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Isothermal titration calorimetry, circular dichroism (CD) techniques, and

The measurement of oxygen consumption is an important element in the understanding of an organism’s metabolic state. Oxygen is also a phosphorescence quencher, which allows the evaluation of phosphorescence emitted by oxygen sensors. Two Ru(II)-based oxygen-sensitive sensors were used to study the effect of chemical compounds [(1) = [CoCl2(dap)2]Cl, and (2) = [CoCl2(en)2]Cl (AmB = amphotericin B) against reference and clinical strains of Candidaalbicans. The tris-[(4,7-diphenyl-1,10-phenanthroline)ruthenium(II)] chloride ([Ru(DPP)3]Cl2) (Box) adsorbed onto the DavisilTM silica gel was embedded in the silicone rubber Lactite NuvaSil® 5091 and the coating on the bottom of 96-well plates. The water-soluble oxygen sensor (BsOx = tris-[(4,7-diphenyl-1,10-phenanthrolinedisulphonic acid disodium)ruthenium(II)] chloride ‘x’ hydrate = {Ru[DPP(SO3Na)2]3}Cl2 = water molecules were omitted in the BsOx formula) was synthesized and characterized by RP-UHPLC, LCMS, MALDI, elemental analysis, ATR, UV-Vis, 1H NMR, and TG/IR techniques. The microbiological studies were performed in the environment of RPMI broth and blood serum. Both Ru(II)-based sensors turned out to be useful in the study of the activity of Co(III) complexes and the commercial antifungal drug amphotericin B. In addition, a new activity of the oxygen sensor, the soluble Ru(II) complex BsOx, was demonstrated, which is a mixture with amphotericin B that caused a significant increase in its antifungal activity. Thus, it is also possible to demonstrate the synergistic effect of compounds active against the microorganisms under study.

The metal cations-polysaccharides complexes play crucial roles in the process of immune cell recognitions. Here, we create simpler biomimetic ligands, which emulate binding of carbohydrates in living organisms. We present a detailed study on the interactions of Cu2+, Ni2+ and VO2+ ions with t-butyl 3-azido- and 3-amino-2,3-dideoxy-α-d-arabino-hexopyranosides. NMR, IR and UV–Vis spectroscopies as well as single crystal X-ray diffraction were used for the ligand structure determinations and showed their binding affinity of ions selected. The formation of stable complexes of Cu(II), Ni(II), VO(IV) ions and saccharides with 1:1, 1:2 and 1:3 molar ratios was proved. The coordination sites proposed are N-donor (amino or azido groups), O-donor (hydroxyl group) and endo-oxygen atoms. Additionally, parameters like shape, charge density distribution, and sites of chemical reactivity of the sugars studied were obtained by mapping electron density isosurface with electrostatic potential (MESP).

Assessment of bacterial growth is an essential tool in many fields of study. Numerous methods are available for that purpose, but they are not without disadvantages. The present study aimed to investigate the application of a water soluble oxygen sensor [Ru(dpp(SO3Na)2)3]Cl2x6H2O (RuBPS) in physiological and biochemical studies of Pectobacterium spp. and other bacteria in 96-well microplate systems. The method was optimized with respect to compound concentration, microplate type, and measurement parameters. The growth of bacteria was assessed under increased salinity, acidic and alkaline pH, decreased water availability, and osmotic stress. Utilization of various sugars by bacteria as the only carbon source and the usefulness of RuBPS in antibiotic susceptibility assays were also investigated. The studies confirmed that the respirometry assay can be successfully used to assess bacterial growth in place of the optical density measurement and the resazurin assay, or in conjugation with those methods. The assay is of special value when growth media are non-homogeneous, bacteria produce reductive compounds during growth, or when bacteria do not grow well in the medium of choice. It may be used to study adaptation potential of plant pathogenic bacteria and other bacteria, and their possible spread into new ecological niches.

Antibiotic resistance is a global problem, and one promising solution to overcome this issue is using metallodrugs, which are drugs containing metal ions and ligands. These complexes are superior to free ligands in various characteristics including anticancer properties and mechanism of action. The pharmacological potential of metallodrugs can be modulated by the appropriate selection of ligands and metal ions. A good example of proper coordination is the combination of sulfonamides (sulfamerazine, sulfathiazole) with a ruthenium(III) ion. This work aimed to confirm that the activity of sulfonamides antibacterial drugs is initiated and/or stimulated by their coordination to an Ru(III) ion. The study determined the structure, electrochemical profile, CT-DNA affinity, and antimicrobial as well as anticancer properties of the synthesized complexes. The results proved that Ru(III) complexes exhibited better biological properties than the free ligands.

Background:Analytical chemistry and biotechnology as an interdisciplinary fields of science have been developed during many years and are experiencing significant growth, to cover a wide range of microorganisms separation techniques and methods, utilized for medical therapeutic and diagnostic purposes. Currently scientific reports contribute by introducing electrophoretical and immunological methods and formation of devices applied in food protection (avoiding epidemiological diseases) and healthcare (safety ensuring in hospitals).Methods:Electrophoretic as well as nucleic-acid-based or specific immunological methods have contributed tremendously to the advance of analyses in recent three decades, particularly in relation to bacteria, viruses and fungi identifications, especially in medical in vitro diagnostics, as well as in environmental or food protection.Results:The paper presents the pathogen detection competitiveness of these methods against conventional ones, which are still too time consuming and also labor intensive. The review is presented in several parts following the current trends in improved pathogens separation and detection methods and their subsequent use in medical diagnosis.Discussion:Part one, consists of elemental knowledge about microorganisms as an introduction to their characterization: descriptions of divisions, sizes, membranes (cells) components. Second section includes the development, new technological and practical solution descriptions used in electrophoretical procedures during microbes analyses, with special attention paid to bio-samples analyses like blood, urine, lymph or wastewater. Third part covers biomolecular areas that have created a basis needed to identify the progress, limitations and challenges of nucleic-acid-based and immunological techniques discussed to emphasize the advantages of new separative techniques in selective fractionating of microorganisms.

Pyrazine‑2‑amidoxime (PAOX) is a prototypical sp2-hybridized amidoxime. Although, we described first time in details PAOX structure in solid state, the profile of PAOX behavior in aqueous solution still needs to be improved. While, acid-base properties of PAOX have been tried to define just once, the presented description was not complete and based only on the results of potentiometry during complexometric studies. The selection of method gives rise problems to observation the protonation or deprotonation processes of compound studied. Due to above, the presented studies show first time the complete description of PAOX acid-base properties by obtaining its pKa, solubility, partition (P) and distribution (D) coefficients using various methods. Among them, experiments: potentiometry; UV spectrophotometry by using Hammett's function and pH-metric titrations; cyclic voltammetry (CV) with glassy carbon electrode (GCE) and with GCE electropolymerized by poly‑ l ‑glycine (PGGCE); 1H NMR and theoretical calculations (DFT). Generally, combined four types of experimental and theoretical methods were used to estimate PAOX macro acidic-dissociation constants values. Moreover, log P and log D were determined spectrophotometrically and calculated also by DFT methods. No previous reports were found in the presented form regarding the complete drug-like properties, including negative together with positive values of pKa. Additionally, we proved by our electrochemical results that the quantitative analysis of PAOX do not need the special conditions of the electrode used in research. Hence, the comparison of our results to those described in the literature about analysis made for others, amidoxime derivatives.

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.

Two coordination compounds and their structural characterization of [Ni(PM) 2 ]Cl 2 and [Ni(PL) 2 ]Cl 2 have been studied. Pyridoxamine (PM) and pyridoxal (PL) denote individual vitamers of vitamin B 6 and both demonstrated bidentate nature inside the complexes. The acid-base behavior of the mentioned complexes and their possible interactions with biomolecules in solutions have been never reported. Here, UV-spectroscopic, potentiometric, cyclic voltammetric studies have been carried out on the interaction of the Ni(II)-vitamer complexes with protons as well as with calf thymus -DNA (CT-DNA) in aqueous medium. The acidity constants values of coordination compounds studied have been determined and compared. The potentiometric and pHmetric-spectrophotometric microtitrations were carried out at the same conditions of temperature and pH range, 25 °C and 1.72–11.68, respectively. The procedural decomposition temperatures of the complexes were given and considered in relation to the structures of the examined compounds to complete the structural description of [Ni(PM) 2 ]Cl 2 and [Ni(PL) 2 ]Cl 2 . The CT-DNA binding potential of Ni(II) complexes was carried out by absorption spectroscopy and cyclic voltammetry methods. Mechanism investigation has demonstrated that examined compounds could interact to CT-DNA by grooving binding mode, which was stabilized by hydrogen bond and van der Waals forces.

The stability of two cationic coordination polymers, {[Cu(NO3)(pm)2]}nNO3·H2O and {[Cu(Cl)(pn)2]}nNO3 (pm and pn denote pyridoxamine and pyridoxine, respectively), have been investigated in the solid state and solutions. The characterization of the solid precipitates has been acquired by X-ray, FT-IR spectroscopic, elemental analysis and thermogravimetric (27–900 °C) methods. The distorted tetragonal bipyramide geometry of a copper coordination sphere has been found in both compounds. In each case two bidentate vitamin B6 zwitterionic molecules (either pm or pn) are in equatorial positions while the axial ones are occupied by bridging ions (NO3− or Cl−). Interligand hydrogen bonds have been found to stabilize the polymers whereas the packing in crystals results from ionic interactions and charge assisted hydrogen bonding with terminal hydroxyl groups. In Cu-pm crystal lattice water molecules are also involved in the interchain H-bond network. The conductivity measurements and UV–Vis spectroscopy have confirmed the stabilization of the cationic coordination polymers in solutions. The redox properties of the compounds studied has been investigated by using cyclic voltammetry. The acid-base properties in aqueous solutions have been studied and the values of deprotonation constants have been determined by potentiometric and UV–Vis spectroscopic microtitration techniques. Finally, the application of the Cu(II)-vitamin B6 type complexes as sensing materials was proposed.

The results of the first structural studies (with the use of both experimental and theoretical methods) on pyrazine-2-amidoxime (PAOX) were shown and discussed. FT-IR spectra were recorded in different concentrations of the PAOX in apolar solvent to check the possibility of the inter- or intramolecular hydrogen-bond formation. All possible tautomers–rotamers of PAOX were then theoretically considered at the DFT(B3LYP)/6-311+G** level in vacuo. For selected isomers, calculations were also performed at higher levels of theory {B3LYP/6-311+G(3df,2p) and G3B3}. Based on the results of DFT calculations, the most stable isomers were found, and their total free energies and infrared spectra were calculated. The energy variation plots for the N8C7N9O10 and N1C2C7N9 dihedral angles were also computed to find two energy barriers, one for E/Z isomerization around the C7N9 double bond and the other one for rotation of the pyrazinyl ring around the C2C7 single bond. The results show that the stability of the PAOX isomers strongly depend on their configuration and orientation of the substituents. The possibilities of inter- and intramolecular hydrogen bonds were also experimentally and theoretically checked. Finally, a potential of mean force was determined in CHCl3 for a dimer of PAOX with hexamethylphosphoramide. Both, experimental and theoretical results are in agreement. Copyright © 2016 John Wiley & Sons, Ltd.

Pyrazine-2-thiocarboxamide ( PTCA ) was obtained after recrystallization and was characterised by elemental analysis, IR spectroscopy and thermogravimetry. Five dimers of PTCA were found in X-ray diffraction studies. These results were then compared with the known structures of a popular drug, i.e. pyrazine-2-carboxamide ( PZA ). S⋯π and π-π interactions were observed in the PTCA crystal structure as a novelty in X-ray measurements and our attention was focused on their role in stabilizing the PCTA structure. The geometry, energy and IR spectra for two conformers ( E , Z ) of PTCA and five dimers (D1-D5) were calculated for the gas phase with the DFT method at 6–311 + G(d,p) basis set. The results of calculations showed that D1 is the most stable dimer among five dimers of PTCA which were found experimentally. Thermal decomposition of PTCA was examined with the use of the TG/IR analysis (20–1000 °C) and the results were discussed. To test the antimicrobial activity of PTCA a biological assay was performed to determine its potentially pharmaceutical applications. The minimum inhibitory (MIC) and minimal bactericidal (fungicidal) concentrations (MBC) for PTCA were determined against six microorganisms.

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.

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.

Complexes of antibiotics with metal ions draw attention of scientists looking for new drugs as well as those endeavoring to increase the activity of antibiotics that are currently in use. The bioactivity of antibiotics can be increased by coordination of metal ion. Moreover, such complexes allow for reduction of drug’s dose introduced into the body and improve their bioavailability. In order to study the antimicrobial effect of antibiotics-metal complexes, it is necessary to properly determine their structure and physicochemical properties. Therefore, the selection of appropriate research methods plays a crucial role in a comprehensive understanding and prediction of metallopharmaceuticals’ activity. The electronic structure and spatial structure of antibiotic-metal complexes, their stability, ligands’ donor atoms, acid-base properties, lipophilicity and most preferable binding sites to the biomolecules are essential features of this type of compounds. This review delineates the collection of available tools and methods necessary for an exhaustive analysis of metallopharmaceuticals.

The detailed studies concerning the binding mode of bioactive ligands: pyrazine-2-carboxamide (PZA), pyrazine-2-thiocarboxamide (PTCA) and pyrazine-2-amidoxime (PAOX) have been performed by using three independent techniques: UV–Vis spectroscopy, potentiometry and conductometry. The composition and stability constants of new series Ir(III) complexes with antituberculosis drug and its structural analogues have been determined in aqueous and nonaqueous solutions. The hypsochromic shifts of bands and appearance of new peaks during UV–Vis spectrophotometric titration confirmed the interaction of Ir(III) ion with bioligands. In the studied pH range activation of pyrazine derivatives began complexation process. The sharply changed of conductimetric curves slope clearly demonstrated that the ML2 type complexes formation with relatively high stability are favored. Under the experimental conditions, it was found that metal ion interact with ligands leading to the formation of positively charged complexes. The gradual and cumulative stability constants of Ir(III) coordination compounds have been determined. The stability order of Ir(III)– PY systems studied is as follows: PAOX > PZA > PTCA. The analysis of formation equilibria revealed that mononuclear Ir(III) coordination compounds with metal to ligand molar ratio equals 1:2 are preferable with prominently high solution stability. Comparison of stability constants values showed that an increase in the efficiency of the reaction between metal ion and bioligands was observed with elongation of substituent chain. In the binary complexes, the bidentate nature of bioactive ligands and participation of amine and heterocyclic nitrogens in coordination of central ion were confirmed.

UV absorption spectra of methyl 3-azido-6-iodo-2,3,6-trideoxy-α- d - arabino -hexopyranoside were recorded over a wide pH range. On this basis, a relationship between absorbance and pH was plotted, from which deprotonation equilibrium constants of this compound were determined. Further, quantum-mechanical calculations were performed at the ab initio level both in the gas phase by using the Restricted Hartree Fock (RHF), Moller–Plesset (MP2) methods and under consideration of solvation effects within the Polarizable Continuum Model (PCM), which enabled location of preferred protonation and deprotonation centers of this compound. The results provided the basis for discussion of the influence of substituents in the sugar ring on protolytic equilibria occurring in aqueous solutions of 3-azido-2,3-dideoxy sugars.

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 pyruvate's 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 pyruvate's 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.

The acid–base properties of analogous complex ions of chromium(III) and cobalt(III) in aqueous solution have been studied. The equilibrium constants for all metal complexes were determined by using potentiometric and spectrophotometric titration methods. First, dissociation constants for the studied complexes of Cr(III) and Co(III) were determined by means of the potentiometric titration method and using the STOICHIO computer programme. Then, pH-spectrophotometric titrations were performed and the OriginPro 7.5 computer programme was used to calculate the same constants. The measurements using both methods were carried out under the same conditions of temperature, T = 298.15 K, and over the same pH range 2.00–10.00, respectively. It turned out that the two methods used enabled us to obtain acidity constants in very good agreement.