First synthesis and in vitro biological assessment of isosideroxylin, 6, 8-dimethylgenistein and their analogues as nitric oxide production inhibition agents

A modular and efficient synthesis of the biologically significant C-methylisoflavones isosideroxylin(1),6,8-dimethylgenistein(2) and their analogues(3-8) is established for the first time.The synthesis is realized in 7-8 steps in overall yields of 16%-24%from commercially inexpensive phloroglucinol and features a high yielding Vilsmeier-Haack reaction,Friedel-Crafts acylation,Gammill's protocol and Suzuki coupling as the pivotal transformations.Next,these compounds evaluated for their inhibitory potency on the production of nitric oxide(NO) in lipopolysaccharide(LPS)-activated RAW-264.7 cells as an indicator of anti-inflammatory activity.The results showed that all the compounds decreased NO production in a dose-dependent manner without marked cytotoxicity and IC_(50) values are found in the range of 10.17-33.88 μmol/L.Of note,compounds 3 followed by 1,7 and 8 show comparable inhibitory activity with positive control(N-monomethyl-L-arginine,L-NMMA).     

Structural evolution and stabilities of neutral and anionic clusters of lead sulfide: joint anion photoelectron and computational studies

The geometric and electronic structures of both neutral and negatively charged lead sulfide clusters, (PbS)(n)/(PbS)(n)(-) (n = 2-10) were investigated in a combined anion photoelectron spectroscopy and computational study. Photoelectron spectra provided vertical detachment energies (VDEs) for the cluster anions and estimates of electron affinities (EA) for their neutral cluster counterparts, revealing a pattern of alternating EA and VDE values in which even n clusters exhibited lower EA and VDE values than odd n clusters up until n = 8. Computations found neutral lead sulfide clusters with even n to be thermodynamically more stable than their immediate (odd n) neighbors, with a consistent pattern also being found in their HOMO-LUMO gaps. Analysis of neutral cluster dissociation energies found the Pb(4)S(4) cube to be the preferred product of the queried fragmentation processes, consistent with our finding that the lead sulfide tetramer exhibits enhanced stability; it is a magic number species. Beyond n = 10, computational studies showed that neutral (PbS)(n) clusters in the size range, n = 11-15, prefer two-dimensional stacking of face-sharing lead sulfide cubical units, where lead and sulfur atoms possess a maximum of five-fold coordination. The preference for six-fold coordination, which is observed in the bulk, was not observed at these cluster sizes. Taken together, the results show a preference for the formation of slightly distorted, fused cuboids among small lead sulfide clusters.     

A mild and efficient stereoselective synthesis of (Z)- and (E)-allyl sulfides and potent antifungal agent, (Z)-3-(4-methoxybenzylidene)thiochroman-4-one from Morita-Baylis-Hillman acetates

A facile stereoselective synthesis of (Z)- and (E)-allyl sulfides has been accomplished from Morita-Baylis-Hillman acetates in one-pot by treatment with benzene thiol in the presence of catalytic amounts of 15% aqueous NaOH and TBAI in DMSO at room temperature. The method has been applied for the synthesis of (Z)-3-(4-methoxybenzylidene)thiochroman-4-one, a potent antifungal compound.     

Analysis of Damage and Failure in Anisotropic Ductile Metals Based on Biaxial Experiments with the H-Specimen

Background

Dependence of strength and failure behavior of anisotropic ductile metals on loading direction and on stress state has been indicated by many experiments. To realistically predict safety and lifetime of structures these effects must be taken into account in material models and numerical analysis.

Objective

The influence of stress state and loading direction on damage and failure behavior of the anisotropic aluminum alloy EN AW-2017A is investigated.

Methods

New biaxial experiments and numerical simulations have been performed with the H-specimen under different load ratios. Digital image correlation shows evolution of strain fields and scanning electron microscopy is used to visualize failure modes on fracture surfaces. Corresponding numerical studies predict stress states to explain damage and fracture processes on the micro-scale.

Results

The stress state, the load ratio and the loading direction with respect to the principal axes of anisotropy affect the width and orientation of localized strain fields and the formation of damage mechanisms and fracture modes at the micro-level.

Conclusions

The enhanced experimental program with biaxial tests considering different loading directions and load ratios is suggested for characterization of anisotropic metals.

     

The kinetics and mechanism of induced thermal decomposition of peroxomonosulphate by phase transfer catalysts

The kinetics of induced decomposition of potassium peroxomonosulphate (PMS) by the phase transfer catalysts (PTC), viz. tetrabutylammonium chloride [TBAC] and tetrabutylphosphonium chloride [TBPC] have been investigated. The effect of [PMS], [PTC], ionic strength of the medium and temperature on the rate of decomposition of PMS was studied. The rate of decomposition of PMS was monitored under pseudo-first-order condition at a constant temperature (50 ± 0.1 °C). The rate of decomposition was first order with respect to PMS for TBAC and half order for TBPC. The order with respect of PTC was found to be unity for TBAC and half order for TBPC. A suitable kinetic scheme has been proposed to account for the experimental data and its significance is discussed.     

Efficient,collective synthesis and nitric oxide inhibitory activity of rubrolides E,F, R,S and their derivatives

An efficient first synthesis of biologically significant natural butenolides, rubrolides F (1f), R (1r), S (1s) & its 7″,8″-didehydro derivative (1sa), and 3″-bromo rubrolide (1fa) along with the synthesis of rubrolide E (1e) and its di-O-methyl derivative (1ea) is accomplished in a collective fashion from commercially available and inexpensive precursors in overall yields of 14–48.5%. Key features are Wittig-Horner reaction, SeO₂-induced tandem allylic hydroxylation/intramolecular cyclization and Knoevenagel condensation. Next, in their inhibitory activity towards nitric oxide (NO) production in lipopolysaccharide-induced RAW 264.7 macrophages as an indicator of anti-inflammatory activity, all compounds displayed good inhibitory activity in a concentration-dependent manner. None of the compound exhibited notable cytotoxicity at the highest concentration (10 μM) and IC₅₀ values are found in the range from 8.53 to 17.85 μM.     

Infrared spectroscopic confirmation of α‐lactone formation in the dissociation of a gaseous amino acid

The product obtained upon collision‐induced dissociation of sulfonated phenylalanine in the gas phase has been investigated by using infrared multiphoton dissociation spectroscopy with a free‐electron laser. This confirms that the product formed by loss of ammonia from the amino acid is the α‐lactone, as had been deduced previously based on qualitative analysis and electronic structure calculations. Spectroscopically, the structure is confirmed by the presence of the carbonyl stretching peak at 1915 cm^?1 and supported by excellent agreement between the predicted and observed S–O stretching bands. The agreement between predicted relative intensities is not as good, but can be attributed to the nonlinear process of IRMPD. Copyright © 2016 John Wiley & Sons, Ltd.     

Photoconductivity and hole transport in polymers of aromatic amine-containing methacrylates

Substantial hole transport can be achieved in organic polymers simply by incorporating aromatic amine groups into the monomer. Hole mobilities similar to or greater than those in poly(N-vinyl-carbazole) (PVK) were measured in a series of high molecular weight arylamine-substituted polymethacrylates. The hole transport in these polymers is electric-field-dependent as in PVK, varying between E and E² within a range of 4 × 10⁴ ? ～9 × 10⁵ V/cm. The polymers also exhibit carrier generation in ultraviolet (UV) light in the range of absorption. Synthesis of the monomers, their polymerization, and the general properties of these polymers are discussed.     

Click Chemistry Assisted Single-Molecule Fingerprinting Reveals a 3D Biomolecular Folding Funnel

A 3D folding funnel was proposed in the 1990s to explain the fast kinetics exhibited by a biomacromolecule in presence of seemingly unlimited folding pathways. Over the years, numerous simulations have been performed with this concept; however, experimental verification is yet to be attained even for the simplest proteins. Here, we have used a click chemistry based strategy to introduce six pairs of handles in a human telomeric DNA sequence. A laser-tweezers-based, single-molecule structural fingerprinting on the six inter-handle distances reveals the formation of a hybrid-1 G-quadruplex in the sequence. Kinetic and thermodynamic fingerprinting on the six trajectories defined by each handle-pair depict a 3D folding funnel and a kinetic topology in which the kinetics pertaining to each handle residue is annotated for this G-quadruplex. We anticipate the methods and the concepts developed here are well applicable to other biomacromolecules, including RNA and proteins.