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

Abstract

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.