Carbon Paste Electrode for the Potentiometric Flow Injection Analysis of Drotaverine Hydrochloride in Serum and Urine

A carbon paste electrode for drotaverine hydrochloride (DvCl) was prepared and fully characterized in terms of composition, life span, usable pH range, response time and temperature. The electrode was applied to the potentiometric determination of drotaverinium ions in pharmaceutical preparations and biological fluids in steady state and flow injection conditions (FIA). The electrode is based on a mixture of two ion exchangers, namely, drotaverinium-silicotungestate and drotaverinium-tetraphenylborate dissolved in tricresyl phosphate as pasting liquid. The modified electrode showed a near-Nernstian slope of 59.34±2mV over the concentration range of 5.0×10^–7–1.0 × 10^–2M. The electrode exhibits good selectivity for DvCl with respect to a large number of inorganic cations, organic cations, sugars and amino acids. Potentiometric titrations of DvCl with several titrants have been monitored using this modified carbon paste electrode as an end-point indicator electrode. The proposed electrode offers the advantages of simplicity, accuracy, automation feasibility and applicability to turbid and colored samples.     

Design,Synthesis, Docking,DFT, MD Simulation Studies of a New Nicotinamide-Based Derivative: In Vitro Anticancer and VEGFR-2 Inhibitory Effects

A nicotinamide-based derivative was designed as an antiproliferative VEGFR-2 inhibitor with the key pharmacophoric features needed to interact with the VEGFR-2 catalytic pocket. The ability of the designed congener ((E)-N-(4-(1-(2-(4-benzamidobenzoyl)hydrazono)ethyl)phenyl)nicotinamide), compound 10, to bind with the VEGFR-2 enzyme was demonstrated by molecular docking studies. Furthermore, six various MD simulations studies established the excellent binding of compound 10 with VEGFR-2 over 100 ns, exhibiting optimum dynamics. MM-GBSA confirmed the proper binding with a total exact binding energy of −38.36 Kcal/Mol. MM-GBSA studies also revealed the crucial amino acids in the binding through the free binding energy decomposition and declared the interactions variation of compound 10 inside VEGFR-2 via the Protein–Ligand Interaction Profiler (PLIP). Being new, its molecular structure was optimized by DFT. The DFT studies also confirmed the binding mode of compound 10 with the VEGFR-2. ADMET (in silico) profiling indicated the examined compound’s acceptable range of drug-likeness. The designed compound was synthesized through the condensation of N-(4-(hydrazinecarbonyl)phenyl)benzamide with N-(4-acetylphenyl)nicotinamide, where the carbonyl group has been replaced by an imine group. The in-vitro studies were consonant with the obtained in silico results as compound 10 prohibited VEGFR-2 with an IC₅₀ value of 51 nM. Compound 10 also showed antiproliferative effects against MCF-7 and HCT 116 cancer cell lines with IC₅₀ values of 8.25 and 6.48 μM, revealing magnificent selectivity indexes of 12.89 and 16.41, respectively.     

Eosin photodegradation over TiO2 modified by γ-ray irradiation

TiO₂ thin films are elaborated by sol gel on glass substrates and irradiated with ⁶⁰Co γ-rays. The X-ray diffraction, UV-Visible spectroscopy and transport properties are investigated. The films are nominally non stochiometric and the conductivity occurs by thermally activated hopping of lattice polaron. The oxygen vacancies induced by γ-ray irradiation at lower dose (<10 kGy) generate mixed valences Ti⁴⁺/³⁺, thus altering the transport properties. The photo-electrochemical characterisation is undertaken to evaluate the photo catalytic performance. The Mott-Schottky plots are characteristic of n type conduction from which a flat band potential of ?0.62 V _SCE and a donor density of 5 × 10¹⁷ cm^?3 are determined for the most active film. The Nyquist plot exhibits a semi-circular arc whose center lies below the real axis, due to the constant phase element (CPE). The energy band diagram shows the potentiality of the films for the eosin photodegradation. 68% of initial concentration (10 mg L^?1) disappears after 2 h of exposure to the solar light. TiO₂ irradiated with gamma dose of 10 kGy shows the best efficiency, due to the resistance decrees and high electron mobility (25 cm² V^?1 s^?1). The eosin oxidation follows a first order kinetic with a rate constant of 6 × 10^?2 min^?1.     

Magnetic Polymer Composite Particles Via In situ Inverse Miniemulsion Polymerization Process

We aimed at preparing magnetic iron oxide particles by the oxidation-precipitation method in order to encapsulate these particles in polymer matrices composed of poly(acrylamide-styrene sulfonic acid sodium salt). Nanocomposites were synthesized by the incorporation of surface treated magnetic nanoparticles in the synthesized polymers via in situ inverse mini-emulsion polymerization process. The study parameter was the ionic monomer content in the synthesized polymers. The structure and the morphology of the magnetic nanogels were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), dynamic light scattering (DLS), thermal gravimetric analysis (TGA) and scanning electron microscopy (SEM). FTIR and XRD showed that pure magnetite was formed and successfully encapsulated in the composite nanoparticles. The polymer encapsulation could reduce the susceptibility to leaching and could protect the magnetite particle surfaces from oxidation. The ionic monomer content had a great effect on the magnetization behavior. Magnetite prepared by the oxidation precipitation method, of 50 nm mean particle size, was embedded successfully into the polymer nanogels with a reasonable magnetic response, as proved by vibrating sample magnetometer measurement. Magnetic nanocomposites were proven to be super-ferromagnetic materials.     

Antileukemic α-pyrone derivatives from the endophytic fungus Alternaria phragmospora

Four new (1–4) and two known (5 and 6) α-pyrone derivatives have been isolated from Alternaria phragmospora, an endophytic fungus from Vinca rosea, leaves. The isolated compounds were chemically identified to be 5-butyl-4-methoxy-6-methyl-2H-pyran-2-one (1), 5-butyl-6-(hydroxymethyl)-4-methoxy-2H-pyran-2-one (2), 5-(1-hydroxybutyl)-4-methoxy-6-methyl-2H-pyran-2-one (3), 4-methoxy-6-methyl-5-(3-oxobutyl)-2H-pyran-2-one (4), 5-(2-hydroxyethyl)-4-methoxy-6-methyl-2H-pyran-2-one (5), and 5-[(2E)-but-2-en-1-yl]-4-methoxy-6-methyl-2H-pyran-2-one (6). Compounds 2 and 4 showed moderate antileukemic activities against HL60 cells with IC₅₀ values of 2.2 and 0.9 μM and against K562 cells with IC₅₀ values of 4.5 and 1.5 μM, respectively.     

Molecular Cage Assembly by Sn−O−Sn Bridging of Di-, Tri- and Tetranuclear Organotin Tectons: Extending the Spacing in Double Ladder Structures

Hydrolysis reactions of di- and trinuclear organotin halides yielded large novel cage compounds containing Sn−O−Sn bridges. The molecular structures of two octanuclear tetraorganodistannoxanes showing double-ladder motifs, viz., [{Me₃SiCH₂(Cl)SnCH₂YCH₂Sn(OH)CH₂SiMe₃}₂(μ-O)₂]₂ [ 1 , Y=p-(Me)₂SiC₆H₄-C₆H₄Si(Me)₂] and [{Me₃SiCH₂(I)SnCH₂YCH₂Sn(OH)CH₂SiMe₃}₂(μ-O)₂]₂ ⋅ 0.48 I₂ [ 2⋅ 0.48 I₂, Y=p-(Me)₂SiC₆H₄-C₆H₄Si(Me)₂], and the hexanuclear cage-compound 1,3,6-C₆H₃(p-C₆H₄Si(Me)₂CH₂Sn(R)₂OSn(R)₂CH₂Si(Me)₂C₆H₄-p)₃C₆H₃-1,3,6 ( 3 , R=CH₂SiMe₃) are reported. Of these, the co-crystal 2⋅ 0.48 I₂ exhibits the largest spacing of 16.7 Å reported to date for distannoxane-based double ladders. DFT calculations for the hexanuclear cage and a related octanuclear congener accompany the experimental work.     

2-Hydroxyestradiol Overcomes Mesenchymal Stem Cells-Mediated Platinum Chemoresistance in Ovarian Cancer Cells in an ERK-Independent Fashion

Ovarian cancer (OC) is the second most common type of gynecological malignancy. Platinum (Pt)-based chemotherapy is the standard of care for OC, but toxicity and acquired chemoresistance has proven challenging. Recently, we reported that sensitivity to platinum was significantly reduced in a co-culture of OC cells with MSC. To discover compounds capable of restoring platinum sensitivity, we screened a number of candidates and monitored ability to induce PARP cleavage. Moreover, we monitored platinum uptake and expression of ABC transporters in OC cells. Our results showed that 2-hydroxyestradiol (2HE2), a metabolite of estradiol, and dasatinib, an Abl/Src kinase inhibitor, were significantly effective in overcoming MSC-mediated platinum drug resistance. Dasatinib activity was dependent on ERK1/2 activation, whereas 2HE2 was independent of the activation of ERK1/2. MSC-mediated platinum drug resistance was accompanied by reduced intracellular platinum concentrations in OC cells. Moreover, MSC co-cultured with OC cells resulted in downregulation of the expression of cellular transporters required for platinum uptake and efflux. Exposure to 2HE2 and other modulators resulted in an increase in intracellular platinum concentrations. Thus, 2HE2 and dasatinib might act as sensitizers to restore platinum drug sensitivity to OC cells and thus to limit TME-mediated chemoresistance in OC.     

A matrix formulation for the dynamic analysis of planar mechanisms using point coordinates and velocity transformation

This paper presents a matrix formulation for the dynamic analysis of planar mechanisms consisting of interconnected rigid bodies. The formulation initially uses the rectangular Cartesian coordinates of an equivalent constrained system of particles to define the configuration of the mechanical system. This results in a simple and straightforward procedure for generating the equations of motion. The equations of motion are then derived in terms of relative joint coordinates through the use of a velocity transformation matrix. The velocity transformation matrix relates the relative joint velocities to the Cartesian velocities. For the open-loop case, this process automatically eliminates all of the non-working constraint forces and leads to an efficient integration of the equations of motion. For the closed-loop case, suitable joints should be cut and few cut-joints constraint equations should be included for each closed loop. Two examples are used to demonstrate the generality and efficiency of the proposed method.     

Structure and stability characteristics of turbulent planar flames with inhomogeneous jet in a concentric flow slot burner

Turbulent flames with compositionally inhomogeneous mixtures are common in many combustion systems. Turbulent jet flames with a circular nozzle burner were used earlier to study the impact of inhomogeneous mixtures, and these studies showed that the nozzle radius affects the flame stability. Accordingly, planar turbulent flames with inhomogeneous turbulent jet are created in a concentric flow slot burner (CFSB) to avoid this effect in the present study. The stability characteristics, the mixing field structure, and the flame front structure were measured, and the correlations between stability and the mixing field structure were investigated. The mixture fraction field was measured in non-reacting jets at the nozzle exit using highly resolved Rayleigh scattering technique, and the flame front was measured in some selected turbulent flames using high-speed Planar Laser-Induced Fluorescence (PLIF) of OH technique. The data show strong correlations between flame stability and the range of mixture fraction fluctuations. The flames are highly stabilized within a mixing field environment with the range of fluctuation in mixture fraction close to the range of the flammability limits. The mixing field structure is also illustrated and discussed using a mixing regime diagram and showed that the scatter of the data of the different cases is consistent with the classified mixing regimes. Lean flames are stabilized in the current slot burner. The flame front structure topology varies consistently from thin, small curvature at the low level of turbulence and higher equivalence ratio to more wrinkled, larger curvature, but a thicker structure at a higher level of turbulence and lower equivalence ratio.