Ureidosulfocoumarin Derivatives As Selective and Potent Carbonic Anhydrase IX and XII Inhibitors

Owing to severe allergic reactions (anaphylaxis) and resistance exhibited by sulfonamide-based carbonic anhydrase (CA) inhibitors, non-classical or non-sulfonamide CA inhibitors are gaining increased attention by medicinal chemists. In this context, we report the design and synthesis of 30 new non-sulfonamide sulfocoumarin derivatives as CA inhibitors. They were investigated against hCA I and II (cytosolic isozymes) as well as hCA IX and XII (transmembrane, tumor-associated enzymes). All compounds showed prominent selectivity for the tumor-associated isoenzymes hCA IX and XII over the cytosolic isoenzymes hCA I and II. Among all synthesized compounds, 1-(2,2-dioxidobenzo[e][1,2]oxathiin-6-yl)-3-(o-tolyl)urea( 5 j )and1-(3-fluorophenyl)-3-(8-methoxy-2,2-dioxidobenzo[e][1,2]oxathiin-6-yl)urea( 5 q )were found to be more potent and to have better inhibition constant values against hCA IX than the standard acetazolamide (AAZ), with K_i values of 23.6 and 23.3 nM, respectively. All other compounds were found to be active under K_i=920 nM against hCA IX and XII.This study provides a new perspective for the future development of non-sulfonamide derivatives as selective CA inhibitors.     

Molecular interaction and properties of poly(ether ether ketone)/liquid crystalline polymer blends incorporated with functionalized carbon nanotubes

Multi-walled carbon nanotubes (MWCNTs) were functionalized with a carboxyl group (-COOH) to achieve better interfacial adhesions with both phases of the poly(ether ether ketone) (PEEK) and liquid crystalline polymer (LCP) in their blend. These strong interfacial interactions among the functionalized MWCNTs, PEEK and LCP improved the mechanical properties of the polymer blend. Three different weight percentages (0.6%, 1.2% and 1.8%) of acid modified CNTs were used with PEEK-LCP blend, for the preparation of nanocomposites. In PEEK-LCP blend, the ratio of PEEK and LCP was maintained as 10:6 respectively. The tensile strength and modulus of the composites were improved by 51% and 73% respectively with the incorporation of only 1.2% of MWCNT-COOH as compared to the unfilled PEEK/LCP blend. Moreover, careful studies of the molecular interaction, morphological, dynamic mechanical and thermal properties confirmed that a better miscibility between PEEK and LCP had been constituted in the presence of MWCNT-COOH. Therefore, it was found that the functionalized MWCNTs not only played the traditional role as reinforcing filler, but also performed a novel role as a compatibilizer for the PEEK/LCP blends.     

Failure Analysis of Radiant Tube Burners in Continuous Annealing Line (CAL) of an Integrated Steel Plant

Failure analysis of radiant tube burners (ACI HK 40 with composition ~25 wt.% Cr, ~20 wt.% Ni) removed from a continuous annealing line (CAL) of a cold rolling mill (CRM) of an integrated steel plant was performed using optical microscopy (OM), scanning electron microscopy (SEM), electron probe microanalysis (EPMA), and microhardness measurements. Studies revealed that the failures were mainly attributed to combined influences of creep and carburization-assisted localized oxidative attack. A suitable heat-resisting cast austenitic stainless steel was identified as a candidate alloy to replace the previously used ACI HK 40 alloy.     

Improvement of grinding characteristics of Indian coal by microwave pre-treatment

The influence of microwave pretreatment on the grindability of high-ash Indian coal was investigated. Scanning electron microscope analysis characterized the micro fractures in microwave treated coal samples, which may be due to the thermal stress cracking resulting from the microwave pretreatment. X-ray diffraction analysis showed that the microwave treated coal had a higher peak compared to the untreated coal indicates that the crystallinity increased with the microwave exposure time. The calculation of the Hardgrove grindability index indicated an increase in the ease of grinding or an increase in the grindability index of the microwave treated coal. Bond grindability tests showed that the work index decreased 15.4% after a microwave exposure time of 120 s. Grindability tests showed that the microwave treated coal ground much more rapidly initially than the untreated coal, with the specific rate of breakage (S₁) increasing by an average of 15%. The results showed that the rates of breakage of both microwave untreated and treated coal samples were dependent on particle size.     

Synthesis, characterization and densification of WCu nanocomposite powders

In the present investigation, W20-40wt.% Cu nanocomposite powders with average sizes ranging between 25 and 30 nm were synthesized by a soft chemical approach using tungsten hexacarbonyl [W(CO)₆] and copper acetonyl acetonate [Cu(acac)₂] as metal precursors. Particle size, morphology and distribution were measured using transmission electron microscope (TEM) and small angle X-ray scattering (SAXS). Surfactant coating on WCu composite powders was removed on heat treatment of powders at 450 °C in hydrogen atmosphere for 1 h. Elemental analyses of as-synthesized and annealed (at 450 °C) WCu nanocomposite powders were carried out using inductively coupled plasma-optical emission spectrometer (ICP-OES) and Leco gas analyzers. X-ray diffraction studies showed that the tungsten phase is amorphous while the crystal structure of copper phase is fcc in as-synthesized WCu nanocomposite powders. After annealing at 700 °C peaks corresponding to bcc tungsten are observed and peaks corresponding to fcc copper become sharper. Relative densities of 98.2%, 98.8% and 99.2% were achieved for W20wt.% Cu, W30wt.% Cu, and W40wt.% Cu composite powders respectively when sintered at 1000 °C.     

Dissolution enhancement of a poorly water-soluble antimalarial drug by means of a modified multi-fluid nozzle pilot spray drier

A spray drier with a modified multi-fluid nozzle was used to prepare microparticles of a poorly water-soluble antimalarial drug, artemisinin (ART), with the aim of improving its dissolution in water. ART was co-spray dried with a hydrophilic polymer, polyethylene glycol (PEG). The differential scanning calorimetry and X-ray diffraction studies showed that the crystallinity of ART decreased after spray drying. Compared to the physical mixture of ART and PEG, the amorphous phase of ART in the spray dried ART–PEG composites increased, which depended on the weight ratio of drug to polymer. The phase-solubility studies revealed that the aqueous solubility of ART was improved by the presence of PEG. The dissolution of ART from the spray dried ART–PEG composites was more rapid than that from their respective physical mixture and the original ART powder. For example, the dissolution of ART from the spray dried ART–PEG composite (1:6) was 6.5 times higher than that from the original ART powder in the first 30 min. In the mathematical modeling, the Weibull and Korsemeyer–Peppas models were found to best fit to the in vitro dissolution data and then the drug release mechanism was considered as the Fickian diffusion.     

Synthesis and characterization of porous ZnO nanoparticles by hydrothermal treatment of as pure aqueous precursor

The presence of the complexing agents in the growth solution poses risk of the unintentional doping in the synthesized product and hence is likely to adversely affect the intrinsic properties. Herein we report the synthesis of ZnO nanoparticles with porous microstructure using pure aqueous precursor. Crystalline ZnO nanoparticles were synthesized by thermal treatment of aqueous solution of zinc acetate in an open bath. The size of the nanocrystals was controlled by changing the initial precursor concentration. The structural and optical properties of the synthesized nanocrystals were analyzed by X-ray diffraction, high resolution transmission electron microscopy, UV-vis absorption and room temperature photoluminescence measurement techniques. The TEM and UV-vis spectral signature analyses confirmed the formation of dispersed single crystalline ZnO nanoparticles. The nanopowders were found to have disordered mesoporous structure. The synthesized nanocrystals exhibited characteristic band edge emission as well as to surface defect related deep level visible luminescence.     

Thermal characteristics of forced convection in combined pressure and shear-driven flow of a non-Newtonian third-grade fluid through parallel plates

Heat transfer in a non-Newtonian third-grade fluid, flowing under the action of pressure gradient and shear, through two parallel plates, is considered. The upper plate moves with a constant velocity. Constant wall heat fluxes are applied to the plates. Effect of viscous dissipation is included, which has a major role in heat transfer of non-Newtonian fluids. The governing equations are nonlinear and are solved semi-analytically by using the least-square method (LSM). Then, using the solution for velocity in the energy equation, the solution is obtained by a direct integration process. Further, approximate analytical solutions are obtained by the perturbation method, which validates the results generated by the LSM. The effects of the third-grade fluid parameter on the velocity and temperature and also on the physical quantity, such as Nusselt's number, are discussed. Further, viscous dissipation effects on the temperature distribution have been analyzed. Observations show that the movement of the upper plate results in a significant decrease in temperature near the upper plate. For the unit heat flux ratio, the temperature difference between the surface and fluid is more at the upper surface due to the enhanced convective heat transfer caused by the moving upper plate. Nusselt's number increases significantly with an increase in the heat flux ratio.     

3‐Substituted Indazoles as Configurationally Locked 4EGI‐1 Mimetics and Inhibitors of the eIF4E/eIF4G Interaction

4EGI‐1, the prototypic inhibitor of eIF4E/eIF4G interaction, was identified in a high‐throughput screening of small‐molecule libraries with the aid of a fluorescence polarization assay that measures inhibition of binding of an eIF4G‐derived peptide to recombinant eIF4E. As such, the molecular probe 4EGI‐1 has potential for the study of molecular mechanisms involved in human disorders characterized by loss of physiological restraints on translation initiation. A hit‐to‐lead optimization campaign was carried out to overcome the configurational instability in 4EGI‐1, which stems from the E‐to‐Z isomerization of the hydrazone function. We identified compound 1 a , in which the labile hydrazone was incorporated into a rigid indazole scaffold, as a promising rigidified 4EGI‐1 mimetic lead. In a structure–activity relationship study directed towards probing the structural latitude of this new chemotype as an inhibitor of eIF4E/eIF4G interaction and translation initiation we identified 1 d , an indazole‐based 4EGI‐1 mimetic, as a new and improved lead inhibitor of eIF4E/eIF4G interaction and a promising molecular probe candidate for elucidation of the role of cap‐dependent translation initiation in a host of pathophysiological states.     

Dielectric relaxation behavior of conducting carbon black reinforced ethylene acrylic elastomer vulcanizates

The dielectric relaxation characteristics of conductive carbon black (CCB) reinforced ethylene acrylic elastomer (AEM) vulcanizates have been studied as a function of frequency (10¹–10⁶ Hz) at different filler loading over a wide range of temperatures (30–120°C). The effect of filler loadings on the dielectric permittivity (ε′), loss tangent (tan δ), complex impedance (Z*), and electrical conductivity (σ_ac) were studied. The variation of ε′ with filler loading has been explained based on the interfacial polarization of the fillers within a heterogeneous system. The effect of filler loading on the imaginary (Z″) and real (Z′) part of Z* were distinctly visible, which may be due to the relaxation dynamics of polymer chains at the polymer–filler interface. The frequency dependency of σ_ac has been investigated using percolation theory. The phenomenon of percolation in the composites has been discussed in terms of σ_ac. The percolation threshold (?_crit) occurred in the range of 20–30 phr (parts per hundred) of filler loading. The effect of temperature on tan δ, ε′, σ_ac, and Nyquist plots of CCB‐based AEM vulcanizates has been investigated. The CCB was uniformly dispersed within the AEM matrix as studied from the transmission electron microscope (TEM) photomicrographs. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012