Structural Determinants of the Selectivity of 3‐Benzyluracil‐1‐acetic Acids toward Human Enzymes Aldose Reductase and AKR1B10

The human enzymes aldose reductase (AR) and AKR1B10 have been thoroughly explored in terms of their roles in diabetes, inflammatory disorders, and cancer. In this study we identified two new lead compounds, 2‐(3‐(4‐chloro‐3‐nitrobenzyl)‐2,4‐dioxo‐3,4‐dihydropyrimidin‐1(2H)‐yl)acetic acid (JF0048, 3 ) and 2‐(2,4‐dioxo‐3‐(2,3,4,5‐tetrabromo‐6‐methoxybenzyl)‐3,4‐dihydropyrimidin‐1(2H)‐yl)acetic acid (JF0049, 4 ), which selectively target these enzymes. Although 3 and 4 share the 3‐benzyluracil‐1‐acetic acid scaffold, they have different substituents in their aryl moieties. Inhibition studies along with thermodynamic and structural characterizations of both enzymes revealed that the chloronitrobenzyl moiety of compound 3 can open the AR specificity pocket but not that of the AKR1B10 cognate. In contrast, the larger atoms at the ortho and/or meta positions of compound 4 prevent the AR specificity pocket from opening due to steric hindrance and provide a tighter fit to the AKR1B10 inhibitor binding pocket, probably enhanced by the displacement of a disordered water molecule trapped in a hydrophobic subpocket, creating an enthalpic signature. Furthermore, this selectivity also occurs in the cell, which enables the development of a more efficient drug design strategy: compound 3 prevents sorbitol accumulation in human retinal ARPE‐19 cells, whereas 4 stops proliferation in human lung cancer NCI‐H460 cells.     

Effect of Temperature on C3S and C3S + Nanosilica Hydration and C–S–H Structure

This study aimed to monitor the effect of temperature and the addition of nanosilica on the nanostructure of the C–S–H gel forming during tricalcium silicate (C₃S) hydration. Two types of paste were prepared from a synthesized T₁ C₃S. The first consisted of a blend of deionized water and C₃S at a water/solid ratio of 0.425. In the second, a 90 wt% C₃S + 10 wt% of nanosilica blend was mixed with water at a water/solid ratio of 0.7. The pastes were stored in closed containers at 100% RH and 25°C, 40°C, or 65°C. The hydration reaction was detained after 1, 14, 28, or 62 d with acetone, and then pastes were studied by ²⁹Si magic angle spinning nuclear magnetic resonance (²⁹Si MAS NMR).The main conclusion was that adding nSA expedites C₃S hydration at any age or temperature and modifies the structure of the C–S–H gel formed, two types of C–S–H gel appear. At 25°C and 40°C, more orderly, longer chain gels are initially (1 d) obtained as a result of the pozzolanic reaction between nSA and portlandite (CH) (C–S–H_II gel formation). Subsequently, ongoing C₃S hydration and the concomitant flow of dimers shorten the mean chain length in the gel.     

Integrated combined cycle from natural gas with CO2 capture using a Ca–Cu chemical loop

The integration in a natural gas combined cycle (NGCC) of a novel process for H₂ production using a chemical Ca–Cu loop was proposed. This process is based on the sorption‐enhanced reforming process for H₂ production from natural gas with a CaO/CaCO₃ chemical loop, but including a second Cu/CuO loop to regenerate the Ca‐sorbent. An integration of this system into a NGCC was proposed and a full process simulation exercise of different cases was carried out. Optimizing the operating conditions in the Ca–Cu looping process, 8.1% points of efficiency penalty with respect to a state‐of‐the‐art NGCC are obtained with a CO₂ capture efficiency of 90%. It was demonstrated that the new process can yield power generation efficiencies as high as any other emerging and commercial concepts for power generation from NGCC with CO₂ capture, but maintaining competing advantages of process simplification and compact pressurized reactor design inherent to the Ca–Cu looping system. © 2013 American Institute of Chemical Engineers AIChE J, 59: 2780–2794, 2013     

The steryl ester and phospholipid fatty acids of the spongeAgelas conifera from the Colombian Caribbean

The steryl ester and phospholipid fractions of the marine spongeAgelas conifera were isolated and analyzed. The fatty acyl components of the steryl ester and phospholipid fractions as determined by gas chromatography and gas chromatography/mass spectrometry were very similar and consisted of 56.8 and 62.7% of C₁₄−C₂₀ acids (normal; branched, especiallyiso andanteiso; and monounsaturated, particularly Δ⁹ and Δ¹¹ acids) and of 43.1 and 35.5% of C₂₄−C₂₆ acids (Δ^5,9 diunsaturated acids), respectively. The major constituent fatty acids detected were 13-methyltetradecanoic,n-hexadecanoic, 10-methylhexadecanoic, 11-octadecenoic, 12-methyloctadecanoic, 5,9-pentacosadienoic and 5,9-hexacosadienoic acids. The phospholipids isolated were identified as phosphatidylcholine (37%), phosphatidylserine (34%), phosphatidylethanolamine (16%) and phosphatidylinositol (11%). The distribution of fatty acids within the phospholipid classes was also determined.     

Temperature stimuli-responsive nanoparticles from chitosan-graft-poly(N-vinylcaprolactam) as a drug delivery system

This work describes the preparation of thermosensitive chitosan-graft-poly(N-vinylcaprolactam) nanoparticles by ionic gelation and their potential use as a controlled drug delivery system, using doxorubicin as a model drug. A systematic study of the effect of the main processing parameters on both the size and thermoresponsive behavior of nanoparticles was investigated. The size of the particles is strongly dependent on the length of the poly(N-vinylcaprolactam) grafted chains and the concentration of the copolymer and crosslinking agent solutions. The molecular structure of the copolymer plays an essential role in the phase transition temperature of the particles, which decreases with the length of PVCL grafted chain. The system displayed proper drug-association parameters, and the drug-loaded nanoparticles exhibited dose-dependent cytotoxicity. A significant increase in the doxorubicin delivery rate was observed above the phase transition temperature (40 °C). These features indicate that these nanoparticles are suitable for the development of a new thermally controlled anti-cancer drug delivery system. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47831.     

Avoiding structure degradation during activation of ordered mesoporous carbons

Hierarchical micro–mesoporous carbons with high porosity development and ordered structure were prepared. The innovative proposal consists in developing microporosity in ordered mesoporous carbon by chemical activation in template presence in order to minimize the structural damage. Thus, we have directly carried out the chemical activation of a mesoporous carbon/silica composite with KOH. The effect on mesoporous ordered structure of both KOH/carbon ratio and activation temperature has been studied. Following chemical activation the specific surface area is increased from 341 to 1757 m²/g and the micropore volume becomes almost six times larger than initial value. Although a slight widening of the mesopore distribution and an increase in the mesopore volume has been observed during activation, TEM and XRD results reveal an excellent conservation of the ordered mesoporous structure during activation even at conditions well above the limits that a CMK-3 type carbon can resist.     

Novel fatty acid esters of (7E, 12E, 18R, 20Z)-variabilin from the marine sponge Ircinia felix

The methanolic extract of the marine sponge Ircinia felix has yielded nine novel fatty acid esters, (7E, 12E, 18R, 20Z)-variabilin (5Z, 9Z)-22-methyltricosadienoate, (7E, 12E, 18R, 20Z)-variabilin (5Z, 9Z)-tetracosadienoate, (7E, 12E, 18R, 20Z)-variabilin hexadecanoate, (7E, 12E, 18R, 20Z)-variabilin 10-methylhexadecanoate, (7E, 12E, 18R, 20Z)-variabilin 15-methylhexadecanoate, (7E, 12E, 18R, 20Z)-variabilin 14-methylhexadecanoate, (7E, 12E, 18R, 20Z)-variabilin 9-octadecenoate, (7E, 12E, 18R, 20Z)-variabilin octadecanoate, and (7E, 12E, 18R, 20Z)-variabilin 2,11-dimethyloctadecanoate, along with the recently described (7E, 12E, 18R, 20Z)-variabilin 11-methyloctadecanoate. The characterization of the new fatty acids (5Z, 9Z)-22-methyltricosadienoic and 2,11-dimethyloctadecanoic acids is also described. The chemical structures were determined by extensive spectroscopic, chromatographic, and chemical analyses.     

Formation of biogenic amines throughout the industrial manufacture of red wine

Changes in biogenic amines (histamine, methylamine, ethylamine, tyramine, phenylethylamine, putrescine, and cadaverine) were monitored during the industrial manufacture of 55 batches of red wine. The origin of these amines in relation to must, alcoholic fermentation, malolactic fermentation, sulfur dioxide addition, and wine aging and the interactions between amines and their corresponding amino acids and pH were statistically evaluated in samples from the same batches throughout the elaboration process. Some amines can be produced in the grape or the musts (e.g., putrescine, cadaverine, and phenylethylamine) or can be formed by yeast during alcoholic fermentation (e.g., ethylamine and phenylethylamine), although quantitatively only very low concentrations are reached in these stages (less than 3 mg/liter). Malolactic fermentation was the main mechanism of biogenic amine formation, especially of histamine, tyramine, and putrescine. During this stage, the increase in these amines was accompanied by a significant decline in their amino acid precursors. Significant correlations between biogenic amine formation and the disappearance of their corresponding amino acids were observed, which clearly supports the hypothesis that malolactic bacteria are responsible for accumulation of these amines in wines. No increase in the concentration of biogenic amines was observed after SO2 addition and during wine aging, indicating that sulfur dioxide prevents amine formation in subsequent stages.     

TaqMan real-time PCR for the detection and quantitation of pork in meat mixtures

A rapid and highly specific real-time quantitative PCR, based on the amplification of a fragment of the mitochondrial 12S ribosomal RNA gene (rRNA), has been developed for the quantitation of pork (Sus scrofa) in binary pork/beef muscle mixtures. The method combines the use of pork-specific primers, that amplify a 411bp fragment from pork DNA, and mammalian-specific primers amplifying a 425-428bp fragment from mammalian species DNA, which are used as endogenous control. An internal fluorogenic probe (TaqMan), that hybridizes in the "pork-specific" and also in the "mammalian" DNA fragments is used to monitor the amplification of the target gene. A comparison of the cycle number (C(t)) at which mammalian and pork-specific PCR products are first detected, in combination with the use of reference standards of known pork content, allows the determination of the percentage of pork in a mixed sample. Analysis of experimental pork/beef muscle binary mixtures demonstrated the specificity and sensitivity of the assay for detection and quantitation of pork in the range 0.5-5%.