Synthesis, Characterisation, and Biological Activity of the Ruthenium Complexes of the N4-Tetradentate (N4-TL), 1,6-Di(2′-pyridyl)-2,5-dimethyl-2,5-diazahexane (picenMe2)

A series of complexes of the type rac-[Ru(N4-TL)(PL)]2+ (where N4-TL = 1,6-di(2′-pyridyl)-2,5-dimethyl-2,5-diazahexane (picenMe2, N4-TL-2) and PL = 1,10-phenanthroline (phen, Ru-2), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq, Ru-3), 7,8-dimethyl-dipyrido[3,2-a:2′,3′-c]phenazine (dppzMe2, Ru-4), 2-phenyl-1H-imidazo[4,5-f][1,10]phenanthroline (phenpyrBz, Ru-5), 2-(p-tolyl)-1H-imidazo[4,5-f][1,10]phenanthroline (phenpyrBzMe, Ru-6), and 2-(4-nitrophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline (phenpyrBzNO2, Ru-7), were synthesised. All structures were confirmed using NMR, electrospray ionisation mass spectrometry (ESI-MS), high-performance liquid chromatography (HPLC), and UV analysis and for four complexes X-ray crystallography. The in vitro cytotoxicity assays revealed that Ru-6 was 5, 10, and 40-fold more potent than oxaliplatin, cisplatin, and carboplatin, respectively.