Structural and electronic factors are crucial to rationalizethedifferent N,O or N,N chelating coordination of pyrazolones containinga pyridine ring. The reactivity of proligand 3-phenyl-1-(pyridin-2-yl)-5-pyrazolone(HLpy,ph) with the (arene)Ru(II) fragment was explored.Neutral and ionic (arene)Ru(II) complexes were obtained and fullycharacterized, also by X-ray diffraction, revealing the ligand tocoordinate in an unusual N,O-chelatingfashion. Other ruthenium complexes were also synthesized with 3-methyl-1-(pyridin-2-yl)-5-pyrazolone(HLpy,me) and 3-methyl-1-(pyridin-2-yl)-4-trifluoroacetyl-5-pyrazolone(HQ(py,CF3)). In these complexes the ligands adopt the preferred N,N-chelating mode. Ligands and complexeswere theoretically analyzed by density functional theory (DFT). Themost stable tautomer of HLpy,ph matched well with the experimentalbehavior of this proligand and the structures of Ru-complexes werewell described by calculations. The thermodynamic stability of the N,O- and N,N-coordination modes was analyzed and a proposal for the achievementof the N,O-coordination mode incomplexes 1-4 was proposed. Cytotoxicitytests were performed against human ovarian carcinoma (A2780 and Cisplatin-resistantA2780cis) and nontumorigenic human embryonic kidney (HEK293T) celllines, showing the free ligands to be more cytotoxic that the ensuing(arene)Ru(II) complexes.