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4-Quinolones compose a remarkable class of compounds that show various pharmacological applications. In particular, the activities of both (S) and (R) enantiomers of 2-aryl-2,3-dihydro-4(1H)-quinolones have made them an object of befitting interest for asymmetric synthesis. Although readily yielded as a racemic mixture from an one-pot reaction between 2-aminoacetophenone and benzaldehyde, a pathway for the metal-free enantioselective one-pot synthesis of the (S) isomer is not completely clear. In the present work, guided by the burgeoning role of organocatalysis in asymmetric synthesis and recent experimental insight into the most likely reaction mechanism, we report the in silico screening for a roster of MacMillan chiral imidazolidinones through quantum mechanics calculations. Two stereopredictive models yielding similarly high expected ee (up to 97%) were proposed. The role of aromatic interactions for the control of enantioselectivity was systemically studied, as well as the Pro-S si-enantiofacial attack activation energies, which were found to correlate well (R2 = 0.75) with the reported Bürgi-Dunitz angle for the expected intramolecular Mannich reaction mechanism.
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Quinolonas , Catálisis , EstereoisomerismoRESUMEN
In the 1950s, Alan Turing showed that concerted reactions and diffusion of activating and inhibiting chemical species can autonomously generate patterns without previous positional information, thus providing a chemical basis for morphogenesis in Nature. However, access to these patterns from only one molecular component that contained all the necessary information to execute agonistic and antagonistic signaling is so far an elusive goal, since two or more participants with different diffusivities are a must. Here, we report on a single-molecule system that generates Turing patterns arrested in the solid state, where supramolecular interactions are used instead of chemical reactions, whereas diffusional differences arise from heterogeneously populated self-assembled products. We employ a family of hydroxylated organic salphen building blocks based on a bis-Schiff-base scaffold with portions responsible for either activation or inhibition of assemblies at different hierarchies through purely supramolecular reactions, only depending upon the solvent dielectric constant and evaporation as fuel.
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The importance of gem-difunctionalized ketones is represented by their broad applications across chemical boundaries over recent years. The interesting reactivities that this class of compounds possess have made them ideal building blocks to access high-value organic molecules. Furthermore, the gem-difunctionalized ketone moiety has featured in numerous bioactive molecules. For these reasons, a plethora of routes to access such significant molecules have been developed by research groups worldwide - this account looks at delineating the synthesis of gem-difunctionalized ketones from carbonyl substrates, diazo compounds, sulfur ylides and alkynyl reactants.
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The study aimed to include the isolated vitexin of Jatropha mutabilis in the ß-cyclodextrin cavity to improve the solubility of this flavone. Its characterization was performed by techniques such as 1H NMR/ROESY (Nuclear Magnetic Resonance Spectroscopy), FT-IR (Infrared Spectroscopy with Fourier Transform), SEM (Morphological analysis of IC by Scanning Electron Microscopy) and dissolution study in vitro. In addition, the following activities were evaluated in the animal models: expectorant, phenol red dosage in bronchoalveolar lavage and antitussive, cough induced by citric acid. In the characterization of the complex, interaction between hydrogens of ring B of vitexin and (H3) of ß-CD was observed, in addition to changes in morphology. In the dissolution test, an increase in the rate of dissolution of vitexin was observed in the first 30 min for the CI vitexin/ß-CD when compared with vitexin. Regarding the pharmacological activity, it was observed that the inclusion complex (IC) vitexin/ß-CD in the equivalent doses of 0.2, 1 and 5 mg/kg of flavone presented higher expectorant activity when compared to vitexin (p < 0.05), suggesting increased bioavailability. As for the antitussive activity, both vitexin and the complex had similar effects and were dose independent. In the toxicity test using Artemia salina, vitexin and IC vitexin/ß-CD were considered non-toxic. At last, the study efficacy of vitexin/ß-CD IC as an expectorant and of vitexin as antitussive. All of these data are being described for the first time.
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The aromatic nucleophilic substitution reactions of the nitro group of 4-Nitro-N-alkyl-1,8-naphthalimides by thiolate anions produce fluorescent derivatives and their rates are strongly accelerated by micelles of hexadecyltrimethylammonium chloride even at low pH. Acceleration factors of this reactions can reach million-fold. As the products are oxidant-insensible, this reaction allows the determination of SH- containing compounds such as cysteine, glutathione or proteins even in oxidative conditions. Limits of detection are as low as 5 × 10-7 M, ten times lower than the limit for the classic 5,5'-dithiobis-(2-nitrobenzoic) acid method. Moreover, this reaction can be developed at pHs between 6.5 and 7.5 thereby diminishing the rate of spontaneous oxidation of the thiols. In addition, we demonstrated that 4-Nitro-N-alkyl-1,8-naphthalimides can be used to evidence SH groups in peptides, proteins and living cells.
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The presence of internal rotation in sigma bonds is essential for conformational analysis of organic molecules and its understanding is of great relevance in chemistry, as well as in several other areas. However, for aromatic compounds that have substituent groups, withdrawers or donors of electron, there are no data in the literature to explain their rotational barriers. In this context, the work studied the internal rotational barriers of electron donating and withdrawing groups in aromatic compounds using the MP3, MP4, and CCSD(T) methods and the influence of substituents' nature on barrier heights was investigated through calculations based on the theory of Natural Bond Orbitals (NBO) and Quantum Theory of Atoms in Molecules (QTAIM). The results obtained showed that the CCSD(T) method is the one that best describes the internal rotational barriers, followed by MP4 and MP3 and the electron donating groups decrease the barrier, whereas electron withdrawing groups increase. Through the NBO analysis it was possible to observe that for withdrawing groups the interaction of the molecular orbitals is more accentuated promoting the increase of the rotational barrier of these compounds. Through the QTAIM analysis it was possible to show that, for electron donating groups, the internal rotation is influenced by the loss of electronic density when the substituents is perpendicular to the ring plane, however, for withdrawing groups the density is little influenced, regardless of the two conformations (minimum and maximum energy). Two molecules showed free rotation, trichloromethylbenzene and methylbenzene, and the theoretical calculations NBO and QTAIM showed that for these species there is no difference in the properties studied when there is rotation of the dihedral angle.
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Turpentine is a mixture of monoterpene hydrocarbons obtained as a by-product in the paper industry. In this contribution we present its transformation process towards an alcohol named nopol, that is an important household product and fragrance raw material. Reaction conditions were established for the oxyfuntionalization of crude turpentine oil over Sn-MCM-41 catalyst for the selective conversion of ß-pinene to nopol. Synthesized materials were characterized by XRD, N2 adsorption, FT-IR, TEM and chemical absorption. The reaction was tested in 2 mL glass reactor with a sample of commercial turpentine with α-pinene (55.5% w/w) and ß-pinene (39.5% w/w) as main components and scaled up into a 100 mL Parr reactor, getting 92% conversion of ß-pinene and a nopol selectivity of 93%. The reusability tests showed that the catalyst can be reused 4 times without loss of activity. The results showed that 86% less solvent and 37.5% less paraformaldehyde can be used with turpentine, compared to the conditions used with ß-pinene for getting similar catalysts activity.
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Gold honey variety pineapple wastes and sacha inchi sub-products (SIS) were characterized in their elemental, physical, and chemical form in order to formulate a supplemented fermentation substrate (SFS) for the growth Weissella cibaria. The peels and fresh cores of the pineapple (FPP, FPC) were dried and ground (PPP, PPC) and then mixed (MCPP). The following procedures were then undertaken: a physicochemical characterization (moisture, aw, pH, acidity, and soluble solids) of the SIS, FPP, FPC, PPP, and PPC; a proximal characterization of he FPP, FPC, SIS, and SFS; and an elemental analysis (C-N2-H2-O2-S) of the MCPP, SIS, and W. cibaria, which allowed the stoichiometric equation to be defined and the SFS to be formulated. We then evaluated the effect that homogenization and heating to boiling point had on the concentration of reducing sugars in the SFS (g L-1). Finally, W. cibaria´s kinetic fermentation parameters were evaluated in the SFS and in a commercial substrate (control). The results showed FPP and FPC yields of 26.02 ± 0.58 and 14.69 ± 1.13%, respectively; a higher total sugar content in FPC (7.21%) than in FPP (6.65%); a high crude protein content in SIS (56.70%), and a C:N2 ratio of 6.50:1.00. Moreover, the highest concentration of reducing sugars (4.44 ± 0.29 g L-1) in the SFS was obtained with 5 h of hydrolysis under homogenization pre-treatments and heating until boiling. The SFS allowed the adaptation of W. cibaria, and there was a biomass production of 2.93 g L-1 and a viability of 9.88 log CFU mL-1. The formulation of an unconventional fermentation substrate from -Agro-industrial wastes of pineapple and sacha inchi to produce valuable products (such as lactic acid biomass through fermentation), is an excellent perspective for large-scale application.
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In this study, we report our contribution to the application of the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction for the synthesis of ß-keto-1,2,3-triazole derivatives 3a-f from ethinylestradiol and their application in the inhibition of two human cancer cells lines: human breast adenocarcinoma (MCF-7) and human hepatocellular carcinoma (HepG2). The ß-keto-1,2,3-triazole derivates 3a-f exhibited moderate cytotoxic activity for the HepG2 cells with IC50 values of 29.7 µM (3a), 16.4 µM (3b), 17.8 µM (3c), 20.4 µM (3d), 28.1 µM (3e) and 28.2 µM (3f). The semi-synthetic ß-keto-1,2,3-triazoles derivatives 3a-f were all characterized by FT-IR, NMR, HRMS and [α]D.
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A methodology based on the concepts that arise from Density Functional Theory (CDFT) was chosen for the calculation of the global and local reactivity descriptors of the Phallotoxin family of fungal peptides. The determination of the active sites for the molecules has been achieved by resorting some descriptors within Molecular Electron Density Theory (MEDT) like the Dual Descriptor and the Parr functions. Phallosacin has been found as the most reactive of the peptides on the basis of the calculated Global Reactivity Descriptors. The pKas of the seven studied peptides were established using a proposed relationship between this property and the calculated Global Hardness. The bioactivity properties of the peptides considered in this study were obtained by resorting to a homology model by comparison with the bioactivity of related molecules in their interaction with different receptors.
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New N-propargyl tetrahydroquinolines 6a-g have been synthesized efficiently through the cationic Povarov reaction (a domino Mannich/Friedel-Crafts reaction), catalyzed by Indium (III) chloride (InCl3), from the corresponding N-propargylanilines preformed, formaldehyde and N-vinylformamide, with good to moderate yields. All tetrahydroquinoline derivatives obtained were evaluated in vitro as free radical scavengers. Results showed that compound 6c presents a potent antioxidant effect compared with ascorbic acid, used as a reference compound. ADME predictions also revealed favorable pharmacokinetic parameters for the synthesized compounds, which warrant their suitability as potentials antioxidant. Additionally, a theoretical study using Molecular Quantum Similarity and reactivity indices were developed to discriminate different reactive sites in the new molecules in which the oxidative process occurs.
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In this work, 8 samples of carbon aerogels with different ratios of catalyst versus resorcinol (R/C) from 25 to 1500 were used. The textural properties were evaluated from N2 adsorption isotherms in 77 K, as well as the chemical ones, where the surface chemistry was evaluated through the Boehm titrations. The results were analyzed and related to the adsorption of the nickel (II) ion from aqueous solution. The experimental results show that the aerogel samples can be divided into two series with different properties: Series I, mainly microporous (low ratio R/C) and Series II (high ratio R/C) mainly microporous but with a contribution of mesoporosity. The specific surface area varied between 64 and 990 m2 g-1. The experimental results show that prepared aerogels have an adequate adsorption capacity towards nickel (II) ions. The behavior of the kinetics of Ni(II) adsorption on carbon aerogels adjusts in a better way the kinetic model of pseudo-second order since it is the one that presents the value of the highest R2 correlation coefficient. The calorimetric data shows that the greater the area developed in carbons aerogels the enthalpy increases.
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Two catalysts were prepared using monodisperse pre-synthetized nanoparticles of metallic nickel and nickel phosphides with the same average diameter. Both nanoparticles species were deposited on the same support: mesoporous silica nano-spheres of MCM-41. This support is suitable to inhibit agglomeration and sintering processes during preparation steps. Therefore, two supported and activated catalysts with the same average nanoparticles diameter were obtained. They differ only in the nature of the active species: metallic nickel and nickel phosphides. The effect of the presence of a second element (phosphorus), more electronegative than nickel, on the activity and selectivity in the chemoselective hydrogenation of acetophenone was studied. The reaction conditions were: H2 pressure of 1 MPa, 80 °C using n-heptane as solvent. With the aim to understand the catalytic results, nanoparticles, support and catalysts were carefully characterized by X-ray diffraction, diffuse light scattering, transmission electron microcopy, high resolution transmission electron microcopy, selected area electron diffraction, scanning electron microcopy, Fourier transformer infrared spectroscopy, N2 adsorption at -196 °C, atomic absorption, H2 and CO chemisorption and volumetric oxidation. Considering these results and geometric and electronic characteristics of the surface of both active species, a change in the adsorption intermediate state of acetophenone in presence of phosphorus is proposed to explain the hydrogenation chemoselectivity of nickel phospides.
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Poly(amidoamine) and Poly(propylenimine) dendrimers with different generations and peripheral groups were studied as solubility enhancers and nanocarriers for 7-bromo-2-hydroxy-phenazine N 5,N 10-dioxide. This compound possesses potential antitumoral and anti-trypanosomal activity, but its low solubility in physiological media precludes its possible application as therapeutic drug. The amino terminated dendrimers association with the active compounds as observed trough NMR studies showed that electrostatic interactions are essential in the solubilization enhancement process. The obtaining of a stable and no cytotoxic formulation makes the drug-carried association a suitable strategy for the generation of a drug delivery system for phenazine derivatives.
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The present study evaluates biosorption efficiencies of pesticides atrazine, fluazifop-P-butyl, lactofen, lambda-cyhalothrin and chloropyrifos on corks of Quercus cerris and Quercus suber trees. The studies were carried out in batch and effects of pH (3, 7 and 9), temperature (10, 20, 30 and 40 °C), and time on adsorption were measured. Pesticide analyzes were performed with an Ion-trap Mass Spectrometer following the SANCO/10232/2006 EU extraction protocol for pesticides. The results show that the highest adsorption efficiency (80% and 70%) of the pesticides was found at pH 3, 30 °C and 360 minutes. The adsorption kinetics of pesticides followed pseudo-second order and pseudo-first order kinetics. The results obtained in this study show that Q. cerris and Q. suber corks can be used to develop efficient and economical cork-based alternatives for the treatment of environments contaminated with pesticides.
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Two solvent free methods of a one-to-one alcohol/acid mol ratio synthesis of benzyl esters of the formic, acetic, benzoic, salicylic, nicotinic, and oxalic acids are described. The stoichiometric reactions used 1.5 mol ratio solid NbCl5 as the reagent and required from two to three hours for completion at room temperature; for the catalytic processes, NbCl5 was grafted directly, at room temperature, onto a silica gel of specific area of 507 m2g-1, produced from construction sand and sodium carbonate, forming a 5.4% Nb w/w SiO2-Nb gel with a specific area of 412 m2g-1. At 10% w/w catalyst/alcohol ratio, this SiO2-Nb catalyst gave similarly very good yields but required from 6 to 9 hours at the reflux temperature of the slurry. The catalyst could be re-used three times.
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Leishmaniasis and Chagas disease are endemic pathologies in tropical countries. These cause high morbidity and a public health problem. Current chemotherapies are based on conventional drugs with variable efficacy and toxicity related with the length of therapeutic schemes and high doses. When two pharmacological agents are combined into a single molecule, the result is the so-called hybrid molecule. In the search for new treatments against Chagas disease and leishmaniasis, several studies have shown that hybrid molecules display high antiprotozoal activity and this emerging strategy is quite promising in the field of new drug discovery and development. This review focuses on the antiprotozoal activity of different hybrids obtained from the hybridization of pharmacophores, showing that the most of the efforts have been concentrated in the molecular hybridization of quinoline, chalcone and hydrazone moieties.
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Antiprotozoarios/uso terapéutico , Enfermedad de Chagas/tratamiento farmacológico , Leishmaniasis/tratamiento farmacológico , Antiprotozoarios/química , Antiprotozoarios/farmacología , Enfermedad de Chagas/patología , Chalcona/química , Humanos , Hidrazonas/química , Leishmaniasis/patología , Pentamidina/química , Quinolinas/química , Terpenos/química , Triazoles/químicaRESUMEN
The discovery of the importance of kinase activity and its relationship to the emergence and proliferation of cancer cells, due to changes in normal physiology, opened a remarkable pathway for the treatment of chronic myelogenous leukemia through intense search of drug candidates. Six Abl kinase inhibitors have received the US FDA approval as chronic myelogenous leukemia treatment, and continuous efforts in obtaining new, more effective and selective molecules are being carried out. Herein we discuss the mechanisms of Abl inhibition, structural features and ligand/protein interactions that are important for the design of new Abl kinase inhibitors. This review provides a broad overview of binding mode predictions, through molecular docking, which can be an approach to discover novel Abl kinase inhibitors.
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Esta investigación tiene un doble propósito, en primer lugar, valorar las actitudes hacia la química de alumnos universitarios de carreras biológicas en dos cursos relacionados con esta disciplina y, por otro lado, relacionar dichas actitudes con el rendimiento académico presentado por los estudiantes. El instrumento elegido para medir las actitudes de los alumnos fue un cuestionario según la escala Likert, encuestándose a la totalidad de estudiantes que cursaban cada uno de los cursos de química analizados: Química General e Inorgánica (QGI) y Química Orgánica (QO). Para estimar el rendimiento académico se analizaron actas de parciales y se realizaron cálculos de correlación. Los alumnos que cursaban QGI presentaron actitudes hacia la química valoradas como indiferentes. Sin embargo al finalizar el curso de QO sus actitudes fueron evolucionando favorablemente, ya que la puntuación media obtenida para los ítems positivos y negativos estuvo en el rango de actitudes positivas. Los valores del coeficiente de Pearson obtenidos para los dos cursos estudiados fueron superiores a 0,80, lo que indica una fuerte relación entre las variables implicadas, por lo cual se infiere la importancia de desarrollar actitudes positivas hacia la química para favorecer el rendimiento académico de los alumnos.
This work has a double aim, in the first place, to value the attitudes towards the chemistry of university students of biological careers in two courses related to this discipline and, on the other hand, to relate these attitudes to the academic yield presented by the students. The chosen instrument to measure the attitudes of the students was a questionnaire according to the Likert scale; the totality of students who attended each one of the analyzed courses of chemistry, General and Inorganic Chemistry (QGI) and Organic Chemistry (QO), were polled. In order to consider the academic yield, proceedings of midterms were analyzed and calculations of correlation were made. The students who attended QGI presented attitudes towards chemistry valued like indifferent. Nevertheless, at the end of QO attitudes of students were evolving favorably, since the obtained average score for the positive and negative items was in the rank of positive attitudes. The values of the obtained coefficient of Pearson for both courses studied were superior to 0.80, which indicates a strong relation between the implied variables. Whereby, it follows the importance of developing positive attitudes towards chemistry to favor the academic yield of the students.
Esta pesquisa tem um duplo propósito, antes de tudo, medir atitudes em relação a química de estudantes universitários em ciências biológicas, em dois cursos relacionou-se a esta disciplinae, em seguida, relacionar estas atitudes ao desempenho académico apresentou-se pelos estudantes. O instrumento escolhido para medir as atitudes dos estudantes era um questionário de acordo com a escala de Likert, encuestando próprio ao totalidade dos estudantes que atenderam a cada dos cursos analisados do quimica: Quimica Geral e Inorgánica (QGI) e Química Orgánica (QO). Para considerar os atos académicos do rendimento os registos dos exames foram analisados e os cálculos da correlação foram feitos. Os estudantes que atenderam a QGI apresentaram-se atitudes indicados para o química avaliado como indiferente. Não obstante quando finalizar atendido de QO suas atitudes estava evoluindo favoràvel, desde que a contagem média obtida para os artigos positivos e negativos estava na gama de atitudes positivas. Os valores do coeficiente obtido de Pearson para ambos cursos estudados eram superiores a 0.80, indicando uma relação forte entre as variáveis implicadas; pelo que pode-se inferir a importância de desenvolver atitudes positivas para a química para favorecer o rendimento académico dos estudantes.