Fullerene quinazolinone conjugates targeting Mycobacterium tuberculosis: a combined molecular docking,QSAR, and ONIOM approach

Fullerene and its derivatives may bind to biological molecules, causing inhibitory effects. In this context, investigations of interactions of fullerene-based conjugates with proteins are of general interest. Particularly, fullerene and its derivatives demonstrate antibacterial properties; and one of the potential targets for drug design and health therapy is the inhibition of 6-oxopurine phosphoribosyltransferase in Mycobacterium tuberculosis (PDB code: 4RHY). In this article, the binding interactions between a series of quinazoline-4(3H)-ones and their fullerene derivatives with the target transferase were computationally investigated. Initially, we developed predictive quantitative structure-activity relationships (QSAR) models. Next, we introduced a simplified calculation schema that allows to evaluate relative binding affinities and to reveal specific mechanisms of action. For this purpose, the molecular docking approach was utilized to identify the native poses of the 18 transferase inhibitors. The binding pocket of the target protein was isolated and semi-empirical, and hybrid ONIOM scoring functions at different levels of theory were used to treat the ligands and the isolated binding pocket. The agreement within the calculated binding-free energies trends, as well as the agreement with the experimental data, suggests that the developed calculation schema can be used to estimate relative binding affinities towards 4RH. The combination of quantum-chemical models and QSAR models could be applied for future design of new selective inhibitors.     

A Comparison of Tissue Spray and Lipid Extract Direct Injection Electrospray Ionization Mass Spectrometry for the Differentiation of Eutopic and Ectopic Endometrial Tissues

Recent research revealed that tissue spray mass spectrometry enables rapid molecular profiling of biological tissues, which is of great importance for the search of disease biomarkers as well as for online surgery control. However, the payback for the high speed of analysis in tissue spray analysis is the generally lower chemical sensitivity compared with the traditional approach based on the offline chemical extraction and electrospray ionization mass spectrometry detection. In this study, high resolution mass spectrometry analysis of endometrium tissues of different localizations obtained using direct tissue spray mass spectrometry in positive ion mode is compared with the results of electrospray ionization analysis of lipid extracts. Identified features in both cases belong to three lipid classes: phosphatidylcholines, phosphoethanolamines, and sphingomyelins. Lipids coverage is validated by hydrophilic interaction liquid chromatography with mass spectrometry of lipid extracts. Multivariate analysis of data from both methods reveals satisfactory differentiation of eutopic and ectopic endometrium tissues. Overall, our results indicate that the chemical information provided by tissue spray ionization is sufficient to allow differentiation of endometrial tissues by localization with similar reliability but higher speed than in the traditional approach relying on offline extraction.

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Ozonolysis of 18α-Oleanane triterpenoid with an alkenenitrile moiety in the five-membered ring A

A novel synthetic protocol of ozonolytic cleavage of 18α-oleanane triterpenoid with the five-membered α,β-alkenenitrile moiety dissolved in dichloromethane to selectively synthesize a 1,3-secotriterpene derivative with 78% yield was developed. Spontaneous condensations of the synthesized 19β,28-epoxy-1,3-seco-2-nor-18α-olean-3-al-1-oic acid followed by formation of unsubstituted 1,3- and 1,4-lactones were registered in reactions with sodium borohydride as a reducing reagent or oxalyl chloride as an activating agent, respectively. α-Methoxy- and α-ethoxy-substituted 1,3-lactones were obtained when the polar protic solvents methanol or ethanol were used for the ozonolysis of the alkenenitrile. Experiments on ozonolysis were carried out in combination with reduction with dimethyl sulfide. Ozonolysis of alkenenitrile in dichloromethane without reductive treatment was found out to have resulted in stable triterpene ozonide.     

Thermal stability of Friedel’s salt from metakaolin origin by DSC and HTXRD techniques

Journal of Thermal Analysis and Calorimetry - The structural relaxation of Na2O–K2O–CaO–ZrO2–SiO2 (NKCZ), Na2O–K2O–ZnO–ZrO2–SiO2 (NKzZ),...     

The role of cardiac tissue structure in defibrillation

The purpose of this paper is to investigate the relationship between cardiac tissue structure, applied electric field, and the transmembrane potential induced in the process of defibrillation. It outlines a general understanding of the structural mechanisms that contribute to the outcome of a defibrillation shock. Electric shocks defibrillate by changing the transmembrane potential throughout the myocardium. In this process first and foremost the shock current must access the bulk of myocardial mass. The exogenous current traverses the myocardium along convoluted intracellular and extracellular pathways channeled by the tissue structure. Since individual fibers follow curved pathways in the heart, and the fiber direction rotates across the ventricular wall, the applied current perpetually engages in redistribution between the intra- and extracellular domains. This redistribution results in changes in transmembrane potential (membrane polarization): regions of membrane hyper- and depolarization of extent larger than a single cell are induced in the myocardium by the defibrillation shock. Tissue inhomogeneities also contribute to local membrane polarization in the myocardium which is superimposed over the large-scale polarization associated with the fibrous organization of the myocardium. The paper presents simulation results that illustrate various mechanisms by which cardiac tissue structure assists the changes in transmembrane potential throughout the myocardium. (c) 1998 American Institute of Physics.     

The structure of a thiadiazole-containing expanded heteroazaporphyrinoid determined by gas electron diffraction and density functional theory calculations

The molecular structure of a macrocycle with a 24-membered ring, a thiadiazole-containing expanded heteroazaporphyrinoid, has been, for the first time, directly characterised by a synchronous gas electron diffraction and mass spectrometric experiment and DFT calculations; the molecule has the equilibrium structure of C(3h) symmetry with a planar macrocycle.     

ESR‐Vis/NIR Spectroelectrochemical Study of C70(CF3)2−. and C70(C2F5)2−. Radical Anions

A spectroelectrochemical study of the two isostructural asymmetric perfluoroalkyl derivatives C₁‐7,24‐C₇₀(CF₃)₂ and C₁‐7,24‐C₇₀(C₂F₅)₂ is presented. Reversible formation of their stable monoanion radicals is monitored by cyclic voltammetry and by in situ ESR‐Vis‐NIR spectroelectrochemistry. The ESR spectrum of the C₇₀(CF₃)₂^?. radical is a 1:3:3:1 quartet with a ¹⁹F hyperfine coupling constant (a(F)) of 0.323(4) G, demonstrating that the unpaired spin is coupled to only one of the two CF₃ groups. The ¹³C satellites are assigned to specific carbon atoms. The ESR spectrum of the C₇₀(C₂F₅)₂^?. radical is an apparent octet with an apparent a(F) value of 0.83(2) G. DFT calculations suggest that this pattern is due to the superposition of spectra for four nearly isoenergetic C₇₀(C₂F₅)₂^?. conformers. Time‐dependent DFT calculations suggest that the NIR band at 1090 nm exhibited by both C₇₀(R_f)₂^?. radical anions is assigned to the SOMO→LUMO+3 transition. The analogous NIR band exhibited by the closed‐shell C₇₀(CF₃)₂^2? dianion was blue‐shifted to 1000 nm.     

Gel-based immunoassay for non-instrumental detection of pyrene in water samples

A new qualitative immunologically based tube test for non-instrumental detection of pyrene (PYR) in water samples was developed. The method combines the pre-concentration of analyte by immunoextraction and its detection by immunoassay using Sepharose 4B-immobilized IgG-fraction of a polyclonal anti-PYR antiserum (immunoaffinity gel) and 1-pyrenebutyric acid-horseradish peroxidase conjugate (PYR-BA-HRP). The immunoaffinity gel was placed in a standard 1-ml SPE column through which a 10-ml aliquot of water sample spiked with 10% acetonitrile was passed. Following, free antibody binding sites were detected by application of PYR-BA-HRP. Four minutes after addition of the chromogenic substrate the results were visually evaluated by occurring or stayed away blue colour development for negative and positive samples, respectively. Total time for assay was about 15 min for six samples. Under optimized conditions a cut-off level for pyrene of 0.04 ng ml(-1) was found. At this defined concentration, a set of spiked samples (n=175) was analyzed and very low rates of false negatives (1.2%) and false positives (4.6%) determined which fulfils the requirement set by Commission Decision 2002/657/EC for a screening method. No interference by other PAH compounds like naphthalene, fluoranthene, phenanthrene, anthracene, and benzo[a]pyrene at a concentration of 20 ng ml(-1), i.e., 500-fold excess compared to the defined cut-off level was observed. Different water types like surface water, tap water, bottled water, and melted snow were analyzed for PYR contamination by the proposed method and results confirmed by HPLC-FLD.     

Electrochemical determination of chromium(VI) using metallic nanoparticle-modified carbon screen-printed electrodes

Carbon screen-printed electrodes (CSPEs) modified with metal nanoparticles present an interesting alternative in the determination of chromium(VI) by differential pulse voltammetry (DPV).Metallic silver and gold nanoparticle deposits have been obtained by electrochemical deposition. Scanning electron microscopy measurements show that the electrochemically synthesized silver and gold nanoparticles are deposited in aggregated form.The detection limit for the analytical procedures developed in this work were 8.5 × 10⁻⁷ and 4.0 × 10⁻⁷ M for silver and gold nanoparticle-modifed CSPE, respectively.In terms of reproducibility, the precision of the above-mentioned method was calculated at 6.7% in %R.S.D. values for silver and 3.21% for gold nanoparticle CSPE.     

Comparison of stir bar sorptive extraction and membrane-assisted solvent extraction for the ultra-performance liquid chromatographic determination of oxazole fungicide residues in wines and juices

The present study compares two new sample preparation methods, stir bar sorptive extraction (SBSE) and membrane-assisted solvent extraction (MASE) coupled to the novel technique of ultra-performance liquid chromatography (UPLC) for the sensitive, selective and solvent-free determination of six oxazole fungicide residues (hymexazol, drazoxolon, vinclozolin, chlozolinate, oxadixyl and famoxadone) in wine and juices. The analytes were separated on a rapid resolution C(18) column (50 mm x 4.6 mm, I.D., 1.8 microm) thermostated at 50 degrees C with isocratic elution using a 50/50 (v/v) water/acetonitrile (ACN) mobile phase at a flow-rate of 1 mL min(-1) and detected by diode-array detection (DAD). The UPLC method rapidly separates the fungicides (7 min). The best results as regards sensitivity, repeatability and analyte recovery were obtained using SBSE with a polydimethylsiloxane (PDMS) twister, at 60 degrees C for 30 min with stirring at 1700 rpm in the presence of a 0.1M acetate/acetic acid buffer (pH 5) and 20% (m/v) sodium chloride. Liquid desorption was performed with 100 microL of a 80/20 (v/v) ACN/water solution in a desorption time of 15 min. With the PDMS polymer, an apolar phase, hymexazol and oxadixyl were not extracted. Consequently, the SBSE procedure can only be applied to the other four fungicides. Detection limits ranged from 0.05 to 2.5 microgL(-1) at a signal to noise ratio of 3, depending on the compound. Recoveries obtained for spiked samples were satisfactory (83-113%) for all compounds. The proposed method was successfully applied to the analysis of different samples, residues of chlozolinate and drazoxolon being found in samples of red wine and grape juice, respectively.