Equilibria of complexes in the aqueous cobalt(II)-N-(2-hydroxybenzyl)phenylalanine system and their biological activity compared to analogous Schiff base structures.

Due to their excellent prospects in biological applications, Schiff bases and their complexes are a source of continuing interest. The present study examines the formation of four cobalt(II) complexes with the reduced Schiff base N-(2-hydroxybenzyl)phenylalanine (PhAlaSal) in alkaline aqueous solution by pH-metry. UV-Vis and ESI-MS studies confirmed the model of proposed species. Kinetic analysis indicated that the single- and bi-ligand cobalt(II) complexes transitioned from octahedral to tetrahedral structures. The Schiff base and its complexes detected under physiological pH were tested for antimicrobial abilities and compared with analogous structures of the Schiff base derivative, N-(2-hydroxybenzyl)alanine (AlaSal). The ability of these structures to influence cell growth was tested on L929 mouse fibroblasts and on cervix and gastric adenocarcinoma cancer cell lines. N-(2-hydroxybenzyl)phenylalanine demonstrates greater antimicrobial efficacy than N-(2-hydroxybenzyl)alanine but also higher cytotoxicity; however, it is nonetheless effective against cancer cells. In turn, AlaSal demonstrates low cytotoxicity for fibroblasts and high cytotoxicity for gastric adenocarcinoma epithelial cells at bacteriostatic concentration for Helicobacter pylori and Candida strains. The presence of these microorganisms in the gastric milieu supports the development of gastritis and gastric cancer; AlaSal therapy may be simultaneously effective against both. Due to their cytotoxicity, Schiff base complexes are not suitable for use against fungal and bacterial infections, but may effectively prevent cancer cell growth. Data availability: Data will be made available on request.

Equilibria in Aqueous Cobalt(II)-Reduced Schiff Base N-(2-hydroxybenzyl)alanine System: Chemical Characterization, Kinetic Analysis, Antimicrobial and Cytotoxic Properties.

The present study describes the coordination properties of a reduced Schiff base, N-(2-hydroxybenzyl)alanine, towards cobalt(II) using potentiometric as well as spectroscopic (UV-Vis and ESI-MS) methods. The results indicate the formation of six mononuclear complexes showing high stability in aqueous solution. Coordination occurs in the {O-phenolic,N,O-carboxyl} and {N,O-carboxyl} chelation modes, depending on the degree of ligand deprotonation. Examination of the complexation equilibria at pH ca 7, which is important from a biological point of view, allowed to identify two species: [CoL] and [CoL2H]-. The kinetic analysis showed a structural change of those cobalt(II) complexes from octahedral to tetrahedral in accordance with a first-order time relationship. The antimicrobial properties of N-(2-hydroxybenzyl)alanine, cobalt(II) nitrate and of the Co(II) - ligand complexes were determined against Gram-positive bacteria (Enterococcus faecalis, Staphylococcus aureus, Staphylococcus epidermidis), Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli, Helicobacter pylori) and a fungal strain (Candida). The results indicate that the complexes are more active for more strains than the ligand alone. Nevertheless, the complexes induce a higher decrease in the metabolic activity of cells but without damage to nuclei. Tetrahedral structures show stronger anti-cellular toxicity than octahedral complexes, which is most likely due to the higher accessibility of the cobalt(II) center.

Spectroscopic Determination of Metal-Ligand Coordination by Biologically Active 2-Picolinehydroxamic Acid with Iron(III) and Oxidovanadium(IV) in Aqueous Solutions.

The complexing properties of 2-picolinehydroxamic acid towards iron(III) as well as oxidovanadium(IV) were characterized in aqueous solutions by the UV-Vis spectrophotometric method. The speciation models have been confirmed and even extended by electrospray-ionization mass spectrometry (ESI-MS) studies. For both systems, mononuclear complexes were formed below a pH of 1 and coordination by O,O- chelation mode leading to the formation of five-membered rings was confirmed. The overall stability constant values were determined and compared with other similar systems, indicating more effective binding of the ligand by Fe(III) than VO(IV). The acidic medium of the reaction in the VO(IV) - 2-picolinehydroxamic acid system prevented the oxidation of VO(IV) to V(V). 2-Picolinehydroxamic acid was chosen because of its previously evidenced biological properties. As a result of acidification, reversible dissociation of the complexes in both systems was observed, indicating the action of 2-picolinehydroxamic acid as a potential siderophore.

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

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.