Evaluation of flavonols and derivatives as human cathepsin B inhibitor

Cathepsin B (catB) is a cysteine protease involved in tumour progression and represents a potential therapeutic target in cancer. Among the 15 evaluated extracts from cerrado biome, Myrcia lingua Berg. (Myrtaceae) extract demonstrated to be a source of compounds with potential to inhibit catB. Using bioactivity-guided fractionation, we have found flavonols as inhibitors and also some other derivatives were obtained. From the evaluated compounds, myricetin (5) and quercetin (6) showed the most promising results with IC₅₀ of 4.9 and 8.2 μM, respectively, and mode of inhibition as uncompetitive on catB. The results demonstrated polyhydroxylated flavonols as promising inhibitors of catB.     

pH-sensitive nanostructured architectures based on synthetic and/or natural weak polyelectrolytes

This study aims to evidence the influence of polyelectrolytes structure and the number of double layers on the properties of some new nanostructured architectures formed by layer-by-layer self-assembly of complementary weak polyelectrolytes on planar surfaces. For this purpose, we used chitosan and poly(allylamine hydrochloride) as polycations, and poly(acrylic acid) and poly(2-acrylamido-2-methylpropanesulfonic acid–co-acrylic acid) as polyanions. To get a direct image on the polyelectrolyte multilayers formation and properties, gravimetry, infrared spectroscopy, and atomic force microscopy have been used. The capacity of the polyions to overcompensate the complementary polyions charges, and thus to influence the swelling degree in water of thin films, was strongly influenced by the chain structure and flexibility. A special attention was paid to the responsiveness of the new composite materials to the pH of the swelling environment.     

New palladium(II) complexes with pyrazole ligands

This study describes the synthesis, IR, ¹H, and ¹³C{¹H} NMR spectroscopic as well the thermal characterization of the new palladium(II) pyrazolyl complexes [PdCl₂(HmPz)₂] 1, [PdBr₂(HmPz)₂] 2, [PdI₂(HmPz)₂] 3, [Pd(SCN)₂(HmPz)₂] 4 {HmPz = 4-methylpyrazole}. The residues of the thermal decomposition were identified as Pd⁰ by X-ray powder diffraction. From the initial decomposition temperatures, the thermal stability of the complexes can be ordered in the sequence: 1 > 2 > 4 ≈ 3. The cytotoxic activities of the complexes and the ligand were investigated against two murine cancer cell lines: mammary adenocarcinoma (LM3) and lung adenocarcinoma (LP07) and compared to cisplatin under the same experimental conditions.     

Multi-syringe flow-injection systems improve antioxidant assessment

Conventionally, measuring antioxidant capacity is time consuming, laborious and costly, especially in routine work. These limitations can be overcome using multi-syringe flow-injection analysis (MSFIA), which has succeeded in automating the most widely applied antioxidant-capacity assays that use chromogen radicals or reactive species found in vivo. We highlight the features of MSFIA and improved methodologies in using MSFIA to measure antioxidant capacity.     

Effect of PNA backbone modifications on cyanine dye binding to PNA-DNA duplexes investigated by optical spectroscopy and molecular dynamics simulations

Optical spectroscopy and molecular dynamics simulations have been used to study the interaction between a cationic cyanine dye and peptide nucleic acid (PNA)-DNA duplexes. This recognition event is important because it leads to a visible color change, signaling successful hybridization of PNA with a complementary DNA strand. We previously proposed that the dye recognized the minor groove of the duplex, using it as a template for the assembly of a helical aggregate. Consistent with this, we now report that addition of isobutyl groups to the PNA backbone hinders aggregation of the dye when the substituents project into the minor groove but have a weaker effect if directed out of the groove. UV-Visible and circular dichroic spectroscopy were used to compare aggregation on the different PNA-DNA duplexes, while molecular dynamics simulations were used to confirm that the substituents block the minor groove to varying degrees, depending on the configuration of the starting amino acid. In addition to a simple steric blockage effect of the substituent, the simulations suggest that directing the isobutyl group into the minor groove causes the groove to narrow and the duplex to become more rigid, structural perturbations that are relevant to the growing interest in backbone-modified PNA for applications in the biological and materials sciences.     

Multi-Syringe Flow Injection System with In-Line Pre-Concentration for the Determination of Total Phenolic Compounds

A multi-syringe flow injection system for the determination of total phenolics based on the 4-aminoantipyrine reaction is proposed. In-line preconcentration using solid-phase extraction was implemented, offering an environmentally friendly alternative to organic solvent extraction performed in the batch procedure and in previously described flow methodologies. Therefore, phenolic compounds were retained in Amberlite XAD4 resin using acidic conditions. The elution was carried out using 0.10molL^–1 NaOH solution, promoting the ionisation of the retained phenolic compounds, and thus their desorption.Since different elution profiles were obtained for several phenol derivatives, the calibration curves were established using the peak area as analytical signal. Moreover, a dynamic calibration range was applied by using a variable sample volume (0.500–6.00mL) and calibration curves based on the mass of phenol retained in the pre-concentration column. A methodology based on a fixed sample volume (24.0mL) was also proposed for determination at concentration levels below 50µgL^–1. A limit of detection of 52ng of phenol (9 or 2µgL^–1) was achieved with a sampling frequency of 10–16h^–1 for the variable volume method and 4h^–1 for the fixed volume method. The application of the proposed methodology to reference material provided results that were within the certified acceptance limits.     

Total synthesis of (S)-(+)-imperanene. Effective use of regio- and enantioselective intramolecular carbon-hydrogen insertion reactions catalyzed by chiral dirhodium(II) carboxamidates

The total synthesis of (S)-(+)-imperanene, a natural product found in Chinese medicine, has been completed in 12 steps from a commercially available cinnamic acid. The key step is highly enantioselective carbon-hydrogen insertion from a diazoacetate using a chiral dirhodium(II) carboxamidate catalyst. An elimination process essential to the construction has been optimized to avoid intramolecular Friedel-Crafts alkylation.     

Determination of aluminum by electrothermal atomic absorption spectroscopy in lubricating oils emulsified in a sequential injection analysis system

The sequential injection (SIA) technique was applied for the on-line preparation of an “oil in water” microemulsion and for the determination of aluminum in new and used lubricating oils by electrothermal atomic absorption spectrometry (ET AAS) with Zeeman-effect background correction. Respectively, 1.0, 0.5 and 1.0 ml of surfactants mixture, sample and co-surfactant (sec-butanol) solutions were sequentially aspirated to a holding coil. The sonication and repetitive change of the flowing direction improved the stability of the different emulsion types (oil in water, water in oil and microemulsion). The emulsified zone was pumped to fill the sampling arm of the spectrometer with a sub-sample of 200 μl. Then, 10 μl of this sample solution were introduced by means of air displacement in the graphite tube atomizer. This sequence was timed to synchronize with the previous introduction of 15 μg of Mg(NO₃)₂ (in a 10 μl) by the spectrometer autosampler. The entire SIA system was controlled by a computer, independent of the spectrometer. The furnace program was carried out by employing a heating cycle in four steps: drying (two steps at 110 and 130 °C), pyrolisis (at 1500 °C), atomization (at 2400 °C) and cleaning (at 2400 °C). The calibration graph was linear from 7.7 to 120 μg Al l⁻¹. The characteristic mass (mo) was 33.2 pg/0.0044 s and the detection limit was 2.3 μg Al l⁻¹. The relative standard (RSD) of the method, evaluated by replicate analyses of different lubricating oil samples varied in all cases between 1.5 and 1.7%, and the recovery values found in the analysis of spiked samples ranged from 97.2 to 100.4%. The agreement between the observed and reference values obtained from two NIST Standard Certified Materials was good. The method was simple and satisfactory for determining aluminum in new and used lubricating oils.     

On-line electrothermal atomic absorption spectrometry configurations: recent developments and trends

In the present mini-review, an account of the actual state-of-the-art and future possibilities offered by on-line ET-AAS is presented. Topics such as: (1) on-line analyte preconcentration (by means of precipitation, sorption, solvent extraction, and solid phase extraction); (2) analyte separation by means of chromatography, and electrochemical, microdialysis and chemical vapor generation processes; and (3) sample treatment (by microwave sample digestion, sample emulsification and dilution processes) are used to illustrate the versatility of flow injection, sequential injection analysis, stop flow and continuous flow, when coupled to a graphite furnace. The use of some of the on-line systems for speciation and the simultaneous determination of different analytes is underlined.     

CHEMIENERGIZED SPECIES IN PEROXIDASE SYSTEMS

Abstract— Several hemeprotein-catalyzed reactions generate products of the type expected from the cleavage of a high energy intermediate. For some systems, the formation, in high yield, of a carbonyl compound in its excited triplet state has been firmly established on the basis of (i) equivalence of the chemiluminescence and phosphorescence spectra of the expected products; (ii) energy transfer to sensitizers containing heavy atoms and (iii) occurrence of photoproducts. The excited species appears to be generated within the enzyme and shielded from quenching by oxygen. It may be quenched, however, via long-range triplet-singlet energy transfer.
This work strongly supports our hypothesis that excited electronic states are also formed in biological systems which are not necessarily bioluminescent. One of the functions which peroxidases may thus fulfill might be the utilization of the potential of photochemistry in the absence of light.