Ga complexes of 8-hydroxyquinoline-2-carboxylic acid: Chemical speciation and biological activity

The binding ability of 8-hydroxyquinoline-2-carboxylic acid (8-HQA) towards Ga3+ has been investigated by ISEH+ (Ion Selective Electrode, glass electrode) potentiometric and UV/Vis spectrophotometric titrations in KCl(aq) at I = 0.2 mol dm(-3) and at T = 298.15 K. Further experiments were also performed adopting both the metal (with Fe3+ as competing cation) and ligand-competition approaches (with EDTA as competing ligand). Results gave evidence of the formation of the [Ga(8-HQA)](+), [Ga(8-HQA)(OH)], [Ga(8-HQA)(OH)(2)](-) and [Ga(8-HQA)(2)](-) species, the latter being so far the most stable, as also confirmed by ESI-MS analysis. Experiments were also designed to determine the stability constants of the [Ga(EDTA)](-) and [Ga(EDTA)(OH)](2-) in the above conditions. Due to the relevance of Ga3+ hydrolysis in aqueous systems, literature data on this topic were collected and critically analyzed, providing equations for the calculation of mononuclear Ga3+ hydrolysis constants at T = 298.15 K, in different ionic media, in the ionic strength range 0 < I / mol dm(-3) <= 1.0. The synthesis and characterization (by ElectroSpray Ionization - Mass Spectrometry (ESI-MS), Attenuated Total Reflectance - Fourier-Transform Infrared Spectroscopy (ATR-FTIR) and ThermoGravimetric Analysis (TGA)) of Ga3+/8-HQA complexes were also performed, identifying [Ga(8-HQA)(2)](-) as the main isolated species, even in the solid state. Finally, the potential effects of 8-HQA and Ga3+/8-HQA complex towards human microbiota exposed to ionizing radiation were evaluated (namely Actinomyces viscosus, Streptococcus mutans, Streptococcus sobrinus, Pseudomonas putida, Pseudomonas fluorescens and Escherichia coli), as well as their anti-proliferative and anti-inflammatory properties. A radioprotective effect of Ga3+/8-HQA complex was observed on Actinomyces viscosus, while showing a potential radiosensitizing effect against Streptococcus mutans and Streptococcus sobrinus. No cytotoxicity on RAW264.7 murine macrophage cells was observed, neither for the free ligand or Ga3+/8-HQA complex. Nevertheless, Ga3+/8-HQA complex highlighted potential anti-inflammatory properties.