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.

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.

The paper examines Co(II)–amino acid–imidazole systems (where amino acid = l-α-amino acid: alanine, asparagine, histidine) which, when in aqueous solutions, activate and reversibly take up dioxygen, while maintaining the structural scheme of the heme group (imidazole as axial ligand and O2 uptake at the sixth, trans position) thus imitating natural respiratory pigments such as myoglobin and hemoglobin. The oxygenated reaction shows higher reversibility than for Co(II)–amac systems with analogous amino acids without imidazole. Unlike previous investigations of the heteroligand Co(II)–amino acid–imidazole systems, the present study accurately calculates all equilibrium forms present in solution and determines the $$K_{{{\text{O}}_{2} }}$$ K O 2 equilibrium constants without using any simplified approximations. The equilibrium concentrations of Co(II), amino acid, imidazole and the formed complex species were calculated using constant data obtained for analogous systems under oxygen-free conditions. Pehametric and volumetric (oxygenation) studies allowed the stoichiometry of O2 uptake reaction and coordination mode of the central ion in the forming oxygen adduct to be determined. The values of dioxygen uptake equilibrium constants $$K_{{{\text{O}}_{2} }}$$ K O 2 were evaluated by applying the full mass balance equations. Investigations of oxygenation of the Co(II)–amino acid–imidazole systems indicated that dioxygen uptake proceeds along with a rise in pH to 9–10. The percentage of reversibility noted after acidification of the solution to the initial pH ranged within ca 30–60% for alanine, 40–70% for asparagine and 50–90% for histidine, with a rising tendency along with the increasing share of amino acid in the Co(II): amino acid: imidazole ratio. Calculations of the share of the free Co(II) ion as well as of the particular complex species existing in solution beside the oxygen adduct (regarding dioxygen bound both reversibly and irreversibly) indicated quite significant values for the systems with alanine and asparagine—in those cases the of oxygenation reaction is right shifted to a relatively lower extent. The experimental results indicate that the “active” complex, able to take up dioxygen, is a heteroligand CoL2L′complex, where L = amac (an amino acid with a non-protonated amine group) while L′ = Himid, with the N1 nitrogen protonated within the entire pH range under study. Moreover, the corresponding log $$K_{{{\text{O}}_{2} }}$$ K O 2 value at various initial total Co(II), amino acid and imidazole concentrations was found to be constant within the limits of error, which confirms those results. The highest log $$K_{{{\text{O}}_{2} }}$$ K O 2 value, 14.9, occurs for the histidine system; in comparison, asparagine is 7.8 and alanine is 9.7. This high value is most likely due to the participation of the additional effective N3 donor of the imidazole side group of histidine. The Co(II)–amac–Himid systems formed by using a [Co(imid)2]n polymer as starting material demonstrate that the reversible uptake of molecular oxygen occurs by forming dimeric μ-peroxy adducts. The essential impact on the electron structure of the dioxygen bridge, and therefore, on the reversibility of O2 uptake, is due to the imidazole group at axial position (trans towards O2). However, the results of reversibility measurements of O2 uptake, unequivocally indicate a much higher effectiveness of dioxygenation than in systems in which the oxygen adducts are formed in equilibrium mixtures during titration of solutions containing Co(II) ions, the amino acid and imidazole, separately.

Isothermal titration calorimetry (ITC), circular dichroism (CD) spectroscopy, and molecular dynamics simulations were applied to describe interactions between lipopeptides and decavanadate ions ([V₁₀O₂₈]⁶⁻). The selected lipopeptides are conjugates of the amide of the KR12 peptide, the smallest antimicrobial peptide derived from human cathelicidin LL-37, with lauric acid (C12-KR12) and myristic acid (C14-KR12). The smaller sizes of C12-KR12 and C14-KR12 compared to proteins allow for the rigorous characterization of their non-covalent interactions with highly negatively charged [V₁₀O₂₈]⁶⁻ ions. The stoichiometry of the resulting decavanadate–peptide complexes and the thermodynamic parameters (ΔG, ΔH, and TΔS) of the interactions were determined. The ITC results, supported by the MD simulation, showed that the binding of cationic lipopeptides for decavanadate is rather non-specific and is driven by enthalpic contributions resulting from electrostatic interactions between the positively charged residues of the peptides and the anionic decavanadate. Furthermore, the influence of temperature and the interactions with decavanadate ions on the stability of the α-helical structure of the lipopeptides were assessed based on CD spectra. Under the experimental conditions (50 mM sodium cacodylate buffer, pH 5), the peptides adopt an α-helical conformation, with C14-KR12 showing greater thermal stability. The interactions with vanadium species disrupt the α-helical structure and reduce its thermal stability.