New parasite inhibitors encompassing novel conformationally-locked 5'-acyl sulfamoyl adenosines

We describe the design, synthesis and biological evaluation of conformationally-locked 5'-acyl sulfamoyl adenosine derivatives as new parasitic inhibitors against Trypanosoma and Leishmania. The conformationally-locked (3'-endo, North-type) nucleosides have been synthesized by covalently attaching a 4'-CH(2)-O-2' bridge () across C2'-C4' of adenosine in order to reduce the conformational flexibility of the pentose ring. This is designed to decrease the entropic penalty for complex formation with the target protein, which may improve free-energy of stabilization of the complex leading to improved potency. Conformationally-locked 5'-acyl sulfamoyl adenosine derivatives (16-22) were tested against parasitic protozoans for the first time in this work, and showed potent inhibition of Trypanosoma cruzi, Trypanosoma brucei, Trypanosoma rhodesiense and Leishmania infantum with IC(50) = 0.25-0.51 μM. In particular, the potent 5'-pentanyl acyl sulfamoyl adenosine derivative 17 (IC(50) = 0.25 μM) against intracellular L. infantum amastigotes and Trypanosoma subspecies is interesting in view of its almost insignificant cytotoxicity in murine macrophage host cells (CC(50) >4 μM) and in diploid human fibroblasts MRC-5 cell lines (CC(50) 4 μM). This work also suggests that variable alkyl chain length of the acyl group on the acylsulfamoyl side chain at 5' can modulate the toxicity of 5'-O-sulfamoylnucleoside analogues. This conformationally-locked sulfamoyl adenosine scaffold presents some interesting possibilities for further drug design and lead optimization.     

Design and synthesis of fluorescent 6-aryl[1,2-c]quinazolines serving as selective and sensitive ‘on-off’ chemosensor for Hg in aqueous media

Three fluorescent quinazolines thiophen-2-yl-5,6-dihydrobenzo-[4,5]imidazo[1,2-c]quinazoline (1), pyridin-3-yl-5,6-dihydrobenzo-[4,5]imidazo-[1,2-c]quinazoline (2) and phenyl-5,5′,6,6′-dihydrobenzo-[4,4′,5,5′]imidazo-[1.1′,2-c,2′-c]quinazoline (3) have been synthesized. Structures of 1 and 3 have been authenticated crystallographically. Quinazolines 1-3 exhibit highly selective ‘on-off’ switching for Hg²⁺ ions. The fluorescence intensity displayed a linear relationship with respect to Hg²⁺ concentration (0.1-1.0 μM; R² = 0.99) with detection limit of 2.0 × 10⁻⁷ M.     

Time dependent stretching of aging dynamics in a generalized hydrodynamic model for supercooled liquids

The nonequilibrium dynamics and aging behavior of a supercooled liquid is investigated from an analysis of the correlation of density fluctuations at two different times. The dynamic correlation functions are computed by solving numerically the equations of nonlinear fluctuating hydrodynamics. The aging time dependence follows a modified stretched exponential form with a relaxation time which is dependent on the aging time. This is similar to the behavior seen in the aging data of dielectric response functions of a typical glass forming liquid.     

In-plane fracture of laminated fiber reinforced composites with varying fracture resistance: Experimental observations and numerical crack propagation simulations

A series of experimental results on the in-plane fracture of a fiber reinforced laminated composite panel is analyzed using the variational multiscale cohesive method (VMCM). The VMCM results demonstrate the influence of specimen geometry and load distribution on the propagation of large scale bridging cracks in the fiber reinforced panel. Experimentally observed variation in fracture resistance is substantiated numerically by comparing the experimental and VMCM load–displacement responses of geometrically scaled single edge-notch three point bend (SETB) specimens. The results elucidate the size dependence of the traction-separation relationship for this class of materials even in moderately large specimens, contrary to the conventional understanding of it being a material property. The existence of a “free bridging zone” (different from the conventional “full bridging zone”) is recognized, and its influence on the evolving fracture resistance is discussed. The numerical simulations and ensuing bridging zone evolution analysis demonstrates the versatility of VMCM in objectively simulating progressive crack propagation, compared against conventional numerical schemes like traditional cohesive zone modeling, which require a priori knowledge of the crack path.     

Strategies for the synthesis of fluorescently labelled PNA

A simple and effective strategy for preparing fluorophore-labelled PNA is described. A C-terminal S-t-butylmercaptocysteine-derivatized PNA was prepared on solid-phase using Fmoc chemistry. Selective deprotection of the S-t-butylmercapto group on-bead, allowed the free thiol to be reacted with a fluorophore derivatized via an iodoacetamido or maleimido linker. Subsequent cleavage and sidechain deprotection yielded C-terminal labelled PNA in good yield and purity. Dual labelled PNA was also prepared by using both C-terminal (-SH) and N-terminal (-NH(2)) labelling chemistries.     

Purification and Characterization of Gum-Derived Polysaccharides of Moringa oleifera and Azadirachta indica and Their Applications as Plant Stimulants and Bio-Pesticidal Agents

Plant gums are bio-organic substances that are derived from the barks of trees. They are biodegradable and non-adverse complex polysaccharides that have been gaining usage in recent years due to a number of advantages they contribute to various applications. In this study, gum was collected from Moringa oleifera and Azadirachta indica trees, then dried and powdered. Characterizations of gum polysaccharides were performed using TLC, GC-MS, NMR, etc., and sugar molecules such as glucose and xylose were found to be present. Effects of the gums on Abelmoschus esculentus growth were observed through root growth, shoot growth, and biomass content. The exposure of the seeds to the plant gums led to bio stimulation in the growth of the plants. Poor quality soil was exposed to the gum polysaccharide, where the polysaccharide was found to improve soil quality, which was observed through soil analysis and SEM analysis of soil porosity and structure. Furthermore, the plant gums were also found to have bio-pesticidal activity against mealybugs, which showed certain interstitial damage evident through histopathological analysis.     

High‐mobility solution‐processed zinc oxide thin films on silicon nitride

A high effective electron mobility of 33 cm² V^–1 s^–1 was achieved in solution‐processed undoped zinc oxide (ZnO) thin films. The introduction of silicon nitride (Si₃N₄) as growth substrate resulted in a mobility improvement by a factor of 2.5 with respect to the commonly used silicon oxide (SiO₂). The solution‐processed ZnO thin films grown on Si₃N₄, prepared by low‐pressure chemical vapor deposition, revealed bigger grain sizes, lower strain and better crystalline quality in comparison to the films grown on thermal SiO₂. These results show that the nucleation and growth mechanisms of solution‐processed films are substrate dependent and affect the final film structure accordingly. The substantial difference in electron mobilities suggests that, in addition to the grain morphology and crystalline structure effects, defect chemistry is a contributing factor that also depends on the particular substrate. In this respect, interface trap densities measured in high‐κ HfO₂/ZnO MOSCAPs were about ten times lower in those fabricated on Si₃N₄ substrates. (© 2014 WILEY‐VCH Verlag GmbH &Co. KGaA, Weinheim)

     

Assessment of sandwich models for the prediction of sound transmission loss in unidirectional sandwich panels

The consistent higher-order approach and the two-parameter foundation formulation are used for the derivation of sound transmission loss in symmetric unidirectional (infinitely wide) sandwich panels with isotropic face sheets. In both models, transmission loss is calculated using decoupled equations representing symmetric and anti-symmetric motions of a sandwich panel. The closed-form expressions for impedances and transmission coefficient of a symmetric sandwich panel with an isotropic core are derived for the two-parameter foundation model. A comparison between the numerical predictions based on the two sandwich models and available experimental data shows that the consistent higher-order formulation can be used to predict the transmission loss in symmetric sandwich panels with both honeycomb and isotropic cores. For prediction of transmission loss of symmetric sandwich panels with an isotropic core, the two-parameter foundation model is more convenient, while the consistent higher-order approach is more accurate.