Gregoryehlers9006

Isoniazid is an important first-line antitubercular drug used in the treatment of all major clinical manifestations of tuberculosis, including both pulmonary and cerebral diseases. However, it is associated with significant drawbacks due to its inherent hydrophilic nature, including poor gut permeability and an inability to cross the lipophilic blood-brain barrier, which, in turn, limit its clinical efficacy. We hypothesized that the addition of a hydrophobic moiety to this molecule would help overcome these limitations and improve its bioavailability in the bloodstream. Therefore, we designed a stable, covalently linked lipid-drug conjugate of isoniazid with a short lipid chain of stearoyl chloride. Further, lipid-drug conjugate nanoparticles were synthesized from the bulk lipid-drug conjugate by a cold high-pressure homogenization method enabled by the optimized use of aqueous surfactants. The nanoparticle formulation was characterized systematically using in vitro physicochemical analytical methods, includ by progressive intracellular trafficking into endosomal and lysosomal vesicles and colocalization with intravesicular compartmental proteins associated with mycobacterium tuberculosis pathogenesis, including CD63, LAMP-2, EEA1, and Rab11. The developed lipid-drug conjugate nanoparticles, therefore, displayed significant ability to improve the intracellular delivery of a highly water-soluble drug such as isoniazid. Copyright © 2020 American Chemical Society.A spectrophotometric technique has been applied for studying the reduction of chromium(VI) by poly(ethylene glycol) (PEG) as water-soluble and nontoxic synthetic polymer at a constant ionic strength of 4.0 mol dm-3 in the absence and presence of the ruthenium(III) catalyst. In the absence of the catalyst, the reaction orders in [Cr(VI)] and [PEG] were found to be unity and fractional first orders, respectively. The oxidation process was found to be acid-catalyzed with fractional second order in [H+]. The addition of Ru(III) was found to catalyze the oxidation rates with observation of zero-order reaction in [CrO4 2-] and fractional orders in both [PEG] and [Ru(III)], respectively. The PEG reduces the soluble toxic hexavalent Cr(VI) as a model pollutant to the insoluble nontoxic Cr(III) complex, which is known to be eco-friendly and more safer from the environmental points of view. The acid derivative of PEG was found to possess high affinity for the removal of poisonous heavy metal ions from contaminant matters by chelation. Formation of the 11 intermediate complex has been kinetically revealed. A consistent reaction mechanism of oxidation was postulated and discussed. Copyright © 2020 American Chemical Society.Tetrazolium violet (TZV) is an important pharmaceutical intermediate for the preparation of various medicines, taking into account microbiological studies and TZV as a new inhibitor of heterocyclic compound. The corrosion inhibiting action of TZV for copper in 0.5 M H2SO4 solutions was assessed by potentiodynamic polarization and electrochemical impedance spectroscopy. The corroded copper surfaces were evaluated by scanning electron microscopy. Thereafter, the thermodynamics of TZV adsorption onto copper was computed and evaluated. As a result, the target TZV compound shows great corrosion inhibition performance to protect copper in sulfuric acid. Thermodynamic test results reveal that the Langmuir, Dhar-Flory-Huggins, and Bockris-Swinkels isotherm models provide a better description for the adsorption process of TZV on the metal surface. The calculated values of ΔG ads 0 indicate a spontaneous adsorption process of TZV on the copper surface accompanied by two kinds of interactions, physical adsorption and chemisorption. Copyright © 2020 American Chemical Society.Poly(aspartic acid) (PAA) is a biodegradable water-soluble anionic polymer that can potentially replace poly(acrylic acid) for industrial applications and has shown promise for regenerative medicine and drug delivery. This paper describes an efficient and sustainable route that uses protease catalysis to convert l-aspartate diethyl ester (Et2-Asp) to oligo(β-ethyl-α-aspartate), oligo(β-Et-α-Asp). Comparative studies of protease activity for oligo(β-Et-α-Asp) synthesis revealed α-chymotrypsin to be the most efficient. Papain, which is highly active for l-glutamic acid diethyl ester (Et2-Glu) oligomerization, is inactive for Et2-Asp oligomerization. The assignment of α-linkages between aspartate repeat units formed by α-chymotrypsin catalysis is based on nuclear magnetic resonance (NMR) trifluoacetic acid titration, circular dichroism, and NMR structural analysis. The influence of reaction conditions (pH, temperature, reaction time, and buffer/monomer/α-chymotrypsin concentrations) on oligopeptide yield and average degree of polymerization (DPavg) was determined. Under preferred reaction conditions (pH 8.5, 40 °C, 0.5 M Et2-Asp, 3 mg/mL α-chymotrypsin), Et2-Asp oligomerizations reached maximum oligo(β-Et-α-Asp) yields of ∼60% with a DPavg of ∼12 (M n 1762) in just 5 min. Computational modeling using Rosetta software gave relative energies of substrate docking to papain and α-chymotrypsin active sites. The substrate preference calculated by Rosetta modeling of α-chymotrypsin and papain for Et2-Asp and Et2-Glu oligomerizations, respectively, is consistent with experimental results. Copyright © 2020 American Chemical Society.Formaldehyde is a volatile organic compound (VOC) with extensive applications, volatility, and toxicity, which have made it an important risk to human health even at low concentrations. Therefore, rapid detection of formaldehyde vapors in the environment is a necessity. Bcl-2 inhibitor Herein, we introduce a resistive gas sensor based on zeolitic imidazolate framework-8/multiwalled carbon nanotube (ZIF-8/MWCNT) for detection of formaldehyde vapors at room temperature. In this sensor, a low amount of MWCNTs was used in order to improve the electrical conductivity of the porous nanoparticles of ZIF-8. The sensor was fabricated by deposition of a thin layer of the nanocomposite onto interdigitated electrodes, and its sensing ability was investigated on exposure to formaldehyde vapors. The obtained sensor showed sensitive and fast responses to different concentrations of formaldehyde, and the sensor response to formaldehyde was higher than toward some other VOCs, including methanol, ethanol, acetone, and acetonitrile. Furthermore, because of the hydrophobic nature of ZIF-8, the effect of relative humidity on the gas-sensing performance was insignificant, which proves that this sensor is suitable for use under humid conditions.