Reactions of enaminones and related compounds with N,N-dimethylacetamide dimethyl acetal. A simple one-pot metal-free synthesis of polysubstituted benzene derivatives

Herein a simple one-pot metal-free synthesis of alkyl-, aryl-, heteroaryl- and alkoxycarbonyl substituted 1,3-bis(dimethylamino)benzene derivatives is described. The products were prepared from the corresponding methyl ketones or compounds with an α-methylene group in regard to the carbonyl group, using N,N-dimethylacetamide dimethyl acetal (DMADMA) as the reagent.     

A novel approach to measure isotope ratios via multi-collector—inductively coupled plasma—mass spectrometry based on sample mixing with a non-enriched standard

In this work, a novel approach to measure isotope ratios via multi-collector—inductively coupled plasma—mass spectrometry (MC-ICP-MS) for low amounts of target element is proposed. The methodology is based on mixing of the sample (target element isolate) with a non-enriched in-house standard, previously characterized for its isotopic composition. This methodology has been applied to isotopic analysis of Cu and of Fe in whole blood samples. For this purpose, different mixtures of sample + in-house standard were prepared and adjusted to a final concentration of 500 μg/L of the target elements for isotopic analysis. δ⁶⁵Cu, δ⁵⁶Fe, and δ⁵⁷Fe varied linearly as a function of the amount of in-house standard (or of sample) present in the mixture. The isotopic composition of the sample was calculated considering the isotope ratios measured for (i) the mixture and (ii) the in-house standard and (iii) the relative concentrations of target element contributed by the sample and the standard to the mixture, respectively. For validation purposes, the isotopic analysis of whole blood Cu was carried out using both the conventional (using 2 mL of whole blood) and the newly developed approach (using 500 μL of whole blood). The δ⁶⁵Cu values obtained using mixtures containing 40 % (200 μg/L) of Cu from the blood samples and 60 % (300 μg/L) of Cu from the in-house standard were in good agreement with the δ⁶⁵Cu value obtained using the conventional approach (bias ≤0.15?‰).     

A validated stability-indicating LC method for simultaneous determination of quinapril and hydrochlorothiazide in pharmaceutical samples

A stability-indicating liquid chromatographic method was developed and validated for simultaneous determination of quinapril and hydrochlorothiazide in drug substances and dosage forms. Chromatographic separation of quinapril, hydrochlorothiazide and its degradation products was achieved on a RP-18 column, using acetonitrile and phosphate buffer (pH 4.6) as mobile phase in a gradient mode and detection at 216 nm. Stress testing was performed under hydrolytic, oxidative, thermal and photolytic conditions. The degradation products were well resolved from main peaks, proving the stability-indicating power of the method. The assay was linear for quinapril and hydrochlorothiazide concentrations of 40–200 µg mL^?1 and 25–125 µg mL^?1, respectively. The developed method was selective, accurate and precise for quinapril and hydrochlorothiazide determination. This method was used to quantify both drugs in combined commercial tablets. The results showed that the proposed method was found to be suitable for quantitative determination and the stability study of quinapril and hydrochlorothiazide in pharmaceutical samples.      

Tacrines as Therapeutic Agents for Alzheimer's Disease. V. Recent Developments

Herein we have reviewed our recent developments for the identification of new tacrine analogues for Alzheimer's disease (AD) therapy. Tacrine, the first cholinesterase inhibitor approved for AD treatment, did not stop the progression of AD, producing only some cognitive improvements, but exhibited secondary effects mainly due to its hepatotoxicity. Thus, the drug was withdrawn from the clinics administration. Since then, many publications have described non‐hepatotoxic tacrines, and in addition, important efforts have been made to design multitarget tacrines by combining their cholinesterase inhibition profile with the modulation of other biological targets involved in AD.     

Two Ecdysteroids Isolated from Micropropagated Lychnis flos-cuculi and the Biological Activity of Plant Material

Genetically uniform plant material, derived from Lychnis flos-cuculi propagated in vitro, was used for the isolation of 20-hydroxyecdysone and polypodine B and subjected to an evaluation of the antifungal and antiamoebic activity. The activity of 80% aqueous methanolic extracts, their fractions, and isolated ecdysteroids were studied against pathogenic Acanthamoeba castellani. Additionally, a Microtox^® acute toxicity assay was performed. It was found that an 80% methanolic fraction of root extract exerts the most potent amoebicidal activity at IC₅₀ of 0.06 mg/mL at the 3rd day of treatment. Both ecdysteroids show comparable activity at IC₅₀ of 0.07 mg/mL. The acute toxicity of 80% fractions at similar concentrations is significantly higher than that of 40% fractions. Crude extracts exhibited moderate antifungal activity, with a minimum inhibitory concentration (MIC) within the range of 1.25–2.5 mg/mL. To the best of our knowledge, the present report is the first to show the biological activity of L. flos-cuculi in terms of the antifungal and antiamoebic activities and acute toxicity. It is also the first isolation of the main ecdysteroids from L. flos-cuculi micropropagated, ecdysteroid-rich plant material.     

Mono‐ and Bis(pyrrolo)tetrathiafulvalene Derivatives Tethered to C60: Synthesis,Photophysical Studies,and Self‐Assembled Monolayers

A series of mono‐ (MPTTF) and bis(pyrrolo)tetrathiafulvalene (BPTTF) derivatives tethered to one or two C₆₀ moieties was synthesized and characterized. The synthetic strategy for these dumbbell‐shaped compounds was based on a 1,3‐dipolar cycloaddition reaction between aldehyde‐functionalized MPTTF/BPTTF derivatives, two different tailor‐made amino acids, and C₆₀. Electronic communication between the MPTTF/BPTTF units and the C₆₀ moieties was studied by a variety of techniques including cyclic voltammetry and absorption spectroscopy. These solution‐based studies indicated no observable electronic communication between the MPTTF/BPTTF units and the C₆₀ moieties. In addition, femtosecond and nanosecond transient absorption spectroscopy revealed, rather surprisingly, that no charge transfer from the MPTTF/BPTTF units to the C₆₀ moieties takes place on excitation of the fullerene moiety. Finally, it was shown that the MPTTF–C₆₀ and C₆₀–BPTTF‐C₆₀ dyad and triad molecules formed self‐assembled monolayers on a Au(111) surface by anchoring to C₆₀.     

SIMS accurate determination of matrix composition of topological crystalline insulator material Pb1 − xSnxSe

Substitutional alloy Pb_1 − xSn_xSe is a new class of electronic materials called topological crystalline insulators, which at the temperature range from 0 K to 300 K exhibit topological state at compositions in the range 0.18 < x < 0.40 (in the rock-salt structure). In this report, we present a secondary ion mass spectrometry (SIMS) analysis technique to provide accurate Pb and Sn composition based on the measurement of PbCs⁺ and SnCs⁺ cluster ions intensities. Studies of Pb_1 − xSn_xSe bulk samples with various values of x show that x/(1 − x) is linear in relation to the intensity ratio of PbCs⁺/SnCs⁺ over the range from x = 0.15 to x = 0.41. This technique allows us to obtain an accurate Sn content for multilayered heterostructures, quantum wells containing Pb_1 − xSn_xSe with different x values for each layer.     

Theoretical investigation of the molecular structure,vibrational spectra,and molecular docking of tramadol using density functional theory

The optimized molecular structures, harmonic vibrational wavenumbers, and the corresponding vibrational assignments of (1S,2S)-tramadol and (1R,2R)-tramadol are computationally examined using the B3LYP density functional theory method together with the standard 6–311++G(d,p) and def2-TVZP basis sets. The optimized structures show that phenolic rings of both 1R,2R and 1S,2S tramadol adopt planar geometry, which are slightly distorted due to the substitution at the meta-position; and the six-membered cyclohexane adopts a slightly distorted chair conformation. The 1S,2S enantiomer is energetically more favorable than 1R,2R with the energy differences of 1.32 and 1.03 kcal/mol obtained at B3LYP/6–311++G(d,p) and B3LYP/Def2-TVZP levels, respectively. The analysis of the binding pocket in the silico molecular docking with the m-opioid receptor shows that it originated two clusters with the 1S,2S enantiomer and one cluster with the 1R,2R enantiomer of tramadol. The results point to a more stable complex of the m-opioid receptor with the 1R,2R enantiomer of tramadol.     

The preparation,physicochemical and thermal properties of the high moisture,solvent and chemical resistant starch-g-poly(geranyl methacrylate) copolymers

Journal of Thermal Analysis and Calorimetry - The thermal properties together with the identification of the emitted volatiles during heating of the starch-graft-poly(geranyl methacrylate)...     

Aqueous extracts of Agave sisalana boles have prebiotic potential

Abstract

This work aimed at evaluating the prebiotic potential of the aqueous extract and crude polysaccharides from Agave sisalana boles by an in vitro screening. Crude polysaccharides were obtained from the aqueous bole extract by precipitation with acetone and resuspension in water. The liquid extract and the polysaccharide solution were then spray dried and submitted to thermal analysis and quantification of metabolites. Prebiotic activity was checked on probiotic strains belonging to the Lactobacillus genus using inulin, fructo-oligosaccharides, fructose and glucose as positive controls. The powder of A. sisalana bole extract, which has recently been identified as a rich source of inulin, exhibited higher potential of fermentation compared with crude polysaccharides.