Structure–Activity Relationships of Benzenesulfonamide‐Based Inhibitors towards Carbonic Anhydrase Isoform Specificity

Carbonic anhydrases (CAs) are implicated in a wide range of diseases, including the upregulation of isoforms CA IX and XII in many aggressive cancers. However, effective inhibition of disease‐implicated CAs should minimally affect the ubiquitously expressed isoforms, including CA I and II, to improve directed distribution of the inhibitors to the cancer‐associated isoforms and reduce side effects. Four benzenesulfonamide‐based inhibitors were synthesized by using the tail approach and displayed nanomolar affinities for several CA isoforms. The crystal structures of the inhibitors bound to a CA IX mimic and CA II are presented. Further in silico modeling was performed with the inhibitors docked into CA I and XII to identify residues that contributed to or hindered their binding interactions. These structural studies demonstrated that active‐site residues lining the hydrophobic pocket, especially positions 92 and 131, dictate the positional binding and affinity of inhibitors, whereas the tail groups modulate CA isoform specificity. Geometry optimizations were performed on each ligand in the crystal structures and showed that the energetic penalties of the inhibitor conformations were negligible compared to the gains from active‐site interactions. These studies further our understanding of obtaining isoform specificity when designing small molecule CA inhibitors.     

Inner surface modification of halloysite nanotubes and its influence on morphology and thermal properties of polystyrene/polyamide‐11 blends

The asymmetry of halloysite surface chemistry was used to perform a selective modification of its inner surface via grafting of a synthesized styrene/(methacryloyloxy)methyl phosphonic acid copolymer. Fourier transform infrared spectroscopy, thermogravimetric analysis (TGA) and pyrolysis gas chromatography/mass spectrometry were used to evidence and quantify the grafting. Then, raw and hybrid nanoparticles were incorporated in polystyrene (PS)/polyamide‐11 (PA11) blends (80/20 and 60/40 wt%). Scanning electron micrographs showed differences in localization of the halloysite nanotubes (HNTs), since raw halloysite is concentrated in the PA11 phase while modified halloysite is also located at the PS/PA11 interface, leading to a better interfacial adhesion between PS and PA11. An inhibiting effect of modified halloysite on PA11 coalescence was evidenced by measuring the particle size distribution of the extracted nodules. Moreover, the presence of modified halloysite at the interface shows an improvement in terms of thermal stability as observed by TGA, but with no significant effects on PA11 crystallization behaviour as shown by differential scanning calorimetry results. Rheological measurements were carried out to study the influence of the surface modification of halloysite on the blend morphology. A gel‐like behaviour was observed for the (60/40 wt%) HNTs reinforced composition that was enhanced in the case of 10% functionalized halloysite. © 2016 Society of Chemical Industry     

Crystallinity and mechanical properties of polylactide/ether‐amide copolymer blends

The present study focuses on the improvement of impact properties and particularly on the interaction between crystallinity development and mechanical properties of impact modified polylactide (PLA). The PLA was toughened by the addition of a random linear ether‐amide copolymer (PEBAX 3533?). A random copolymer of ethylene, methyl‐acrylate, and glycidyl‐methacrylate (LOTADER AX8900?) was also used to reactively compatibilize the ether‐amide copolymer with the PLA matrix. Melt rheology of the blends was investigated in small amplitude oscillatory shear and showed that the impact modifier could significantly influence the viscoelastic response of the material. The Izod impact resistance and tensile properties were measured using standard testing protocols. The blend morphology was also examined using scanning electron microscopy on cryofractured and microtomed surfaces, while the crystalline morphology was assessed by optical microscopy. A sub‐micron dispersion of the impact modifier was achieved in the presence of the reactive compatibilizer. Significantly improved impact strength was found with 10 wt % impact modifier. High crystallinity samples showed the highest impact strength with values reaching 68 kJ/m², hence a 20‐fold improvement with respect to the neat PLA. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134 , 44677.     

Consolidation by spark plasma sintering (SPS) of polyetheretherketone

The present study deals with the consolidation of an ultra‐high performance polymer, the poly(ether ether ketone) (PEEK), for structural applications, using the powder metallurgy (PM) way, and more precisely the Spark Plasma Sintering (SPS) processing. The effects of SPS parameters such as temperature, pressure, and dwell time on density and mechanical properties of PEEK were investigated via a Design of Experiments (DoE). A temperature of 250 °C, a pressure of 40 MPa, and a dwell time of 20 min have been identified as the optimal SPS process parameters. In these conditions, a density of 1.31 g / cm³ was reached and homogeneous mechanical properties in the volume determined by means of compression tests were found with a compressive modulus of 2.75 GPa, a yield strength of 134 MPa, and a maximum compressive strain of 43%. These results are better than those of commercial products obtained by injection molding. The pressure appears to be a significant parameter on PEEK properties and plays positive or negative roles according to the responses of DoE studied. To our knowledge, it is one of the first studies based on the application of the PM techniques for PEEK consolidation showing the possibility to process below its melting point. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44911.     

Investigation of the collapse of bubbles after the impact of a piston on a liquid free surface

A novel technique based on the impact of a piston on a liquid confined in a vessel is described. Pressure measurements reveal that strong pressure variations (up to 100 atmospheres) with a rich content of frequencies are efficiently transmitted to the liquid. High‐speed camera visualizations show that pre‐existing millimetric bubbles always collapse during the first instants of the impact whereas the behavior of submillimetric bubbles depends on the features of the pressure evolution in the system. In addition to the impact velocity, the amount of gas/vapor trapped between the piston and the liquid's surface plays an important role on how pressure evolves. Only when negative pressure occurs tiny bubbles grow significantly and collapse. The violent collapse of bubbles promote turbulence and mixing at very small length‐scales which renders this technique interesting to intensify processes limited by heat and mass diffusion. © 2017 American Institute of Chemical Engineers AIChE J, 63: 2483–2495, 2017     

Structure and properties of clay ceramics for thermal energy storage

In this paper, the structure‐property relationships of a clay ceramic with organic additives (biomass and biochar) are investigated to develop an alternative material for thermal energy storage. The firing transformations were elucidated using X‐ray pair distribution function analysis, differential scanning calorimetry, and scanning electron microscopy. It was found that the biomass increased the porosity, which resulted in a decrease of the specific heat capacity. On the other hand, the biochar remained in the clay ceramic without any interaction with the clay matrix up to 950°C. The specific heat capacity of the clay ceramic increased from 1.20 to 1.49 kJ/kg·K for a 30 wt% addition of biochar. The clay ceramic with a 30 wt% addition of biochar also conserved a high flexural strength of 11.1 MPa compared to that of the clay ceramic without organic additives (i.e., 18.9 MPa). Furthermore, the flexural strength only decreased by 23% after 100 thermal cycles. The crack growth associated with the thermal fatigue was limited by crack bridging and crack trapping. Hence, the current results suggest that clay/biochar ceramics can be as efficient as molten salts in thermal energy storage with the added benefit of an ease of use in the physical form of bricks.     

Identification of a Small‐Molecule Inhibitor of HIV‐1 Assembly that Targets the Phosphatidylinositol (4,5)‐bisphosphate Binding Site of the HIV‐1 Matrix Protein

The development of drug resistance remains a critical problem for current HIV‐1 antiviral therapies, creating a need for new inhibitors of HIV‐1 replication. We previously reported on a novel anti‐HIV‐1 compound, N²‐(phenoxyacetyl)‐N‐[4‐(1‐piperidinylcarbonyl)benzyl]glycinamide ( 14 ), that binds to the highly conserved phosphatidylinositol (4,5)‐bisphosphate (PI(4,5)P₂) binding pocket of the HIV‐1 matrix (MA) protein. In this study, we re‐evaluate the hits from the virtual screen used to identify compound 14 and test them directly in an HIV‐1 replication assay using primary human peripheral blood mononuclear cells. This study resulted in the identification of three new compounds with antiviral activity; 2‐(4‐{[3‐(4‐fluorophenyl)‐1,2,4‐oxadiazol‐5‐yl]methyl})‐1‐piperazinyl)‐N‐(4‐methylphenyl)acetamide ( 7 ), 3‐(2‐ethoxyphenyl)‐5‐[[4‐(4‐nitrophenyl)piperazin‐1‐yl]methyl]‐1,2,4‐oxadiazole ( 17 ), and N‐[4‐ethoxy‐3‐(1‐piperidinylsulfonyl)phenyl]‐2‐(imidazo[2,1‐b][1,3]thiazol‐6‐yl)acetamide ( 18 ), with compound 7 being the most potent of these hits. Mechanistic studies on 7 demonstrated that it directly interacts with and functions through HIV‐1 MA. In accordance with our drug target, compound 7 competes with PI(4,5)P₂ for MA binding and, as a result, diminishes the production of new virus. Mutation of residues within the PI(4,5)P₂ binding site of MA decreased the antiviral effect of compound 7 . Additionally, compound 7 displays a broadly neutralizing anti‐HIV activity, with IC₅₀ values of 7.5–15.6 μM for the group M isolates tested. Taken together, these results point towards a novel chemical probe that can be used to more closely study the biological role of MA and could, through further optimization, lead to a new class of anti‐HIV‐1 therapeutics.