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 1H 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+, [GaL2]+ and [GaL3] 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.