title: Solution equilibria of anticancer ruthenium(II)-(η(6)-p-cymene)-hydroxy(thio)pyr(id)one complexes: impact of sulfur vs. oxygen donor systems on the speciation and bioactivity.
abstract: Stoichiometry and stability of antitumor ruthenium(II)-η(6)-p-cymene complexes of bidentate (O,O) hydroxypyrone and (O,S) hydroxythiopyr(id)one type ligands were determined by pH-potentiometry, (1)H NMR spectroscopy and UV-Vis spectrophotometry in aqueous solution and in dependence of chloride ion concentration. Formation of mono-ligand complexes with moderate stability was found in the case of the hydroxypyrone ligands (ethyl maltol and allomaltol) predominating at the physiological pH range. These complexes decompose to the dinuclear tri-hydroxido bridged species [{Ru(II)(η(6)-p-cymene)}2(OH)3](+) and to the metal-free ligand at basic pH values. In addition, formation of a hydroxido [Ru(II)(η(6)-p-cymene)(L)(OH)] species was found. The hydroxythiopyr(id)one ligands (thiomaltol, thioallomaltol, 3-hydroxy-1,2-dimethyl-thiopyridone) form complexes of significantly higher stability compared with the hydroxypyrones; their complexes are biologically more active, the simultaneous bi- and monodentate coordination of the ligands in the bis complexes (ML2 and ML2H) was also demonstrated. In the case of thiomaltol, formation of tris complexes is also likely at high pH. The replacement of the chlorido by the aqua ligand in the [Ru(II)(η(6)-p-cymene)(L)(Cl)] species was monitored, which is an important activation step in the course of the mode of action of the complexes, facilitating binding to biological targets.
authors.affiliation: Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, H-6720 Szeged, Hungary.
authors.forename: Eva A
authors.initials: EA
authors.lastname: Enyedy
authors.forename: Eva
authors.initials: E
authors.lastname: Sija
authors.forename: Tamás
authors.initials: T
authors.lastname: Jakusch
authors.forename: Christian G
authors.initials: CG
authors.lastname: Hartinger
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kandioller
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Keppler
authors.forename: Tamás
authors.initials: T
authors.lastname: Kiss
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D002712:Chlorides / Q000737:chemistry; D056831:Coordination Complexes / Q000737:chemistry*; D000081007:Cymenes; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D007477:Ions; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D039821:Monoterpenes / Q000737:chemistry*; D010100:Oxygen / Q000737:chemistry*; D011789:Quantum Theory; D012428:Ruthenium / Q000737:chemistry*; D012996:Solutions; D013455:Sulfur / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D002712:Chlorides; D056831:Coordination Complexes; D000081007:Cymenes; D007477:Ions; D039821:Monoterpenes; D012996:Solutions; C007210:4-cymene; D013455:Sulfur; D012428:Ruthenium; D010100:Oxygen
keywords: Allomaltol; Ruthenium antitumor complexes; Speciation; Stability constants; Thiomaltol