Study of phase transformation and elastic properties of ThX (X = N,P, As and Sb) under high-pressure

An improved interaction potential model (IIPM) has been formulated to theoretically predict the pressure induced phase transition, elastic properties and thermophysical properties of thorium monopnictides (ThX; X = N, P, As and Sb). The phase transition pressures and volume drop obtained from this model show a better agreement with the available experimental than theoretical results. We have achieved elastic moduli, anisotropy factor, Poisson's ratio, Kleinman parameter, shear and stiffness constants on the basis of the calculated elastic constants. To know the anharmonic properties, we have also computed the third-order elastic constants, first-order pressure derivatives of second-order elastic constants and thermophysical quantities. Our results are in reasonable agreement with available measured and others reported data which supports the validity of model.     

Synthesis of Polycyclic Ether-Benzopyrans and In Vitro Inhibitory Activity against Leishmania tarentolae

Construction of a focused library of polycyclic ether-benzopyrans was undertaken in order to discover new therapeutic compounds that affect Leishmania growth and infectivity. This is especially of interest since there are few drug therapies for leishmaniasis that do not have serious drawbacks such high cost, side effects, and emerging drug resistance. The construction of these polycyclic ether-benzopyrans utilized an acetoxypyranone-alkene [5+2] cycloaddition and the Suzuki-Miyaura cross-coupling. The multi-gram quantity of the requisite aryl bromide was obtained followed by effective Pd-catalyzed coupling with boronic acid derivatives. Compounds were tested in vitro using the parasitic protozoan, Leishmania tarentolae. Effects of concentration, time, and exposure to light were evaluated. In addition, the effects on secreted acid phosphatase activity and nitric oxide production were investigated, since both have been implicated in parasite infectivity. The data presented herein are indicative of disruption of the Leishmania tarentolae and thus provide impetus for the development and testing of a more extensive library.     

Identification of nitroglycerin‐induced cysteine modifications of pro‐matrix metalloproteinase‐9

Nitroglycerin (NTG), an important cardiovascular agent, has been shown recently to activate matrix metalloproteinase‐9 (MMP‐9) in biological systems, possibly leading to destabilization of atherosclerotic plaques. The chemical mechanism for this activation, particularly on the cysteine switch of the pro‐form of MMP‐9 (proMMP‐9), has not been investigated and was examined here using nano‐flow liquid chromatography coupled to mass spectrometry. In order to obtain high sequence coverage, two orthogonal enzymes (trypsin and GluC) were employed to digest the protein in parallel. Two complementary activation methods, collision‐induced dissociation (CID) and electron‐transfer dissociation (ETD), were employed for the identification of various modifications. A high‐resolution Orbitrap analyzer was used to enable confident identification. Incubation of NTG with proMMP‐9 resulted in the formation of an unstable thionitrate intermediate and oxidation of the cysteine switch to sulfinic and irreversible sulfonic acid derivatives. The unstable thionitrate modification was confirmed by both CID and ETD in the proteolytic peptides produced by both trypsin and GluC. Incubation of proMMP‐9 with diethylenetriamine NONOate (a nitric oxide donor) led to sulfonic acid formation, but no observable sulfinic acid modification. Extensive tyrosine nitration by NTG was observed at Tyr‐262, in close proximity to an oxidized Cys‐256 of proMMP‐9. The intramolecular interaction between these two residues toward NTG‐induced oxidation was examined using a synthesized peptide representing the sequence in this domain, PWCSTTANYDTDDR, and the modification status was compared against an analog in which Cys was substituted by Ala. We observed a thionitrate product, extensive Cys oxidative modifications and enhanced tyrosine nitration with the Cys peptide but not with the Ala analog. Our results indicated that neighboring Cys and Tyr residues can facilitate each other's oxidation in the presence of NTG. Copyright © 2011 John Wiley & Sons, Ltd.     

Intensity noise reduction in a multiwavelength distributed Bragg reflector fiber laser

Noise reduction in a multiwavelength distributed Bragg reflector fiber laser was demonstrated. A 20 dB reduction of in-phase intensity noise was achieved by using negative feedback to modulate the drive current of the laser pump diode. Strategies for reducing antiphase noise components are discussed.     

Facile SILAR Processed Bi2S3:PbS Solid Solution on MWCNTs for High‐performance Electrochemical Supercapacitor

Carbon based composite materials have gained much attention because of fulfilling desirable properties for supercapacitor application. In the featured work, the thin film of Bi₂S₃:PbS solid solution has been synthesized on multi‐walled carbon nanotubes (MWCNTs) by simple successive ionic layer adsorption and reaction (SILAR) method. The nanoparticle morphology provides sufficient electroactive channels for electrolyte ions to penetrate during electrochemical activities. The composite exhibits superior specific capacitance 676 F/g at constant specific current density of 5.56 A/g with fast charge‐discharge cycles. In association of energy storage characteristics, the fabricated symmetric cell exhibits excellent energy density of 13.36 Wh/kg by acquiring power density of 0.83 kW/kg. The superior results of the hybrid electrode promise a novel direction for high performance supercapacitor application.     

Synthesis,Docking, and Pharmacological Evaluation of Derivatives of α‐Aminoketones Appended to Sydnones as Potent Antitubercular and Antifungal Scaffolds

3‐Arylsydnones are reported to possess striking pharmaceutical potency. α‐Aminoketone, a biologically active structural unit, is built at the fourth (electrophilic) position of sydnone and further derivatized with secondary amine and tetrazoles. The α‐aminoketone derivatives of sydnones coupled with secondary amines 4a – n were docked on enoyl acyl carrier protein (ACP) reductase from Mycobacterium tuberculosis, which revealed that compounds 4b , 4f , and 4i showed efficient C score values with different binding modes and hydrogen bonding. Further, these compounds were screened for antimycobacterial activity; among them, compound 4f displayed sensitivity at 6.25 μg/mL compared with the standard drug (Streptomycin) against M. tuberculosis (H₃₇R_V strain). In addition to this, α‐aminoketone derivatives of sydnones coupled with tetrazoles 8a – h were evaluated for antifungal activity. In the antifungal activity, compound 8b has exhibited potent activity at 6.25 μg/mL against Candida albicans and compound 8g at 0.4 μg/mL against Aspergillus fumigatus. The antifungal activities are comparatively better than standard antifungal agent Fluconazole at these drug concentrations. Alongside characterization of the final compounds by Fourier transform infrared, mass, ¹H NMR, and ¹³C NMR spectral analyses, compounds 8b and 8g were confirmed by X‐ray crystallographic studies.     

Gene Interaction Network Analysis Reveals IFI44L as a Drug Target in Rheumatoid Arthritis and Periodontitis

Simple SummaryIn spite of substantial investigation, the biological link between periodontitis and rheumatoid arthritis remains unexplained. This study intended to correlate periodontitis and rheumatoid arthritis gene expression patterns to find shared targets for both the disease. We identified the differentially expressed genes (DEGs) in periodontitis and rheumatoid arthritis. The network was built by integrating DEGs and ranking the genes using GeneMANIA. FINDSITEcomb2.0 was used to find a possible inhibitor for the top-ranked gene. Further, the binding effectiveness and protein-ligand complex stability were then determined by molecular docking and molecular dynamics. The network analysis showed IFI44L as a highly ranking gene implicated in most immunological pathways. A virtual screening of 6507 compounds revealed vemurafenib as the best candidate for the IFI44L target. Molecular docking and molecular dynamics modelling revealed the stability of the IFI44L-vemurafenib complex, which suggest IFI44L is potential target and vemurafenib could be the better candidate to treat both diseases.AbstractObjective: Despite extensive research on periodontitis and rheumatoid arthritis, the underlying molecular connectivity between these condition remains largely unknown. This research aimed to integrate periodontitis and rheumatoid arthritis gene expression profiles to identify interconnecting genes and focus to develop a common lead molecule against these inflammatory conditions. Materials and Methods: Differentially expressed genes (DEGs) of periodontitis and rheumatoid arthritis were identified from the datasets retrieved from the Gene Expression Omnibus database. The network was constructed by merging DEGs, and the interconnecting genes were identified and ranked using GeneMANIA. For the selected top ranked gene, the potential inhibitor was searched using FINDSITE^comb2.0. Subsequently, the molecular docking and molecular dynamics were performed to determine the binding efficiency and protein-ligand complex stability, respectively. Results: From the network analysis, IFN-induced protein 44-like (IFI44L) was identified as a top ranked gene involved in most of the immunological pathway. With further virtual screening of 6507 molecules, vemurafenib was identified to be the best fit against the IFI44L target. The binding energy and stability of IFI44L with vemurafenib were investigated using molecular docking and molecular dynamics simulation. Docking results show binding energy of −7.7 Kcal/mol, and the simulation results show stability till 100 ns. Conclusions: The identified IFI44L may represent a common drug target for periodontitis and rheumatoid arthritis. Vemurafenib could be a potent anti-inflammatory drug for both diseases.     

A novel eco-friendly on-water protocol for the synthesis of 2,2-disubstituted 2,3-dihydro-1H-perimidines

An efficient green on-water protocol for the synthesis of 2,2-disubstituted 2,3-dihydro-1H-perimidines is demonstrated. The reaction used safer p-toluenesulfonic acid (PTSA) as a catalyst on water at 80°C, for 2 hours affording a novel method for the synthesis of various disubstituted perimidines in moderate to excellent yields.     

Visible-light mediated regioselective approach towards synthesis of 7-aroyl-6-methyl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines

The first visible-light mediated, simple, efficient and ecofriendly protocol for the regioselective synthesis of novel [1,2,4]triazolo[3,4-b][1,3,4]thiadiazines has been developed by the reaction of α-bromodiketones, generated in situ by the bromination of a diverse array of β-diketones with N-bromosuccinimide, with 4-amino-[1,2,4]triazole-3-thiols. The methodology does not require the presence of any additives and this reaction proceeded in the presence of EDG (OMe), EWG (Cl) and heteroarenes (thiophenyl) giving the expected products in good to excellent yields. A solvent free protocol was also established to accomplish the synthesis of target compounds but it required PTSA as a catalyst and yields are comparatively poor. The structure of the regioisomer has been confirmed unambiguously by heteronuclear 2D-NMR [(¹H-¹³C) HMBC, (¹H-¹⁵N) HMBC, (¹H-¹³C) HMQC] spectroscopic and X-ray crystallographic studies.