Allenyl‐β‐lactams: versatile scaffolds for the synthesis of heterocycles

The hybrid allenic β‐lactam moiety represents an excellent building block for carbo‐ and heterocyclization reactions, affording a large number of cyclic structures containing different sized skeletons in a single step. This strategy has been studied under thermal and radical‐induced conditions. More recently, the use of transition‐metal catalysis has been introduced as an alternative that relies on the activation of the allenic component. On the other hand, the intramolecular version has attracted much attention as a strategy for the synthesis of bi‐ and tricyclic compounds in a regio‐ and stereoselective manner. This overview focuses on the most recently developed cyclizations on 2‐azetidinone‐tethered allenes along with remarkable early works accounting for the mechanism, as well as for the regio‐ and diastereoselectivities of the cyclizations. DOI 10.1002/tcr.201100011     

Simultaneous determination of a selected group of cytostatic drugs in water using high-performance liquid chromatography-triple-quadrupole mass spectrometry

In recent years, an increasing concern has risen about the presence of pharmaceuticals in the aquatic environment. Despite their toxicity, increasing consumption and release into the municipal sewage, only a few studies have been focused on cytostatic drugs, mainly due to the lack of methods for their simultaneous analysis. In this work, a method, based on solid-phase extraction prior to high-performance liquid chromatography-triple quadrupole mass spectrometry determination, was optimized and validated for the simultaneous determination of some (14) of the most widely used cytostatic drugs in river water, influent and effluent wastewater. Process efficiency was in the range between 41 and 99% in real samples, except for cytarabine (24%), docetaxel (17%) and methotrexate (30%), due to suppression effects; precision values were <11%, except for gemcitabine (up to 19%); and detection limits were in the range between 0.1 and 38 ng/L. Cytarabine, doxorubicin, etoposide, gemcitabine, iphosphamide and vinorelbine were found at concentration levels up to 14 ng/L in influent and effluent wastewater, showing an insignificant decrease during sewage treatment; cytarabine and gemcitabine were found in effluent wastewater and were also detected in river water associated with effluent discharges.     

Hybrid nanoparticle design based on cationized gelatin and the polyanions dextran sulfate and chondroitin sulfate for ocular gene therapy

We describe the development of hybrid nanoparticles composed of cationized gelatin and the polyanions CS and DS for gene therapy in the ocular surface. The physicochemical properties of the nanoparticles that impact their bioperformance, such as average size and zeta potential, can be conveniently modulated by changing the ratio of polymers and the crosslinker. These systems associate plasmid DNA and are able to protect it from DNase I degradation. We corroborate that the introduction of CS or DS in the formulation decreases the in vitro toxicity of the nanoparticles to human corneal cells without compromising the transfection efficiency. These nanoparticles are potential candidates for the development of safer and more effective nanomedicines for ocular therapy.     

Laser microperforated biodegradable microbial polyhydroxyalkanoate substrates for tissue repair strategies: an infrared microspectroscopy study

Flexible and biodegradable film substrates prepared by solvent casting from poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBHV) solutions in chloroform were microperforated by ultraviolet laser ablation and subsequently characterized using infrared (IR) microspectroscopy and imaging techniques and scanning electron microscopy (SEM). Both transmission synchrotron IR microspectroscopy and attenuated total reflectance microspectroscopy measurements demonstrate variations in the polymer at the ablated pore rims, including evidence for changes in chemical structure and crystallinity. SEM results on microperforated PHBHV substrates after cell culture demonstrated that the physical and chemical changes observed in the biomaterial did not hinder cell migration through the pores.     

Free Ca<Superscript>2+</Superscript> as an early intracellular biomarker of exposure of cyanobacteria to environmental pollution

Calcium functions as a versatile messenger in a wide variety of eukaryotic and prokaryotic cells. Cyanobacteria are photoautotrophs which have a great ecological impact as primary producers. Our research group has presented solid evidence of a role of calcium in the perception of environmental changes by cyanobacteria and their acclimation to these changes. We constructed a recombinant strain of the freshwater cyanobacterium Anabaena sp. PCC 7120 that constitutively expresses the calcium-binding photoprotein apoaequorin, enabling in-vivo monitoring of any fluctuation in the intracellular free calcium concentration of the cyanobacterium in response to any environmental stimulus. The “Ca²⁺ signature” is the combination of changes in all Ca²⁺ signal properties (magnitude, duration, frequency, source of the signal) produced by a specific stimulus. We recorded and analyzed the Ca²⁺ signatures generated by exposure of the cyanobacterium to different groups of environmental pollutants, for example cations, anions, organic solvents, naphthalene, and pharmaceuticals. We found that, in general, each group of tested chemicals triggered a specific calcium signature in a reproducible and dose-dependent manner. We hypothesize that these Ca²⁺ signals may be related to the cellular mechanisms of pollutant perception and ultimately to their toxic mode of action. We recorded Ca²⁺ signals triggered by binary mixtures of pollutants and a signal induced by a real wastewater sample which could be mimicked by mixing its main constituents. Because Ca²⁺ signatures were induced before toxicity was evident, we propose that intracellular free Ca²⁺ may serve as an early biomarker of exposure to environmental pollution.     

Analysis of staphylococcal enterotoxin A in milk by matrix-assisted laser desorption/ionization-time of flight mass spectrometry

Staphylococcal enterotoxin A (SEA) is an exotoxin excreted mainly by Staphylococcus aureus and nowadays is the most prevalent compound in staphylococcal food poisoning worldwide. SEA is highly heat-resistant, and usual cooking times and temperatures are unlikely to completely inactivate it. A procedure for extraction of this toxin based on protein precipitation with a mixture of dichloromethane and acidified water was used before SDS-PAGE separation of soluble proteins. Finally, bands of interest were excised from the gel and in-gel enzymatic digestion was done. SEA from pasteurized milk was detected with matrix-assisted laser-desorption/ionization-time of flight (MALDI-TOF) mass spectrometry. Nineteen peptides (range 800-2400 Da) were identified as products of trypsin cleavage of the SEA standard with a score of 204 and 73% coverage of the protein sequence, whereas thirteen peptides were revealed for SEA extracted from milk with a score of 148 and 58% sequence coverage obtained. This procedure has been applied successfully for identification of SEA in milk.     

A zebrafish scale assay to monitor dioxin-like activity in surface water samples

New regulations on water quality require a close control of the possible biological activities known or unexpected pollutants may bring about. We present here a protocol based on the direct exposure of zebrafish to river water and the analysis of expression of specific genes in their scales to determine the presence of compounds with dioxin-like biological activity. The method does not require the killing of animals and allows detection of the biological activity after a single day of exposure. When tested, the method with real samples from the Llobregat River, clear temporal and spatial variations were observed, demonstrating its suitability for monitoring natural variations in water quality linked to specific discharges. High biological activities were unrelated to the currently checked water quality parameters (macropollutants, turbidity, TOC, etc.), but they did correlate with the presence of micropollutants (estrogens, detergents, etc.) related to domestic and/or industrial runoffs. The scale assay therefore provides a new tool to evaluate water quality changes that cannot be easily derived from the existing standard analytical procedures. It ranks among the very few described protocols able to detect biological effects from natural water samples, without a pre-concentration step, and after only 24 h of exposure.     

Nanoscopic optical sensors based on functional supramolecular hybrid materials

This review highlights how the combination of supramolecular principles and nanoscopic solid structures enables the design of new hybrid sensing ensembles with improved sensitivity and/or selectivity and for the targeting of analytes for which selectivity is hard to achieve by conventional methods. Such ideas are bridging the gap between molecules, materials sciences and nanotechnology. Relevant examples will be detailed, taking into account functional aspects such as (1) enhanced coordination of functionalized solids, (2) enhanced signalling through preorganization, (3) signalling by assembly–disassembly of nanoscopic objects, (4) biomimetic probes utilizing discrimination by polarity and size and (5) distinct switching and gating protocols. These strategies are opening new prospects for sensor research and signalling paradigms at the frontier between nanotechnology, smart materials and supramolecular chemistry.     

Quasi-filiform Leibniz algebras of maximum length

The n-dimensional p-filiform Leibniz algebras of maximum length have already been studied with 0 ≤ p ≤ 2. For Lie algebras whose nilindex is equal to n−2 there is only one characteristic sequence, (n − 2, 1, 1), while in Leibniz theory we obtain the two possibilities: (n − 2, 1, 1) and (n − 2, 2). The first case (the 2-filiform case) is already known. The present paper deals with the second case, i.e., quasi-filiform non-Lie-Leibniz algebras of maximum length. Therefore this work completes the study of the maximum length of the Leibniz algebras with nilindex n − p with 0 ≤ p ≤ 2.     

Polynomial approximation of nonlinear differential systems with prefixed accuracy

This paper presents a method for constructing polynomial approximations of the solutions of nonlinear initial value systems of differential equations. Given an a priori chosen accuracy, the degree of the vector polynomial can be adapted so that the approximate solution has the required precision. The method is based on the AI-method of Dzyadyk developed for the scalar case, and the computational cost is shown to be competitive with other methods.