Binding Free Energy (BFE) Calculations and Quantitative Structure–Activity Relationship (QSAR) Analysis of Schistosoma mansoni Histone Deacetylase 8 (smHDAC8) Inhibitors

Histone-modifying proteins have been identified as promising targets to treat several diseases including cancer and parasitic ailments. In silico methods have been incorporated within a variety of drug discovery programs to facilitate the identification and development of novel lead compounds. In this study, we explore the binding modes of a series of benzhydroxamates derivatives developed as histone deacetylase inhibitors of Schistosoma mansoni histone deacetylase (smHDAC) using molecular docking and binding free energy (BFE) calculations. The developed docking protocol was able to correctly reproduce the experimentally established binding modes of resolved smHDAC8–inhibitor complexes. However, as has been reported in former studies, the obtained docking scores weakly correlate with the experimentally determined activity of the studied inhibitors. Thus, the obtained docking poses were refined and rescored using the Amber software. From the computed protein–inhibitor BFE, different quantitative structure–activity relationship (QSAR) models could be developed and validated using several cross-validation techniques. Some of the generated QSAR models with good correlation could explain up to ~73% variance in activity within the studied training set molecules. The best performing models were subsequently tested on an external test set of newly designed and synthesized analogs. In vitro testing showed a good correlation between the predicted and experimentally observed IC₅₀ values. Thus, the generated models can be considered as interesting tools for the identification of novel smHDAC8 inhibitors.     

Dispersion of discrete sample signals within aerosol spray chambers: preliminary investigations

A barrel-type spray chamber with a baffle system and various other structures were used for characterization of band-broadening phenomena occurring within aerosol spray chambers, with an ICP-AES detector used in this case. Absolute values of aerosol particle size distributions from nebulizer/spray chamber systems were measured and found to be affected by the relative positions of impact surfaces with respect to the nebulizer. Smaller particles, but less total mass was observed as the baffle was moved closer to the nebulizer tip. However, based on measurements herein, it does not appear that particle sizes in any case will be small enough within the spray chamber for diffusion to influence band broadening for the bulk of the aerosol mass, as particularly important for mass sensitive detectors such as ICP-AES, although diffusion is likely to be important to particle number sensitive detectors.

Dispersion within the turbulent gas-phase regions of spray chambers appears to be relatively small. Geometries which introduce stagnant gas flow regions appear to have larger effects on band-broadening. The smoke tests utilized in these studies were found to be useful aids for visualization of spray chamber flow phenomena that influence dispersion of discrete signals.

Recirculation phenomena can also play a role in band broadening. Recirculation of aerosol re-entrained into the nebulizer jet appears to have an effect on dispersion, as represented by the full width at half maximum values. On the other hand, recirculation renebulization leads to substantial peak tailing.     

Microstructure and First Hydrogenation Properties of TiHfZrNb1−xV1+x Alloy for x = 0, 0.1, 0.2, 0.4, 0.6 and 1

The effect of the substitution of Nb by V on the microstructure and hydrogen storage properties of TiHfZrNb_1−xV_1+x alloys (x = 0.1, 0.2, 0.4, 0.6 and 1) was investigated. For x = 0, the alloy was pure BCC and upon the substitution of niobium by vanadium, the BCC was progressively replaced by HCP and FCC phases. For x = 0.6, a C15 phase was also present and becomes the main phase for x = 1. The substitution greatly enhanced the first hydrogenation and makes it possible at room temperature under 20 bars of hydrogen. The capacity of all substituted alloys was around 2 wt.%.     

A lariat‐functionalized copper(II) di­imine–dioxime complex

The dimeric title copper(II) complex, diaqua‐1κO,2κO‐bis[3,9‐dimethyl‐6‐(2‐pyridyl­methyl)‐4,8‐di­aza­undeca‐3,8‐di­ene‐2,10‐dione dioximato(1?)]‐1k⁴N²,N⁴,N⁸,N¹⁰;1:2κ⁵O²:N²,N⁴,N⁸,N¹⁰‐dicopper(II) diperchlorate, [Cu₂(C₁₇H₂₄N₅O₂)₂](ClO₄)₂, crys­tallizes with one Cu atom in a square‐pyramidal environment and the other Cu atom displaying a distorted octahedral coordination. In each case, the four N atoms in the core of the ligand (two imine and two oxime N atoms) form the base of the pyramid, with a water mol­ecule at an apex. The two parts of the dimer are linked by an interaction [2.869 (2) Å] between one of the Cu atoms and one of the oxime O atoms coordinated to the second Cu atom, and also by a hydrogen bond between the apical water mol­ecule on the second Cu atom and the pyridyl N atom from the coordination sphere of the first Cu atom. The pyridyl N atoms of the lariat arms are not coordinated to either of the Cu atoms. Thus, this potentially pentadentate ligand is only tetradentate when coordinated to Cu^II.     

Hydrothermal Syntheses of NiO−GO Nanocomposite on 3D Nickel Foam as a Support for Pt Nanoparticles and its Superior Electrocatalytic Activity towards Methanol Oxidation

In this project, Pt/NiO?GO nanocatalyst is grown on nickel foam (NF) and, its catalytic activity towards electrochemical oxidation of methanol in acidic media is studied. The first step is devoted to the synthesis of NiO?GO support by a hydrothermal method. Then Pt nanoparticles (～34.3 nm) are electrodeposited on this supporting material. Hydrothermal and electrochemical deposition conditions are optimized. Surface of modified NF was inspected for physical characterization and Chemical composition by some techniques such as field emission scanning electron microscopy (FESEM), energy‐dispersive X‐ray spectra (EDS), and X‐ray diffraction (XRD). In the electrochemical section, the catalytic performance of Pt/NiO?GO/NF towards methanol oxidation is investigated by cyclic voltammetry and chronoamperometry measurements. The electrochemical impedance spectroscopy (EIS) is elected to deliberate charge transfer resistance on the catalyst surface. Mass activity, electrochemical surface area (ECSA) and durability of prepared catalysts are compared with commercial Pt/C. Deliberations prove the superiority of Pt/NiO?GO/NF towards methanol oxidation in acidic media. The Superior quality of synthesized nanocatalyst that is attributed to the synergetic effect of the NiO?GO support material and Pt nanoparticles, indicate that Pt/NiO?GO/NF can be successfully used as the anode in the direct methanol fuel cell (DMFC).     

The moment problem for continuous positive semidefinite linear functionals

Let τ be a locally convex topology on the countable dimensional polynomial ${\mathbb{R}}$ -algebra ${\mathbb{R} [\underline{X}] := \mathbb{R} [X_1, \ldots, X_{n}]}$ . Let K be a closed subset of ${\mathbb{R} ^{n}}$ , and let ${M := M_{\{g_1, \ldots, g_s\}}}$ be a finitely generated quadratic module in ${\mathbb{R} [\underline{X}]}$ . We investigate the following question: When is the cone Psd(K) (of polynomials nonnegative on K) included in the closure of M? We give an interpretation of this inclusion with respect to representing continuous linear functionals by measures. We discuss several examples; we compute the closure of ${M = \sum \mathbb{R} [\underline{X}]^{2}}$ with respect to weighted norm-p topologies. We show that this closure coincides with the cone Psd(K) where K is a certain convex compact polyhedron.     

Development of a selective fluorimetric technique for rapid trace determination of zinc using 3-hydroxyflavone

A sensitive and a selective spectrofluorimetric method have been developed for the rapid determination of trace levels of zinc. The method is based on complex formation between zinc and 3-hydroxyflavone (3HF), which displays an intense emission signal around 478 nm. The analytical performance of the method was examined by considering the factors that affect the complex formation such as pH, mole ratio of the metal and solvent type. The optimum conditions for the complex formation were metal to ligand stoichiometric ratio of 1:1 at pH 7.5 with 0.1 M Tris buffer. Under these conditions the detection limit attained was 1.5 ppb. The method was appropriately validated and yielded relative standard deviations of less than 2% (n = 5), which was considered acceptable. It was successfully applied to the trace determination of zinc in drinking water, hair shampoo and pharmaceutical samples.     

High throughput method for the analysis of cetrizine hydrochloride in pharmaceutical formulations and in biological fluids using a tris(2,2'-bipyridyl)ruthenium(II)-peroxydisulphate chemiluminescence system in a two-chip device

A fast, economic and sensitive chemiluminescence (CL) method has been developed for the analysis of cetrizine hydrochloride (CET) in pharmaceutical formulations and in biological fluids. The CL method is based on the oxidation of tris(2,2′-bipyridyl)ruthenium(II) (Ru (bipy)₃²⁺) by peroxydisulphate in a two-chip device. Up to 180 samples can be analysed per hour, consuming only minute quantities of reagents. Three instrumental setups were tested to find the most economical, sensitive and high throughput setup. In the first setup, a continuous flow of sample and CL reagents was used, whereas in the second setup, a fixed volume (2 μL) of (Ru (bipy)₃²⁺) was introduced into a continuous infusion of peroxydisulphate and the sample. In the third design, a fixed volume of sample (2 μL) was injected while the CL reagents were continuously infused. Compared to the first setup, a 200% signal enhancement was observed in the third setup. Various parameters that influence the CL signal intensity, including pH, flow rates and reagent concentrations, were optimized. A linear response was observed over the range of 50 μg L⁻¹ to 6400 μg L⁻¹ (R² = 0.9959) with RSD values of 1.1% (n = 15) for 1000 μg L⁻¹. The detection limit was found to be 15 μg L⁻¹ (S/N = 3). The amount of consumed sample was only 2 μL, from which the detected amount of CET was found to be 6.5 × 10⁻¹⁴ mol. This procedure was successfully applied to the analysis of CET in pharmaceutical formulations and biological fluids.     

Synthesis of biosourced polyether-amides from 1,4-3,6-dianhydrohexitols: Characterization by NMR and MALDI–ToF mass spectrometry

New series of polyether-amides were prepared by polycondensation in solution of three diamines based on 1,4-3,6-dianhydrohexitols with two types of diacyl chlorides (sebacoyl and isophtaloyl). Unprecedented diamines based on isomannide and isoidide were elaborated. The corresponding polyether-amides (PeA) were obtained with high yields. They were characterized by different analytical techniques (NMR, MALDI–ToF MS, DSC). The combination of MALDI–ToF MS with NMR spectroscopy allowed us to confirm structure types. DSC measurements revealed an amorphous character for the isophtaloyl family with a high T_g value. The sebacoyl series proved to be semi-crystalline with a high T_m value. Isosorbide-based PeAs demonstrated interesting properties (T_g above 210 °C and T_m above 240 °C) and high viscosity (0.32).     

Antibacterial,Antioxidant and Binding Studies of Some Novel Diaryl Sulphide Derivatives

Abstract

A series of novel acyclic and cyclic diaryl sulphides was synthesized from 2,2′-dithiobenzoic acid. The various diaryl sulphides were characterized by use of spectral (IR, ¹H and ¹³C NMR, ESI/MS) and elemental analyses. The antimicrobial activities of the compounds were evaluated in terms of their minimum inhibition concentration (MIC) against a panel of clinical isolates bacteria and were found to possess only moderate antimicrobial activities. N,N′-Bis(2-hydroxyphenyl)-2,2′-thiodibenzamide (13), exhibiting a hydroxy group at the phenyl ring, was the most active antimicrobial agent within the series, with MIC values of 0.05 mg mL^–1 and 10 mg mL^–1 against Staphylococcus aureus and Bacillus cereus, respectively. The antioxidant efficiency of the diaryl sulphides was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity with 13 being the most active compound. The interaction of 2,2′-thiodibenzanilide, N,N′-bis(2-methylphenyl)-2,2′-thiodibenzamide, and N,N′-bis(2-hydroxyphenyl)-2,2′-thiobenzamide with guanine, glutamic acid, and urea were studied quantitatively with binding constants ranging from 1 × 10³ M^?1 to 2.7 × 10⁴ M^?1.