Synthesis of Novel Methyl 7-[(Hetero)arylamino]thieno[2,3-b]pyrazine-6-carboxylates and Antitumor Activity Evaluation: Effects in Human Tumor Cells Growth,Cell Cycle Analysis,Apoptosis and Toxicity in Non-Tumor Cells

Several novel methyl 7-[(hetero)arylamino]thieno[2,3-b]pyrazine-6-carboxylates were synthesized by Pd-catalyzed C–N Buchwald–Hartwig cross-coupling of either methyl 7-aminothieno[3,2-b]pyrazine-6-carboxylate with (hetero)arylhalides or 7-bromothieno[2,3-b]pyrazine-6-carboxylate with (hetero)arylamines in good-to-excellent yields (50% quantitative yield), using different reaction conditions, namely ligands and solvents, due to the different electronic character of the substrates. The antitumoral potential of these compounds was evaluated in four human tumor cell lines: gastric adenocarcinoma (AGS), colorectal adenocarcinoma (CaCo-2), breast carcinoma (MCF7), and non-small-cell lung carcinoma (NCI-H460) using the SRB assay, and it was possible to establish some structure–activity relationships. Furthermore, they did not show relevant toxicity against a non-tumor cell line culture from the African green monkey kidney (Vero). The most promising compounds (GI₅₀ ≤ 11 µM), showed some selectivity either against AGS or CaCo-2 cell lines without toxicity at their GI₅₀ values. The effects of the methoxylated compounds 2b (2-OMeC₆H₄), 2f and 2g (3,4- or 3,5-diOMeC₆H₃, respectively) on the cell cycle profile and induction of apoptosis were further studied in the AGS cell line. Nevertheless, even for the most active (GI₅₀ = 7.8 µM) and selective compound (2g) against this cell line, it was observed that a huge number of dead cells gave rise to an atypical distribution on the cell cycle profile and that these cells were not apoptotic, which points to a different mechanism of action for the AGS cell growth inhibition.     

Finest Morse Decompositions for Semigroup Actions on Fiber Bundles

Let S{\mathcal{S}} be a semigroup acting on a topological space M. We study finest Morse decompositions for the action of S{\mathcal{S}} on M. This concept depends on a family of subsets of S{\mathcal{S}} . For certain semigroups and families it recovers the concept of Morse decomposition for flows and semiflows. This paper also studies the behaviour of Morse decompositions for semigroup actions on principal bundles and their associated bundles. The emphasis is put on the study of those decompositions considering their projections onto the base space and their intersections with the fibers.     

Brans-dicke vacuum solutions and the cosmological constant: A qualitative analysis

We investigate Brans-Dicke vacuum solutions in the presence of a cosmological constant A from the point of view of dynamical system theory. Assuming a Friedmann-Robertson-Walker metric we plot the phase diagrams corresponding to all values of. The analysis of the diagrams allows us to determine several physical properties of the solutions as well as their global dynamical behaviour.     

Quantification of organic acids in beer by nuclear magnetic resonance (NMR)-based methods

The organic acids present in beer provide important information on the product's quality and history, determining organoleptic properties and being useful indicators of fermentation performance. NMR spectroscopy may be used for rapid quantification of organic acids in beer and different NMR-based methodologies are hereby compared for the six main acids found in beer (acetic, citric, lactic, malic, pyruvic and succinic). The use of partial least squares (PLS) regression enables faster quantification, compared to traditional integration methods, and the performance of PLS models built using different reference methods (capillary electrophoresis (CE), both with direct and indirect UV detection, and enzymatic essays) was investigated. The best multivariate models were obtained using CE/indirect detection and enzymatic essays as reference and their response was compared with NMR integration, either using an internal reference or an electrical reference signal (Electronic REference To access In vivo Concentrations, ERETIC). NMR integration results generally agree with those obtained by PLS, with some overestimation for malic and pyruvic acids, probably due to peak overlap and subsequent integral errors, and an apparent relative underestimation for citric acid. Overall, these results make the PLS-NMR method an interesting choice for organic acid quantification in beer.     

Mechanism of 1,4,5,8-naphthalene tetracarboxylic acid dianhydride hydrolysis and formation in aqueous solution

The study of highly conjugated, carbonyl-containing molecules such as 1,4,5,8-naphthalene tetracarboxylic dianhydride, III, is of interest since reactivity differences and transmission of electronic effects through the conjugated framework can be evidenced. The kinetics of hydrolysis of III in aqueous solution were determined from 5 M acid to pH 10. In basic solution hydrolysis of III yields, sequentially, 1,4,5,8-naphthalene diacid monoanhydride, II, and 1,4,5,8-naphthalene tetracarboxylic acid, I. The second order rate constant for alkaline hydrolysis is 200 fold higher for the first ring opening. The water-catalyzed hydrolysis of III yields a pH-dependent mixture of ionic forms of I and II. The rate constant for water-catalyzed hydrolysis of III is 25 fold higher than that for II. In concentrated acid the rates for reaching equilibrium (I, II and III) increase and III is the major product. The pK(a)s of I (3.24, 5.13 and 6.25) and II (3.05, 5.90) were determined by potentiometric, fluorescence and UV spectroscopy titrations and by quantitative fit of the kinetic and equilibrium data. The apparent, pH-dependent, equilibrium constants, K(EqII), for anhydride formation between I and II were obtained from the UV spectra. The quantitative fit of kinetic and equilibrium data are consistent with the assumption that anhydride formation only proceeds with the fully protonated species for both I and II and permitted the estimation of the equilibrium constants for anhydride formation, K(EqII). The value of K(EqII) (I <==> II) between pH 1 and 6 was ca. 5. Geometry optimization calculations in the gas phase of the reactions of III in alkaline, neutral and acid conditions, at the DFT level of theory, gave electronic distributions that were qualitatively consistent with the experimental results.     

Violation of bell's inequalities with a local theory of photons

We use a local theory of photons purely as particles to model the single-photon experiment proposed by Tan, Walls, and Collett. Like Tanet al. we are able to derive a violation of Bell's inequalities, but our local probabilistic theory does not use any specific quantum mechanical assumptions or calculations.     

A Comparative Study of Chemical Routes for Coating Gold Nanoparticles via Controlled RAFT Emulsion Polymerization

The synthesis of core‐shell Au nanoparticles protected by an amphiphilic block copolymer is investigated by distinct reversible addition fragmentation chain transfer (RAFT) emulsion polymerization routes. The controlled polymerization of polymer shells onto Au nanoparticles is attempted by using the macroRAFT (MR) agent based on 2‐(dodecylthiocarbonothioylthio)‐2‐methylpropionic acid synthesized via RAFT polymerization of poly(ethylene glycol) methyl ether acrylate and exploring several approaches, which include (i) post‐modification; (ii) in situ synthesis and (iii) “grafting from” strategies. In the conditions investigated here all these strategies lead to Au polymer nanocomposites but morphological well‐defined core‐shell nanoparticles are only obtained by applying the “grafting from” strategy. In particular, conditions that promote chain extension from the MR agent adsorbed onto the Au nanoparticles are found necessary to obtain nanostructures with such morphological characteristics and that still show the localized surface plasmon resonance typical of colloidal Au nanoparticles.     

Spectroscopic studies of the intermolecular interactions of Congo red and tinopal CBS with modified cellulose fibers

The adsorption of Congo red and tinopal CBS dyes on cellulose fibers was investigated using electronic absorption and fluorescence spectroscopies. Hydrogen bonds appear to be relevant for the dye-fiber interactions as indicated by the solvatochromism of Congo red in water, methanol, and dimethyl sulfoxide solutions, and when adsorbed on cellulose fibers. We also demonstrate that electrostatic interactions play an important role in the dye-medium interaction, through the analysis of absorption spectra of Congo red and fluorescence spectra of tinopal in aqueous solutions containing salt and in layer-by-layer nanostructured films with poly(allylamine hydrochloride). For instance, dye adsorption was enhanced when salt was added to the dipping solution, which was explained by the synergistic effect between the conformational changes of the cellulose and changes in the solvation layer around the cellulose chains and around dye molecules. On the basis of the fluorescence results for tinopal CBS, we inferred that dye aggregation is not relevant for adsorption on the fibers. In addition, fluorescence spectroscopy is proven very sensitive for studying the organization of dye molecules in layer-by-layer films, particularly those undergoing irreversible structural changes.     

On the Maximum Concentration of Contaminants in Natural Aquifers

We examine the temporal evolution of the maximum concentration of a dissolved inert solute in spatially heterogeneous subsurface flows. The maximum concentration of a given substance is at the basis of most of environmental regulatory practices where maximum tolerable levels of concentration are typically prescribed for a variety of known contaminants. Through the use of the Lagrangian framework, we elaborate over a physically based, semi-analytical model for the maximum concentration. Specifically, we address how the maximum concentration is affected by key geostatistical parameters (i.e., logconductivity variance), local-scale dispersion processes and engineering design variables such as the dimensions of the solute injection zone. The model will help in identifying the major components that determine the maximum concentration, which is important in order to better allocate resources toward site characterization and reduce uncertainty in predictions. The ultimate scope is to provide a theoretical framework that is application-oriented to estimate the maximum concentration in natural aquifers and provide some guidance in applications. It also provides an useful tool for preliminary, screening analysis and testing scenarios. We test the performance of the model against the MADE transport experiment, with reasonably good agreement.

     

Zeno effect in quantum Newton's cradle

We describe a chain of quantum oscillators which behaves analogously to Newton's cradle. The energy swings between the ends of the chain with very low population in its interior. Moreover, the oscillators at the ends can entangle with each other with negligible entanglement with the intermediate oscillators that mediate the process. Up to a certain number of oscillators, the system evolves in a manner similar to two coupled oscillators. The conditions for such behavior and the characteristic periods are analyzed. When that number exceeds a threshold, the dynamical regime changes to virtually freezing. In the oscillatory regime, Zeno effect can be observed. The parallelism between the Zeno dynamics in quantum Newton's cradle and in two coupled oscillators is highlighted. Promising platforms to observe such phenomena in the laboratory are cavities in photonic-band-gap material and trapped ions.