Complexes in aqueous cobalt(II)-2-picolinehydroxamic acid system: Formation equilibria, DNA-binding ability, antimicrobial and cytotoxic properties

Abstract

The coordination properties of 2-picolinehydroxamic acid towards cobalt(II) in aqueous solution were determined by a pH-metric method and confirmed by spectroscopic (UV-Vis and ESI-MS) studies. The results show the formation of mononuclear complexes, as well as of metallacrowns (MC). All methods indicate a high tendency of 2-picolinehydroxamic acid to form cobalt(II) metallacrown 12-MC-4. ESI-MS additionally confirms 15-MC-5 and 18-MC-6, stabilized by a sodium ion and methanol. The complexes observed in the speciation model at a pH about 7.2 were studied for their DNA-binding ability. The decrease of absorbance in the range of ca 310-400 nm indicates effective binding to calf thymus DNA by 2-picolinehydroxamic acid complexes, via intercalative mode. The antimicrobial properties of 2-picolinehydroxamic acid, cobalt(II) ions and of the complexes formed in the Co(II) - ligand system were determined against Gram-positive bacteria (Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, Bacillus subtilis), Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli, Helicobacter pylori) and fungal strains (Candida, Aspergillus niger). The results indicate that the complexes demonstrate greater antibacterial and antifungal activity for most strains than the ligand. Both the complexes and the ligand induce a slight decrease in the metabolic activity of cells, while the complexes do not damage the cell nuclei. The 2-picolinehydroxamic acid complexes activate the human monocytic cells, suggesting they have immunomodulating properties, which are particularly important in combating infections caused by strains resistant to other drugs.

Keywords: 2-Picolinehydroxamic acid; Antimicrobial activity; Cobalt(II) complexes; DNA interaction; UV-Vis spectroscopy; pH potentiometry.