrated greater selectivity for MIA PaCa-2 cells than cisplatin. Further studies demonstrated that complexes 3, 6, 9 and 12 induced significant apoptosis in Dalton's ascites lymphoma (DL) cells. In vivo anti-tumour activity of complex 2 on DL-bearing mice revealed a statistically significant antitumour activity (P = 0.0052). Complexes 1-12 exhibit HOMO-LUMO energy gaps from 3.31 to 3.68 eV. Time-dependent density functional theory calculations explain the nature of electronic transitions and were in good agreement with experiments.