title: Comparative solution equilibrium studies of anticancer gallium(III) complexes of 8-hydroxyquinoline and hydroxy(thio)pyrone ligands.
abstract: The stoichiometry and stability constants of the Ga(III) complexes of 8-hydroxyquinoline (HQ), 8-hydroxyquinoline-5-sulfonate (HQS), maltol, thiomaltol, allomaltol and thioallomaltol were determined by means of pH-potentiometry, UV-vis spectrophotometry, spectrofluorometry and (1)H NMR spectroscopy in aqueous solution. Spectrofluorometry was used to determine the stability constants of the Ga(III)-HQ species in water. Formation of [GaL](2+), [GaL(2)](+) and [GaL(3)] complexes was found and the Ga(III) binding ability of the ligands followed the order: thioallomaltol<thiomaltol<allomaltol<maltol≪HQS~HQ. As a result of the outstanding stability of tris(8-hydroxyquinolinato)gallium(III) (KP46) the dissociation of the complex is negligible at physiological pH even in the biologically relevant low concentration range. Thus KP46 is able to preserve its original entity more considerably than other Ga(III) complexes. Moreover, intrinsic fluorescence of KP46 allows the monitoring of the cellular accumulation and distribution in human cancer cells by fluorescence microscopy.
authors.affiliation: Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, H-6720 Szeged, Hungary. enyedy@chem.u-szeged.hu
authors.forename: Éva A
authors.initials: ÉA
authors.lastname: Enyedy
authors.forename: Orsolya
authors.initials: O
authors.lastname: Dömötör
authors.forename: Erika
authors.initials: E
authors.lastname: Varga
authors.forename: Tamás
authors.initials: T
authors.lastname: Kiss
authors.forename: Robert
authors.initials: R
authors.lastname: Trondl
authors.forename: Christian G
authors.initials: CG
authors.lastname: Hartinger
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Keppler
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000737:chemistry* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005708:Gallium / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D015125:Oxyquinoline / Q000031:analogs & derivatives* / Q000737:chemistry*; D011199:Potentiometry; D011753:Pyrones / Q000737:chemistry*; D012996:Solutions; D013050:Spectrometry, Fluorescence
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D008024:Ligands; D011753:Pyrones; D012996:Solutions; C550316:allomaltol; C008316:maltol; D015125:Oxyquinoline; C013053:8-hydroxyquinoline-5-sulfonic acid; D005708:Gallium