Agnieszka Chylewska

Coordinate cis-[Cr(C2O4)(pm)(OH2)2]+ Cation as Molecular Biosensor of Pyruvate’s Protective Activity Against Hydrogen Peroxide Mediated Cytotoxity

In this paper instrumental methods of carbon dioxide (CO2) detection in biological material were compared. Using cis-[Cr(C2O4)(pm)(OH2)2]+ cation as a specific molecular biosensor and the stopped-flow technique the concentrations of CO2 released from the cell culture medium as one of final products of pyruvate decomposition caused by hydrogen peroxide were determined. To prove the usefulness of our method of CO2 assessment in the case of biological samples we investigated protective properties of exogenous pyruvate in cultured osteosarcoma 143B cells exposed to 1 mM hydrogen peroxide (H2O2) added directly to culture medium. Pyruvic acid is well known scavenger of H2O2 and, moreover, a molecule which is recognized as one of the major mediator of oxidative stress detected in many diseases and pathological situations like ischemia-reperfusion states. The pyruvates antioxidant activity is described as its rapid reaction with H2O2, which causes nonenzymatic decarboxylation of pyruvate and releases of CO2, water and acetate as final products. In this work for the first time we have correlated the concentration of CO2 dissolved in culture medium with pyruvates oxidant-scavenging abilities. Moreover, the kinetics of the reaction between aqueous solution of CO2 and coordinate ion, cis-[Cr(C2O4)(pm)(OH2)2]+ was analysed. The results obtained enabled determination of the number of steps of the reaction studied. Based on the kinetic equations, rate constants were determined for each step.

Spectrophotometric, potentiometric, and conductometric studies of binary complex formation between copper(II) and three forms of vitamin B6 in aqueous solutions

This article reports the detailed study concerning the mode of binding of three forms of vitamin B6, pyridoxamine (pm), pyridoxine (pn), and pyridoxal (pl), with Cu(II) in aqueous solutions using three independent methods: potentiometry, conductometry, and UV–vis spectroscopy. The stability constants of complexes formed between copper(II) and vitamin B6 were investigated by potentiometric titration in 0.1 M KNO3 ionic medium at 25 °C. While drawing the relations between molar conductance and the ratio of metal to ligand concentrations, different types of lines were obtained indicating the formation of 1 : 1 and 1 : 2 stoichiometric compounds. The stability constants have been determined using EQUID and CVEQUID computer programs and the obtained results were in agreement. The relatively high values of stability constants of Cu(II)-vitamin B6 complexes obtained from three independent methods in comparison to those with other competing cations suggest that the complexes studied are relatively stable in aqueous solutions.

Coordination mode and reactivity of nickel(II) with vitamin B6

This contribution presents a selection of results obtained using spectrophotometric and potentiometric titrations. For several reasons, the investigated equilibria present particular challenges to traditional analysis techniques. Equilibrium constants and UV–vis absorption spectra for different ligands in the complexation process of Ni(II) with pyridoxamine (pm), pyridoxal (pl) and pyridoxine are reported. The gradual and cumulative stability constants occurring in aqueous solution are presented for all complexes studied. Additionally, crystal-field parameters were calculated for two nickel(II) complexes synthesized, [Ni(pm)2]Cl2 and [Ni(pl)2]Cl2, respectively. The minimum inhibitory concentration and minimal bactericidal/fungicidal concentration values for Ni(II) complexes studied were obtained at 25 °C for 24–48 h. The activity data show that the complexes are more potent antimicrobials than the parent ligands. Graphical Abstract

Potassium trans-(bis(oxalato)diaquacobaltate(II)) tetrahydrate: synthesis, structure, potentiometric and thermal studies

The title compound, trans-K2[Co(C2O4)2(H2O)2]·4H2O, was synthesised, and characterised by elemental analysis. Acid dissociation constants for the complex were determined by potentiometric titration and calculated by STOICHIO program. The crystal structure of trans-K2[Co(C2O4)2(H2O)2]·4H2O was determined by X-ray diffraction studies. The asymmetric part of the unit cell contains one symmetric anion of oxalate and water molecule bound with Co(II) ion in crystallographic special position, one potassium cation and two molecules of water. Thermal properties of the complex were examined by thermogravimetric analysis (TGA). A decomposition mechanism is proposed on the basis of the results.

Coordination chemistry of pyrazine derivatives analogues of PZA: design, synthesis, characterization and biological activity

Ru(III) complexes with pyrazine derivatives: 2,3-bis(2-pyridyl)pyrazine (DPP), pyrazine-2-amidoxime (PAOX), pyrazine-2-thiocarboxamide (PTCA) and 2-amino-5-bromo-3-(methylamino)pyrazine (ABMAP) have been prepared. Characterization of the compounds was acquired using UV-Vis and FT-IR spectroscopy, elemental analysis, conductivity and electrochemical measurements as well as thermogravimetric studies. The ligand field parameters, Δ0 (splitting parameter), B (Racah parameter of interelectronic repulsion) and β (nephelauxetic ratio) were calculated. The stabilities of the Ru(III) complexes have also been confirmed by spectrophotometric titration methods in acetonitrile and water solutions. The data showed that the examined compounds are stable both in solution and solid states, which was also confirmed by the values of their stability constants found. Moreover, the molecular structures of the complexes have been optimized using AM1 and PM3 methods and this supported octahedral geometry around the Ru(III) ion. The minimum inhibitory (MIC) and minimum bactericidal concentration (MBC) for synthesized complexes were studied against two Gram (+) bacteria, two Gram (−) bacteria and fungi – three reference strains of Candida albicans. The results show that [RuCl(PAOX)2(OH2)]Cl2 display antifungal activity.

Metallopharmaceuticals in Therapy - A New Horizon for Scientific Research

Coordination chemistry offers much scope for the design of novel and therapeutic agents, including metallopharmaceuticals. The widespread use of metal complexes as effective pharmaceuticals, e.g. cancer therapeutic, anti-inflammatory, antidiabetic drugs or antimicrobial and diagnostic agents, demonstrates that the cytotoxicity of metal ions can be finely controlled via the appropriate choice of ligands. The successful targeting of radioisotopes again depends on the ligand design and metal oxidation state. The complexes of platinum, ruthenium, cobalt, copper and other d-block metal ions have been used in medicine for a long time but only recent advances have been made in understanding the molecular basis of mechanism of their action. Due to the above mentioned purpose, we decided to prepare a detailed description of target-based research, directed towards a design and application possibilities, with the known mechanisms of action of metal ion complexes in the broad sense of therapy definition. The review also covers the progress, limitations and challenges of the above-mentioned approaches and emphasizes the advantages of well known and new metallopharmaceuticals in medicine and pharmacy.

Antifungal Activity and Mechanism of Action of the Co(III) Coordination Complexes With Diamine Chelate Ligands Against Reference and Clinical Strains of Candida spp.

Although many antifungal agents are available in clinical treatment, increasing resistance of fungi, especially Candida species, to the available drugs requires the development of new safe and non-toxic compounds with novel modes of action as effective treatment against resistant microorganisms. Cobalt complexes are very interesting and attractive as potential candidates with antimicrobial activity. Their therapeutic uses as antiviral, antibacterial antifungal, antiparasitic, antitumour, transferrin transporters, and anti-inflammatory agents are being intensively investigated. In this study we examined the antifungal activity of Co(III) complexes with diamine chelate ligands against a broad spectrum of Candida species. Minimum inhibitory concentration was determined by the microbroth dilution method and with serial passaging assay; the synergistic antimicrobial activity of the tested complexes combined with two antifungal drugs (ketoconazole and amphotericin B) was made by checkerboard assay. The effects of Co(III) complexes on yeast cell morphology were studied by optical and transmission electron microscopy. The mode of action of Co(III) complexes on the yeast cell wall (sorbitol assay) and cell membrane (ergosterol assay) were investigated. The cytotoxic effects of the tested compounds on red blood cells and the human keratinocyte (HaCaT) cell line were also evaluated. The analyzed compounds revealed significant antifungal activity for selected strains of Candida species; [CoCl2(dap)2]Cl (1) and [CoCl2(en)2]Cl (2) were more effective than ketoconazole. Its probable mechanism of action did not involve the cell wall or ergosterol binding. However, the checkerboard assay showed, that the antifungal activity of ketoconazole increased in combination with the tested complexes of Co(III). Our results suggest that both diamine complexes with Co(III) analogs caused damage to mitochondrial membrane or the membrane of the endoplasmic reticulum. The effect was observed by transmission electron microscope. Co(III) complexes with diamine chelate ligands are non-toxic at concentrations active against Candida species. This study provides new data on potential antifungal drugs, especially against Candida species.

Crystalline pyrazine-2-amidoxime isolated by diffusion method and its structural and behavioral analysis in the context of crystal engineering and microbiological activity

Pyrazine-2-amidoxime (PAOX) is a structural analogue of a popular drug, i.e. pyrazine-2-carboxamide (PZA). The crystalline PAOX was obtained by diffusion as a method of crystallization. Various types of intermolecular interactions between the H-bond donors (CH, NH, and OH) and H-bond acceptors (hydroxyl O, imino N, aza N) were found between PAOX molecules in X-ray diffraction studies. It was observed in the crystal structure that PAOX forms not only dimers but also stable helical-like polymers, stabilized by intermolecular interactions between two neighbouring molecules. Their geometric, energetic and spectroscopic properties were also characterised by DFT methods. Thermal decomposition of PAOX was examined with the use of a TG-IR analysis (20–1000 °C), and the results were further resolved. Electrochemical behaviour of the compound studied in acetonitrile in the absence or presence of methanol was described in detail, and mechanisms of the anodic oxidation and cathodic reduction were proposed. The complexometric properties of PAOX were examined against selected d-block metal ions in acetonitrile, as well as in aqueous solution. Biological assay of PAOX was performed to determine the antimicrobial activity and potential pharmaceutical applications. The minimum inhibitory (MIC) and minimal bactericidal (or fungicidal) concentrations (MBC/MFC) for PAOX were determined against six microorganisms.