Nonaqueous capillary electrophoresis in coated capillaries: an interesting alternative for proteomic applications

This work brings together some contributions for the use of nonaqueous media for proteomic analysis, for both capillary electrophoresis (CE) separation and the preparation of tryptic digests. First, a ternary nonaqueous buffer consisting of 60/30/10 v/v methanol/acetonitrile/acetic acid with 12.5 mmol/L ammonium acetate was optimized for CE separation of the tryptic digest of lysozyme. Lysozyme was chosen as a model system for the protein digestion, which has also been prepared in an organic-rich medium with methanol/50 mmol/L NH(4)HCO(3), pH 8.0 (60/40 v/v). The separation results were compared to in silico (PeptideCutter program) digestion conditions, and high-efficiency peak separation (18 peaks) was obtained in 20 min with an electric field of 350 V/cm. In addition, we have evaluated the stability of a coated capillary with poly-N,N-dimethylacrylamide (60/30 cm total/effective length and 75 microm ID) for over 100 runs of tryptic digest with the nonaqueous background electrolyte solvent system. The migration times for ten selected peptide peaks presented 3-7% relative standard deviation.     

Phase-selective alternating current polarographic assay of methotrexate in human serum

The a.c. polarographic behaviour of methotrexate (MTX) was studied and the nature of the process taking place at the dropping mercury electrode was elucidated. Both the molecule and its reduced product appeared to be absorbed at the surface of the electrode. The observed electrochemical behaviour was in close agreement with theoretical predictions for an absorbed species which is reversibly reduced. This permitted a very sensitive and selective determination of MTX in serum samples by phase-selective a.c. polarography. The method, which involves a very simple and rapid previous clean-up procedure, has a limit of detection of 3.0 × 10^?7 M in serum and the results compare well with those obtained by liquid chromatography with oxidative amperometric detection (LC-ED) at +1.1 V. Both methods form an interesting alternative to others previously reported for monitoring MTX in cancer patients under treatment with high doses of the drug.     

Sustainable synthetic methods: domino construction of dihydropyridin-4-ones and beta-amino esters in aqueous ethanol

Domino reactions were designed to allow the byproduct of an upstream reaction to be internally recycled to catalyze a downstream reaction in a one-pot tandem sequence. Nitroarene reduction by In(0) generates an amine and In (III) byproducts. Addition of aldehyde followed by Danishefsky's diene or silyl ketene acetal provides access to dihydropyridin-4-ones or beta-amino esters, respectively, in yields that are comparable or superior to the reported stepwise reactions.     

Monitoring Stimulated Darkening from UV-C Light on Different Bean Genotypes by NMR Spectroscopy

The use of UV-C cool white light on bean (Phaseolus vulgaris L.) seeds significantly increases the biochemical seed coat post-harvest darkening process, whilst preserving seed germination. The aim of this work consists in monitoring the effect caused by the incidence of UV-C light on different bean genotypes using NMR spectroscopy. The genotype samples named IAC Alvorada; TAA Dama; BRS Estilo and BRS Pérola from the Agronomic Institute (IAC; Campinas; SP; Brazil) were evaluated. The following two methodologies were used: a prolonged darkening, in which the grain is placed in a room at a controlled temperature (298 K) and humidity for 90 days, simulating the supermarket shelf; an accelerated darkening, where the grains are exposed to UV-C light (254 nm) for 96 h. The experiments were performed using the following innovative time-domain (TD) NMR approaches: the RK-ROSE pulse sequence; one- and two-dimensional high resolution (HR) NMR experiments (¹H; ¹H-¹H COSY and ¹H-¹³C HSQC); chemometrics tools, such as PLS-DA and heat plots. The results suggest that the observed darkening occurs on the tegument after prolonged (90 days) and accelerated (96 h) conditions. In addition, the results indicate that phenylalanine is the relevant metabolite within this context, being able to participate in the chemical reactions accounted for by the darkening processes. Additionally, it is possible to confirm that a UV-C lamp accelerates oxidative enzymatic reactions and that the NMR methods used were a trustworthy approach to monitor and understand the darkening in bean seeds at metabolite level.     

Structure-Based Bioisosterism Design,Synthesis, Biological Evaluation and In Silico Studies of Benzamide Analogs as Potential Anthelmintics

A recent screen of 67,012 compounds identified a new family of compounds with excellent nematicidal activity: the ortho-substituted benzamide families Wact-11 and Wact-12. These compounds are active against Caenorhabditis elegans and parasitic nematodes by selectively inhibiting nematode complex II, and they display low toxicity in mammalian cells and vertebrate organisms. Although a big number of benzamides were tested against C. elegans in high-throughput screens, bioisosteres of the amide moiety were not represented in the chemical space examined. We thus identified an opportunity for the design, synthesis and evaluation of novel compounds, using bioisosteric replacements of the amide group present in benzamides. The compound Wact-11 was used as the reference scaffold to prepare a set of bioisosteres to be evaluated against C. elegans. Eight types of amide replacement were selected, including ester, thioamide, selenoamide, sulfonamide, alkyl thio- and oxo-amides, urea and triazole. The results allowed us to perform a structure–activity relationship, highlighting the relevance of the amide group for nematicide activity. Experimental evidence was complemented with in silico structural studies over a C. elegans complex II model as a molecular target of benzamides. Importantly, compound Wact-11 was active against the flatworm Echinococcus granulosus, suggesting a previously unreported pan-anthelmintic potential for benzamides.     

Quantitative structure activity relationships of 5-nitrofuran derivatives

Summary Quantitative structure-activity relationships were performed on a set of 5-nitrofuran derivatives. The correlation parameters used were hydrophobicity and connectivity. The former was measured by means of the capacity factor (log k _o ) obtained by HPLC and the latter through the molecular valence connectivity index^{1 v} obtained by computational methods. The biological activity data considered were growth inhibition percentages ofT. cruzi (GI % (48 h)) and half-maximal inhibitory concentration of Glutathione Reductase (I_{0.5 (max)}). Good adjustment, r=0.98, was obtained if a logarithmic model is used for I_{0.5 (max)} correlations. When GI% is considered, correlations were poorer and the consideration of both structural parameters was necessary for their improvement, r=0.94.     

Analyzing and modeling real-world phenomena with complex networks: a survey of applications

The success of new scientific areas can be assessed by their potential in contributing to new theoretical approaches and in applications to real-world problems. Complex networks have fared extremely well in both of these aspects, with their sound theoretical basis being developed over the years and with a variety of applications. In this survey, we analyze the applications of complex networks to real-world problems and data, with emphasis in representation, analysis and modeling. A diversity of phenomena are surveyed, which may be classified into no less than 11 areas, providing a clear indication of the impact of the field of complex networks.