Chemical Characterization and Biological Evaluation of New Cobalt(II) Complexes with Bioactive Ligands, 2-Picolinehydroxamic Acid and Reduced Schiff Base N-(2-Hydroxybenzyl)alanine, in Terms of DNA Binding and Antimicrobial Activity

Abstract

Five new heteroligand cobalt(II) complexes with 2-picolinehydroxamic acid and reduced Schiff base, N-(2-hydroxybenzyl)alanine, were formed in an aqueous solution over a wide pH range. The coordination properties of ligands towards the metal ion were determined using a pH-metric method, and then the speciation model was confirmed by UV–Vis studies. A stacking interaction between the Schiff base phenol ring and the 2-picolinehydroxamic acid pyridine ring was found to improve the stability of the heteroligand species, indicating more effective coordination in mixed-ligand complexes than in their respective binary systems. The antimicrobial properties of heteroligand complexes were determined against Gram-negative and Gram-positive bacteria, as well as fungal strains. The formulation demonstrated the highest bacteriostatic and bactericidal activity (3.65 mM) against two strains of Gram-negative Helicobacter pylori bacteria and towards Candida albicans and Candida glabrata; this is important due to the potential co-existence of these microorganisms in the gastric milieu and their role in the development of gastritis. The binary complexes in the cobalt(II)—2-picolinehydroxamic acid system and 2-picolinehydroxamic acid were not cytotoxic against L929 mouse fibroblasts, neither freshly prepared solutions or after two weeks’ storage. By comparison, the heteroligand complexes within the range 0.91–3.65 mM diminished the metabolic activity of L929 cells, which was correlated with increased damage to cell nuclei. The concentration of the heteroligand species increased over time; therefore, the complexes stored for two weeks exhibited stronger anticellular toxicity than the freshly prepared samples. The complexes formed in an aqueous solution under physiological pH effectively bound to calf thymus DNA in an intercalative manner. This DNA-binding ability may underpin the antimicrobial/antifungal activity of the heteroligand complexes and their ability to downregulate the growth of eukaryotic cells.

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

“…The MIC/MBC/MCF values of the classical antibiotics ( Table 2 ) present significant quantitative differences in relation to the tested compounds. As in the case of other aqueous systems [33] , [44] , the high MIC/MBC/MCF values for the Co(II)–PhAlaSal system result from the fact that they are determined for the total concentration of all complexes present in solution at pH 7.5, i.e. [CoL], [CoL 2 H] - and [CoL 2 ] 2- ( Fig.…”

“…Most likely, the other two phenolic groups are bound to the metal ion through the axial sites. This mode of coordination affects the different planes of the ligand molecules and thus prevents the destabilization of the complex caused by the electrostatic repulsion between negatively-charged, uncoordinated carboxyl groups [44] , [46] .…”

“…This made it possible to perform spectrophotometric measurements while controlling the pH value. The application of the combined polymer microelectrode enabled spectrophotometric studies in a perchlorate environment, as the nitrate ions used in the potentiometric part show significant absorption in the 300 nm region ( ε ≈ 8), attributed to the n → π* transition [44] . Thus, pH and ionic strength ( I = 1.0 M) were adjusted by HClO 4 and NaClO 4 , respectively.…”

“…Antibacterial or antifungal activities were determined using broth microdilution assay according to European Committee on Antimicrobial Susceptibility (EUCAST) recommendations, as previously described [44] . The antimicrobial activity of the formulations was assessed on the basis of minimal inhibitory concentrations (MIC), minimal bactericidal concentrations (MBC) and minimal fungicidal concentrations (MFC).…”

Halogenated non-innocent vanadium(v) Schiff base complexes: chemical and anti-proliferative properties

“…Based on the data shown in Figure 6, we were able to plot the absorbances as a function of time and determine the half-lives (t 1/2 ) in the mixed DMSO:PBS solution, which are listed in Table 1. The order to the stability, with the least-stable compounds first, is: [37][38][39][40][41][42] Direct injection can reduce undesirable redox chemistry and stabilize the drug in the reducing tumor environment. [37][38][39][40][41][42][43][44][45][46] The generation of reactive oxygen species (ROS), [37][38][39][40][41][42] changes with the type of cancer, 43 the state of the cancers adaptability and ROS generation within the cells.…”