Synthesis and Anticancer Properties of Oxazepines Related to Azaisoerianin and IsoCoQuines

In this article, we report the synthesis and biological properties of a series of novel oxazepines related to isoCA-4 having significant antitumor properties. Among them, three oxazepin-9-ol derivatives display a nanomolar or a sub-nanomolar cytotoxicity level against five human cancer cell lines (HCT116, U87, A549, MCF7, and K562). It was demonstrated that the lead compound in this series inhibits tubulin assembly with an IC₅₀ value of 1 μM and totally arrests the cellular cycle in the G2/M phase at the low concentration of 5 nM in HCT116 and K562 cells. Molecular modeling studies perfectly corroborates these promising results.     

Direct comparison of Eulerian–Eulerian and Eulerian–Lagrangian simulations for particle-laden vertical channel flow

Particle-laden flows in a vertical channel were simulated using an Eulerian–Eulerian, Anisotropic Gaussian (EE-AG) model. Two sets of cases varying the overall mass loading were done using particle sizes corresponding to either a large or small Stokes number. Primary and turbulent statistics were extracted from these results and compared with counterparts collected from Eulerian–Lagrangian (EL) simulations. The statistics collected from the small Stokes number particle cases correspond well between the two models, with the EE-AG model replicating the transition observed using the EL model from shear-induced turbulence to relaminarization to cluster-induced turbulence as the mass loading increased. The EE-AG model was able to capture the behavior of the EL simulations only at the largest particle concentrations using the large Stokes particles. This is due to the limitations involved with employing a particle-phase Eulerian model (as opposed to a Lagrangian representation) for a spatially intermittent system that has a low particle number concentration.     

Copper‐Catalyzed Trifluoromethylation of Aliphatic N‐Arylhydrazones: A Concise Synthetic Entry to 2‐Trifluoromethylindoles from Simple Aldehydes

The copper‐catalyzed C(sp²) H trifluoromethylation of N,N‐disubstituted hydrazones using the Togni reagent is demonstrated to proceed efficiently for aliphatic aldehyde‐derived substrates. The success of the reactions relied on the choice of the N,N‐diphenylamino group as the terminal hydrazone amino group where N,N‐dialkylamino groups were preferred for (hetero)aromatic aldehyde‐derived substrates. In addition, the trifluoromethylated N‐arylhydrazones are shown to be ideal substrates for Fischer indole synthesis allowing a straightforward, three‐step access to 2‐trifluoromethylindole derivatives from simple aldehydes.

     

Dielectric features of two grades of bi‐oriented isotactic polypropylene

The dielectric properties of two grades of bi‐oriented isotactic polypropylene were studied with a variety of techniques: breakdown field measurements, dielectric spectroscopy, thermally stimulated depolarization currents (Is), and direct‐current (dc) conduction I values. Standard polypropylene (STPP) and high‐crystallinity polypropylene (HCPP) films were investigated. Measurements were carried out over a wide temperature range (?150°C/+125°C). The breakdown fields in both materials showed a very small difference. On the other hand, the dielectric losses and dc conduction I values were significantly lower in HCPP. Both materials showed a decrease in the dielectric loss versus temperature in the range 20–90°C; this is favorable for application in alternating‐current power capacitors. The analysis of the dc I value allowed us to find evidence of two main conduction mechanisms: (1) below 80°C in both materials, a hopping mechanism due to the motion of electrons occurred in the amorphous phase, and (2) above 80°C, ionic conduction occurred in HCPP, and hopping conduction occurred in STPP. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42224.     

Structure and analgesic properties of layered double hydroxides intercalated with low amounts of ibuprofen

Ibuprofen‐intercalated layered double hydroxides (LDH‐IBU) have been successfully synthesized via a coprecipitation method with a nominal [Al³⁺]/[Mg²⁺] ratio of 0.5 and a variable molar IBU/([Al³⁺]+[Mg²⁺]) ratio of 0, 0.15, 0.18, 0.24, 0.36, and 0.72. After an accurate determination of the composition, the nature of the intercalated species and the effective intercalation yield from to IBU, it is shown that the synthesis route used allows a good control of the quantity of intercalated IBU within the LDH framework. This results in different samples with full or partial IBU intercalation in the interlayer space in exchange of nitrate anions. The analysis of the X‐ray diffraction basal reflections reveals that the intercalation of IBU in the framework only increases the basal distances with no alteration of the brucite‐type layers. Also, a computational study used to model the positions and shapes of the basal reflections showed that the structure of the nonfully intercalated compounds follows a random interstratification scheme. Finally, three samples ranging from slightly to fully IBU‐intercalated galleries were selected for preliminary in vivo assays. These tests showed a strong tendency that after 24 hours the low yield of IBU‐intercalated compounds are almost as efficient as the fully intercalated sample.     

The interaction between molten gallium and the hydrocarbon medium induced by ultrasonic energy—can gallium carbide be formed?

Ultrasonic irradiation of molten gallium in organic liquids (decane, dodecane, etc.) results in dispersion of the gallium into nanometric spheres. These were examined by several analytical methods XRD, DSC, Raman and IR spectroscopy) as well as electron microscopy (SEM, TEM) and found to be composed of Ga and C. The DSC analysis indicates that the Ga has possibly reacted with carbon, while the Raman spectrum of the product demonstrates a strong additional peak that could not be identified. This work explores the possibility that the product is gallium carbide or another gallium‐carbon complex. To investigate the nature of the product, we performed detailed extended X‐ray absorption fine structure (EXAFS) and X‐ray absorption near‐edge structure (XANES) analyses. On the basis of DSC, IR, and Raman it appear to be formation of GaC, whereas the analysis by EXAFS and XANES demonstrated that the gallium is found to be in a higher reduced state (almost metallic), supported by carbon. The question that remains open in addition to the one related to the formation of galium carbide is whether a complex structure, including oxygen contamination is involved in the layers surrounding the Ga as indicated by the EXAFS results.     

Influence of Microstructure and Surface Activation of Dual‐Phase Membrane Ce0.8Gd0.2O2−δ–FeCo2O4 on Oxygen Permeation

Dual‐phase oxygen transport membranes are fast‐growing research interest for application in oxyfuel combustion process. One such potential candidate is CGO‐FCO (60 wt% Ce_0.8Gd_0.2O_2?δ–40 wt% FeCo₂O₄) identified to provide good oxygen permeation flux with substantial stability in harsh atmosphere. Dense CGO‐FCO membranes of 1 mm thickness were fabricated by sintering dry pellets pressed from powders synthesized by one‐pot method (modified Pechini process) at 1200°C for 10 h. Microstructure analysis indicates presence of a third orthorhombic perovskite phase in the sintered composite. It was also identified that the spinel phase tends to form an oxygen deficient phase at the grain boundary of spinel and CGO phases. Surface exchange limitation of the membranes was overcome by La_0.6Sr_0.4Co_0.2Fe_0.8O_3?δ (LSCF) porous layer coating over the composite. The oxygen permeation flux of the CGO‐FCO screen printed with a porous layer of 10 μm thick LSCF is 0.11 mL/cm² per minute at 850°C with argon as sweep and air as feed gas at the rates of 50 and 250 mL/min.     

ASGPR‐Mediated Uptake of Multivalent Glycoconjugates for Drug Delivery in Hepatocytes

Liver cells are an essential target for drug delivery in many diseases. The hepatocytes express the asialoglycoprotein receptor (ASGPR), which promotes specific uptake by means of N‐acetylgalactosamine (GalNAc) recognition. In this work, we designed two different chemical architectures to treat Wilson's disease by intracellular copper chelation. Two glycoconjugates functionalized with three or four GalNAc units each were shown to enter hepatic cells and chelate copper. Here, we studied two series of compounds derived from these glycoconjugates to find key parameters for the targeting of human hepatocytes. Efficient cellular uptake was demonstrated by flow cytometry using HepG2 human heptic cells that express the human oligomeric ASGPR. Dissociation constants in the nanomolar range showed efficient multivalent interactions with the receptor. Both architectures were therefore concluded to be able to compete with endogeneous asialoglycoproteins and serve as good vehicles for drug delivery in hepatocytes.     

Indoloazepinone‐Constrained Oligomers as Cell‐Penetrating and Blood–Brain‐Barrier‐Permeating Compounds

Non‐cationic and amphipathic indoloazepinone‐constrained (Aia) oligomers have been synthesized as new vectors for intracellular delivery. The conformational preferences of the [l ‐Aia‐Xxx]_n oligomers were investigated by circular dichroism (CD) and NMR spectroscopy. Whereas Boc‐[l ‐Aia‐Gly]_2,4‐OBn oligomers 12 and 13 and Boc‐[l ‐Aia‐β³‐h‐l ‐Ala]_2,4‐OBn oligomers 16 and 17 were totally or partially disordered, Boc‐[l ‐Aia‐l ‐Ala]₂‐OBn ( 14 ) induced a typical turn stabilized by C₅‐ and C₇‐membered H‐bond pseudo‐cycles and aromatic interactions. Boc‐[l ‐Aia‐l ‐Ala]₄‐OBn ( 15 ) exhibited a unique structure with remarkable T‐shaped π‐stacking interactions involving the indole rings of the four l ‐Aia residues forming a dense hydrophobic cluster. All of the proposed FITC‐6‐Ahx‐[l ‐Aia‐Xxx]₄‐NH₂ oligomers 19 – 23 , with the exception of FITC‐6‐Ahx‐[l ‐Aia‐Gly]₄‐NH₂ ( 18 ), were internalized by MDA‐MB‐231 cells with higher efficiency than the positive references penetratin and Arg₈. In parallel, the compounds of this series were successfully explored in an in vitro blood–brain barrier (BBB) permeation assay. Although no passive diffusion permeability was observed for any of the tested Ac‐[l ‐Aia‐Xxx]₄‐NH₂ oligomers in the PAMPA model, Ac‐[l ‐Aia‐l ‐Arg]₄‐NH₂ ( 26 ) showed significant permeation in the in vitro cell‐based human model of the BBB, suggesting an active mechanism of cell penetration.     

CFD as an approach to understand flammable dust 20 L standard test: Effect of the ignition time on the fluid flow

A computational study based on the Euler–Lagrange approach was developed for the characterization of flammable dusts in the 20 L sphere standard test. The aim of the study was to analyze some parameters that might affect the experimental data (e.g., cold turbulence and particle size). The turbulence of a wheat starch cloud was described with the Detached Eddy Simulation model. Both the pressure of the system and the RMS velocity were compared with the flow patterns established with a particle image velocimetry analysis. It was concluded that the rebound nozzle forms a cloud that is composed by clumps. This fact implies dissimilarities between the local concentrations and the nominal value. Finally, a granulometric analysis established that the mean diameter of the particle size distribution (PSD) decreased by 69% during the dispersion. Thus, it is suggested to consider the PSD at the ignition zone rather than the PSD of the sample. © 2017 American Institute of Chemical Engineers AIChE J, 63: 42–54, 2018