Nickel(II)-Catalyzed Formal [3+2] Cycloadditions between Indoles and Donor-Acceptor Cyclopropanes.

This article describes the development of a nickel-catalyzed regio- and diastereoselective formal [3+2] cycloaddition between N-substituted indoles and donor-acceptor cyclopropanes to synthesize cyclopenta[b]indoles. Optimized reaction conditions provide the desired nitrogen-containing cycloadducts in up to 93% yield and dr 8.6:1 with complete regioselectivity. The substrate scope showed high tolerance to various substituted indoles and cyclopropanes, resulting in the synthesis of six new cyclopenta[b]indoles and the isolation of five derivatives previously reported in the literature. In addition, a mechanistic proposal for the reaction was studied through online reaction monitoring by ESI-MS, allowing for the identification of the reactive intermediates in the Ni(II) catalyzed process. X-ray crystallography confirmed the structure and relative endo stereochemistry of the products. This method enables the fast and efficient construction of fused indolines from readily accessible starting materials.

Air-Stable Cobalt(III) and Chromium(III) Complexes as Single-Component Catalysts for the Activation of Carbon Dioxide and Epoxides.

Cobalt(III) and chromium(III) salophen chloride complexes were synthesized and tested for the cycloaddition of carbon dioxide (CO2) with epoxides to obtain cyclic carbonates. The cat1, cat2, cat4, and cat5 complexes presented high catalytic activity without cocatalysts and are solvent-free at 100 °C, 8 bar, and 9 h. At these conditions, the terminal epoxides (1a-1k) were successfully converted into the corresponding cyclic carbonates with a maximum conversion of ∼99%. Moreover, cat5 was highlighted due to its capability of opening internal epoxides such as limonene oxide (1l) with a 36% conversion to limonene carbonate (2l), and from cyclohexene oxide (1m), cyclic trans-cyclohexene carbonate (2m) and poly(cyclohexene carbonate) were obtained with 15% and 85% selectivity, respectively. A study of the coupling reaction mechanism was proposed with the aid of electrospray ionization mass spectrometry (ESI-MS) analysis, confirming the single-component behavior of the complexes through their ionization due to epoxide coordination. In addition, crystallographic analysis of cat1 single crystals grown in a saturated solution of pyridine helped to demonstrate that the substitution of chloride ion by pyridine ligands to form an octahedral coordination occurs (Py-cat1), supporting the proposed mechanism. Also, a recyclability study was performed for cat5, and a total turnover number of 952 was obtained with only minor losses in catalytic activity after five cycles.

Biopolymer-Based Composite Hydrogels Embedding Small Silver Nanoparticles for Advanced Antimicrobial Applications: Experimental and Theoretical Insights.

In this work, we report a two-step methodology for the synthesis of small silver nanoparticles embedded into hydrogels based on chitosan (CS) and hydroxypropyl methylcellulose (HPMC) biopolymers. This method uses d-glucose as an external green reducing agent and purified water as a solvent, leading to an eco-friendly, cost-effective, and biocompatible process for the synthesis of silver nanocomposite hydrogels. Their characterization comprises ultraviolet-visible spectroscopy, Fourier-transform infrared spectra, differential scanning calorimetry, scanning electron microscopy with energy-dispersive spectroscopy, and transmission electron microscopy assays. Moreover, the structural stability of the hydrogels was investigated through sequential swelling-deswelling cycles. The nanomaterials showed good mechanical properties in terms of their structural stability and revealed prominent antibacterial properties due to the reduced-size particles that promote their use as new advanced antimicrobial agents, an advantage compared to conventional particles in aqueous suspension that lose stability and effectiveness. Finally, theoretical analyses provided insights into the possible interactions, charge transfer, and stabilization process of nanoclusters mediated by the high-electron-density groups belonging to CS and HPMC, revealing their unique structural properties in the preparation of nano-scaled materials.

Enantioselective Imine Reduction of Dihydro-ß-carbolines by Fe-Thiosquaramide Catalyst.

Enantioselective imine reduction of dihydro-ß-carbolines (DHBCs) is a reliable and powerful tool to construct bioactive chiral tetrahydro-ß-carbolines (THBCs). Here, we report an efficient enantioselective imine reduction employing in situ generated Fe-thiosquaramides (Fe-TSQs) 3a and 3b as asymmetric organometallic catalysts to produce chiral THBCs (2a-h). The catalyst 3a at 15 mol % was found to be suitable for the substrates with alkyl and aryl groups which afford corresponding chiral THBCs with excellent enantioselectivities (up to ee 99%).

Salivary proteome of aphthous stomatitis reveals the participation of vitamin metabolism, nutrients, and bacteria.

There are currently no preventative options for recurrent aphthous stomatitis, and the only available treatments are palliative. This is partly due to a poor understanding of its etiopathogenesis. In this case-control study, we characterized the salivary proteome of patients with recurrent aphthous stomatitis in the presence and absence of lesions. Through mass spectrometry-based proteomics and bioinformatics tools, we identified that the presence of oral ulcers is associated with several specific biological processes, including the metabolic pathways of vitamin B9, B12, nitrogen, selenium, and the bacterium Neisseria meningitidis. These changes occurred only in the presence of clinically visible lesions, and there were no relevant differences between patients in anatomical regions unaffected by ulcers. Additionally, using western blot and ELISA assays, we verified that carbonic anhydrase 1 (CA1) and hemoglobin subunit beta (HBB) proteins are highly expressed during the ulcerative and remission phases of recurrent aphthous stomatitis. Our results cumulatively support saliva as an indicator of the pathophysiological changes, which occur during the clinical course of lesions. From a clinical perspective, we suggest that recurrent aphthous stomatitis is a condition triggered by temporary biological changes in people with lesions.

TCCA-mediated oxidative rearrangement of tetrahydro-ß-carbolines: facile access to spirooxindoles and the total synthesis of (±)-coerulescine and (±)-horsfiline.

Multi-reactive centered reagents are beneficial in chemical synthesis due to their advantage of minimal material utilization and formation of less by-products. Trichloroisocyanuric acid (TCCA), a reagent with three reactive centers, was employed in the synthesis of spirooxindoles through the oxidative rearrangement of various N-protected tetrahydro-ß-carbolines. In this protocol, low equivalents of TCCA were required to access spirooxindoles (up to 99% yield) with a wide substrate scope. Furthermore, the applicability and robustness of this protocol were proven for the gram-scale total synthesis of natural alkaloids such as (±)-coerulescine (1) and (±)-horsfiline (2) in excellent yields.

Author Correction: Detection of SARS-CoV-2 in nasal swabs using MALDI-MS.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Detection of SARS-CoV-2 in nasal swabs using MALDI-MS.

Detection of SARS-CoV-2 using RT-PCR and other advanced methods can achieve high accuracy. However, their application is limited in countries that lack sufficient resources to handle large-scale testing during the COVID-19 pandemic. Here, we describe a method to detect SARS-CoV-2 in nasal swabs using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and machine learning analysis. This approach uses equipment and expertise commonly found in clinical laboratories in developing countries. We obtained mass spectra from a total of 362 samples (211 SARS-CoV-2-positive and 151 negative by RT-PCR) without prior sample preparation from three different laboratories. We tested two feature selection methods and six machine learning approaches to identify the top performing analysis approaches and determine the accuracy of SARS-CoV-2 detection. The support vector machine model provided the highest accuracy (93.9%), with 7% false positives and 5% false negatives. Our results suggest that MALDI-MS and machine learning analysis can be used to reliably detect SARS-CoV-2 in nasal swab samples.

Novel lipophilic analogues from 2,4-D and Propanil herbicides: Biological activity and kinetic studies.

This work describes the synthesis of new lipophilic amides and esters analogues of classical organochlorides herbicides by incorporation of long-chains from fatty acids and derivatives. The new fatty esters and amides were synthesized in 96-99% and 80-89% yields, respectively. In general, all compounds tested showed superior in vitro activity than commercial herbicides against growth L. sativa and A. cepa, in ranges 86-100% of germinative inhibition. The target compounds showed, significantly more susceptible towards acid hydrolysis than 2,4-dichlorophenoxyacetic acid (2,4-D). The kinetic and NMR studies showed that the incorporation of lipophilic chains resulted in a decrease in half-life time of new herbicides compounds (1.5 h) than 2,4-D (3 h). These findings suggest the synthesis of new lipophilic herbicides as potential alternative to traditional formulations, by incorporation of long fatty alkyl chains in the molecular structure of 2,4-D, resulting in superior in vitro herbicidal activity, best degradation behavior and more hydrophobic derivatives.

Bifunctional thiosquaramide catalyzed asymmetric reduction of dihydro-ß-carbolines and enantioselective synthesis of (-)-coerulescine and (-)-horsfiline by oxidative rearrangement.

Tetrahydro-ß-carboline (THBC) is a tricyclic ring system that can be found in a large number of bioactive alkaloids. Herein, we report a simple and efficient method for the synthesis of enantiopure THBCs through a chiral thiosquaramide (11b) catalyzed imine reduction of dihydro-ß-carbolines (17a-f). The in situ generated Pd-H employed as hydride source in the reaction of differently substituted chiral THBCs (18a-f) afforded high selectivities (R isomers, up to 96% ee) and good isolated yields (up to 88%). Moreover, the chiral thiosquaramide used also afforded exceptional catalyst activity in the syntheses of (-)-coerulescine (5) and (-)-horsfiline (6) with excellent enantioselectivities up to 98% and 93% ee, respectively, via an enantioselective oxidative rearrangement approach.

Gratidão no contexto brasileiro: mensuração e relações com personalidade e bem-estar / Gratitude in the Brazilian context: measurement and relationship with personality and well-being / Gratitud en el contexto brasileño: medición y relación con la personalidad y el bienestar

Pesquisas sobre gratidão têm se mostrado cada vez mais frequentes, sobretudo, devido às suas relações com o bem-estar. O objetivo desta pesquisa foi adaptar e buscar evidências de validade para o Brasil de uma medida de gratidão, o Gratitude Questionnaire. Foram realizados procedimentos controlados de tradução e aplicou-se o instrumento em 916 adultos, média de idade de 37 anos, predominantemente com ensino superior completo. Os resultados revelaram adequação dos dados à estrutura de um fator do instrumento, com adequada consistência interna e itens altamente discriminativos. As correlações entre gratidão e demais variáveis mostraram-se de acordo com o esperado teoricamente: positivas com autoestima, otimismo, satisfação de vida e afeto positivo. A gratidão ainda explicou o bem-estar subjetivo para além dos fatores de personalidade. O instrumento mostrou satisfatórias evidências de validade no contexto brasileiro, contudo, observou-se que ele carece de itens que cubram o espectro mais alto do traço latente. (AU)

Studies on gratitude are becoming increasingly frequent, mainly because of its relationship with well-being. The aim of this study was to adapt an instrument of gratitude, the Gratitude Questionnaire, and to seek evidence of its validity for Brazil. Controlled translation procedures were performed, and the instrument was applied to 916 adults, mean age 37 years, predominantly with higher education level. The results revealed adequacy of the data for a single factor structure of the instrument, with satisfactory reliability, and highly discriminative items. The correlations between gratitude and other variables were as theoretically expected: Positive with self-esteem, optimism, life satisfaction, and positive affect. Gratitude also explained subjective well-being beyond personality factors. The instrument showed satisfactory evidence of validity in the Brazilian context; however, it was observed that it lacks items that cover the higher spectrum of the latent trait. (AU)

Las investigaciones sobre la gratitud han sido cada vez más comunes, especialmente debido a sus relaciones con el bienestar. El objetivo de esta investigación fue adaptar y buscar evidencias de validez de un instrumento de gratitud, el Gratitude Questionnaire, para ser utilizado en Brasil. Se realizaron procedimientos de traducción controlados y se aplicó el instrumento a 916 adultos, con una edad media de 37 años, predominantemente con un nivel de educación superior. Los resultados revelaron la adecuación de los datos a la estructura de un factor del instrumento, con confiabilidad satisfactoria e ítems altamente discriminantes. Las correlaciones entre la gratitud y las demás variables fueron las esperadas: positivas con autoestima, optimismo, satisfacción con la vida, y afecto positivo. La gratitud también explica el bienestar subjetivo más allá de los factores de personalidad. El instrumento presentó satisfactoria evidencia de validez en el contexto brasileño; sin embargo, se observó que carece de elementos que cubran el espectro más alto del rasgo latente. (AU)

Substitution effects of NaCl by KCl and CaCl2 on Lipolysis of Salted Meat.

The objective of this study was to investigate the reduction and partial substitution effects of sodium chloride (NaCl) by potassium chloride (KCl) and calcium chloride (CaCl2) on lipolysis and lipid oxidation in salted meat aiming at reducing sodium content. To evaluate the effect of different salts on lipid oxidation thiobarbituric acid-reactive substances (TBARs) assay was performed along 180 days. Furthermore, ESI-MS/MS and GC analysis were conducted to detect and identify oxidized lipids, volatile compounds and free fatty acids profiles during the meat processing time. Lipid profiles from different salted meat demonstrated that CaCl2 salt have inducted more lipid oxidation when compared to the combination of NaCl and KCl salts, highlighting the implication of CaCl2 on increased lipolysis reactions. Moreover, the obtained results from both the analyses suggest that a combination of NaCl and KCl salts can be a good alternative for reducing the sodium content without compromising the quality of the salted meat.

Preparation of Hydrogel/Silver Nanohybrids Mediated by Tunable-Size Silver Nanoparticles for Potential Antibacterial Applications.

In this study, a versatile synthesis of silver nanoparticles of well-defined size by using hydrogels as a template and stabilizer of nanoparticle size is reported. The prepared hydrogels are based on polyvinyl alcohol and maleic acid as crosslinker agents. Three hydrogels with the same nature were synthesized, however, the crosslinking degree was varied. The silver nanoparticles were synthesized into each prepared hydrogel matrix achieving three significant, different-sized nanoparticles that were spherical in shape with a narrow size distribution. It is likely that the polymer network stabilized the nanoparticles. It was determined that the hydrogel network structure can control the size and shape of the nanoparticles. The hydrogel/silver nanohybrids were characterized by swelling degree, Thermal Gravimetric Analysis (TGA), Fourier Transform Infrared (FT-IR), Scanning Electron Microscopy (SEM) and Transmission Electron Microscope (TEM). Antibacterial activity against Staphylococcus aureus was evaluated, confirming antimicrobial action of the encapsulated silver nanoparticles into the hydrogels.

Ru(II)-Catalyzed Regioselective Hydroxymethylation of ß-Carbolines and Isoquinolines via C-H Functionalization: Probing the Mechanism by Online ESI-MS/MS Screening.

A Ru(II)-catalyzed regioselective C-H activation toward hydroxymethylation of ß-carbolines and isoquinolines as effective directing groups has been developed, and the mechanism was probed by using online electrospray ionization-tandem mass spectrometry. The introduction of the hydroxymethyl group in the biologically relevant molecules routed via C-H functionalization remains an important task. Gratifyingly, this protocol draws attention to the regioselective formation of monohydroxymethylated ß-carboline/isoquinoline products exclusively.

MALDI coupled to modified traveling wave ion mobility mass spectrometry for fast enantiomeric determination.

In this work, the use of MALDI traveling wave ion mobility spectrometry-mass spectrometry (MALDI-TWIMS-MS) for stereoselective structural analysis of direct cleavage and identification of 2-substituted piperidines obtained through solid-phase asymmetric synthesis by using heterogeneous 8-phenylmenthyl-based chiral auxiliary resins. A strategy for gas-phase chiral and structural characterization of small molecular weight molecules by using MALDI-IMS-MS technique is discussed. Because both MALDI and IMS do not directly offer chiral resolution, an easy methodology by adding a chiral phase is described to carry out in situ online ion/molecule complexation with different chiral analytes inside the mass spectrometer. Piperidine enantiomers were resolved, and separation obtained shows dependence of surface areas. To corroborate this assumption and elucidate the separation mechanism to accomplish an analytical technique by which fast determination of the chirality of molecules may be determined for a wide range organic compound applications, it was performed DFT calculations to determine the cross-sectional areas of proton-bound dimer complexes. Drift times are affected by cross-sectional areas, correlating bigger times with bigger molecular volumes during the ion mobility experiments of proton-bound dimer complexes.

Rational Development of a Novel Hydrogel as a pH-Sensitive Controlled Release System for Nifedipine.

This work depicts the rational development (in-silico design, synthesis, characterization and in-vitro evaluation) of polyvinyl alcohol hydrogels (PVAH) cross-linked with maleic acid (MA) and linked to γ-cyclodextrin molecules (γ-CDPVAHMA) as systems for the controlled and sustained release of nifedipine (NFD). Through computational studies, the structural blocks (PVA chain + dicarboxylic acid + γ-CD) of 20 different hydrogels were evaluated to test their interaction energies (ΔE) with NFD. According to the ΔE obtained, the hydrogel cross-linked with maleic acid was selected. To characterize the intermolecular interactions between NFD and γ-CDPVAHMA, molecular dynamics simulation studies were carried out. Experimentally, three hydrogel formulations with different proportions of γ-CD (2.43%, 3.61% and 4.76%) were synthesized and characterized. Both loading and release of NFD from the hydrogels were evaluated at acid and basic pH. The computational and experimental results show that γ-CDs linked to the hydrogels were able to form 1:1 inclusion complexes with NFD molecules. Finally, γ-CDPVAHMA-3 demonstrated to be the best pH-sensitive release platform for nifedipine. Its effectiveness could significantly reduce the adverse effects caused by the anticipated release of NFD in the stomach of patients.

Selective and Efficient Arsenic Recovery from Water through Quaternary Amino-Functionalized Silica.

The free-radical graft polymerization of acryloxyethyl-trimethylammonium chloride onto commercial silica particles was studied experimentally for extraction of arsenic ions from water. Two steps were used to graft acryloxyethyl-trimethylammonium chloride (Q) onto the surface of nanosilica: anchoring vinyltrimethoxysilane (VTMSO) onto the surface of silica to modify it with double bonds and then grafting Q onto the surface of silica with potassium persulfate as an initiator. The products were characterized by Fourier-transform infrared (FT-IR), the thermogravimetric analysis (TGA), scanning electron microscopy (SEM), 13C, 29Si nuclear magnetic resonance (NMR), and X-ray powder diffraction (XRD). The results showed that it is easy to graft Q onto the surface of silica under radical polimerization. The morphology analysis of silica and modified silica indicated that the silica decreased the size scale after modification. Q/VTMSO-SiO2 was tested for its ability to remove arsenic from drinking water. The results show that the new silica hybrid particles efficiently remove all arsenate ions. In addition, Q/VTMSO-SiO2 showed better sorption capacities for other metal ions (such as copper, zinc, chromium, uranium, vanadium, and lead) than a commercial water filter.

Rosé Wine Fining Using Polyvinylpolypyrrolidone: Colorimetry, Targeted Polyphenomics, and Molecular Dynamics Simulations.

Polyvinylpolypyrrolidone (PVPP) is a fining agent polymer used in winemaking to adjust rosé wine color and to prevent organoleptic degradations by reducing polyphenol content. The impact of this polymer on color parameters and polyphenols of rosé wines was investigated, and the binding specificity of polyphenols toward PVPP was determined. Color measured by colorimetry decreased after treatment, thus confirming the adsorption of anthocyanins and other pigments. Phenolic composition was determined before and after fining by targeted polyphenomics (Ultra Performance Liquid Chromatography (UPLC)-Electrospray Ionization(ESI)-Mass Spectrometry (MS/MS)). MS analysis showed adsorption differences among polyphenol families. Flavonols (42%) and flavanols (64%) were the most affected. Anthocyanins were not strongly adsorbed on average (12%), but a specific adsorption of coumaroylated anthocyanins was observed (37%). Intermolecular interactions were also studied using molecular dynamics simulations. Relative adsorptions of flavanols were correlated with the calculated interaction energies. The specific affinity of coumaroylated anthocyanins toward PVPP was also well explained by the molecular modeling.

Fast detection of Listeria monocytogenes through a nanohybrid quantum dot complex.

Listeria monocytogenes is a recognized foodborne pathogen that causes listeriosis in susceptible consumers. Currently, the detection systems for Listeria in food detect live and dead bacteria, being the viable microorganisms most relevant for their ability to cause sickness in the population at risk. For this reason, a new nanohybrid compound was developed for the optical detection of Listeria that was based on polyamidoamine dendrimers functionalized with an auxotrophic cofactor (lipoic acid), together with the coupling of fluorescent semiconductor crystals (quantum dots). The nanohybrid sensor has a detection limit for viable L. monocytogenes of 5.19 × 103 colony-forming units per milliliter under epifluorescence microscopy. It was specific when used among other pathogens commonly found in food.