A General Approach to Substituted Benzimidazoles and Benzoxazoles via Heterogeneous Palladium‐Catalyzed Hydrogen‐Transfer with Primary Amines

The synthesis of benzimidazoles starting from o‐phenylenediamines and amines in the presence of palladium on charcoal as catalyst is reported. Under microwave dielectric heating it is possible to use a tertiary, a secondary, and even a primary amine as the substrate for a palladium‐mediated process to get 2‐substituted or 1,2‐disubstituted benzimidazoles, depending on the nature of the o‐phenylenediamine employed. Primary amines are the most suitable reagents for the atom economy of the overall process that resulted to be general as several different substituted benzimidazoles were obtained in good yield. Benzoxazoles can be also prepared starting from primary amines and o‐aminophenol. The reaction is also highly selective as no (poly)‐alkylated phenylenediamines or cross‐contaminated benzimidazoles are obtained starting from N‐monoalkylphenylenediamines. This behavior was interpreted as a scarce aptitude to dehydrogenation of the methylene bonded to the aromatic NH of N‐alkylarylamines. The experiments carried out consent to draw an almost complete picture of the reaction pathways occurring during the process. The catalyst can be recycled several times and, although far from optimal performances, catalyst TON=90 is encouraging for further large‐scale optimization protocols. In addition, the palladium on charcoal‐catalyzed microwave‐assisted reaction of o‐phenylenediamine gives de‐alkylation of tertiary amines and transformation into the secondary ones.     

Moving beyond PARP Inhibition: Current State and Future Perspectives in Breast Cancer

Breast cancer is the most frequent and lethal tumor in women and finding the best therapeutic strategy for each patient is an important challenge. PARP inhibitors (PARPis) are the first, clinically approved drugs designed to exploit synthetic lethality in tumors harboring BRCA1/2 mutations. Recent evidence indicates that PARPis have the potential to be used both in monotherapy and combination strategies in breast cancer treatment. In this review, we show the mechanism of action of PARPis and discuss the latest clinical applications in different breast cancer treatment settings, including the use as neoadjuvant and adjuvant approaches. Furthermore, as a class, PARPis show many similarities but also certain critical differences which can have essential clinical implications. Finally, we report the current knowledge about the resistance mechanisms to PARPis. A systematic PubMed search, using the entry terms “PARP inhibitors” and “breast cancer”, was performed to identify all published clinical trials (Phase I-II-III) and ongoing trials (ClinicalTrials.gov), that have been reported and discussed in this review.     

Novel Lytic Enzyme of Prophage Origin from Clostridium botulinum E3 Strain Alaska E43 with Bactericidal Activity against Clostridial Cells

Clostridium botulinum is a Gram-positive, anaerobic, spore-forming bacterium capable of producing botulinum toxin and responsible for botulism of humans and animals. Phage-encoded enzymes called endolysins, which can lyse bacteria when exposed externally, have potential as agents to combat bacteria of the genus Clostridium. Bioinformatics analysis revealed in the genomes of several Clostridium species genes encoding putative N-acetylmuramoyl-l-alanine amidases with anti-clostridial potential. One such enzyme, designated as LysB (224-aa), from the prophage of C. botulinum E3 strain Alaska E43 was chosen for further analysis. The recombinant 27,726 Da protein was expressed and purified from E. coli Tuner(DE3) with a yield of 37.5 mg per 1 L of cell culture. Size-exclusion chromatography and analytical ultracentrifugation experiments showed that the protein is dimeric in solution. Bioinformatics analysis and results of site-directed mutagenesis studies imply that five residues, namely H25, Y54, H126, S132, and C134, form the catalytic center of the enzyme. Twelve other residues, namely M13, H43, N47, G48, W49, A50, L73, A75, H76, Q78, N81, and Y182, were predicted to be involved in anchoring the protein to the lipoteichoic acid, a significant component of the Gram-positive bacterial cell wall. The LysB enzyme demonstrated lytic activity against bacteria belonging to the genera Clostridium, Bacillus, Staphylococcus, and Deinococcus, but did not lyse Gram-negative bacteria. Optimal lytic activity of LysB occurred between pH 4.0 and 7.5 in the absence of NaCl. This work presents the first characterization of an endolysin derived from a C. botulinum Group II prophage, which can potentially be used to control this important pathogen.     

Structural Aspects of the Behavior of Lead-Free Solder in the Corrosive Solution

In oxidizing environments, most tin-based lead (Pb)-free alloys form a tin oxide that is easily eroded or mechanically damaged, affecting corrosion resistance and thus reliability of the soldered joints. In this study, the effect of microstructure heterogeneity on corrosion behavior of Pb-free solder candidate systems has been investigated on the example of as-cast and heat-treated alloys. The research was focused on a comparison between the corrosion resistance of binary Sn-Zn and ternary Sn-Zn-Cu alloys. Accelerated corrosion tests were performed by means of electrochemical methods in the sodium sulfate solution (VI), Na₂SO₄, of about 0.5 M concentration, pH adjusted to 2 by means of concentrated H₂SO₄ acid. In these tests, the corrosion potentials as well as polarization curves were determined for the selected alloys in as-cast state and after their heat treatment using different combinations of processing parameters. The measurements of basic electrochemical characteristics were made, i.e., the corrosion current (i _corr μA/cm²) and Tafel coefficients, both cathodic (b _c V/dec) and anodic (b _a V/dec) ones. Detailed structural characterization of as-cast and heat-treated alloys before and after accelerated corrosion tests has been made under a wide range of magnifications using light microscopy and scanning electron microscopy observations. The results showed that structural heterogeneity of the examined alloys, attributed to the presence of secondary phases, and affected by their size and distribution, significantly influences the behavior of the examined Pb-free Sn-Zn-based alloys in the corrosive environment.     

Supercritical Fluid Chromatography × Ultra-High Pressure Liquid Chromatography for Red Chilli Pepper Fingerprinting by Photodiode Array,Quadrupole-Time-of-Flight and Ion Mobility Mass Spectrometry (SFC × RP-UHPLC-PDA-Q-ToF MS-IMS)

The coupling of normal phase and reversed phase liquid chromatography (NP-LC × RP-LC) is one of the most effective ways to increase orthogonality in two-dimensional comprehensive separations, being the two retention mechanisms truly independent. However, such coupling is not straightforward to implement, due to immiscibility of the mobile phases, poor peak focusing at the head of the secondary column (²D), signal interferences and peak deterioration. In this research, supercritical fluid chromatography (SFC) was used in the first dimension (¹D), coupled to ultra high pressure LC (UHPLC), to alleviate incompatibility issues and provide a number of advantages related to the use of supercritical CO₂. An on-line SFC × RP-UHPLC system was implemented in an automated fashion, around two 2-position, six-port switching valves equipped with octadecyl silica cartridges for effective trapping and focusing of the analytes eluted from ¹D. A water make-up flow added to the SFC effluent permitted to efficiently focus the solutes on the sorbent material and to reduce interferences of the expanded CO₂ on the ²D separation. In addition to photodiode array and quadrupole-time-of-flight mass spectrometry detection, ion mobility separation based on analyte mass, shape and size added a fourth separation dimension for carotenoid fingerprinting in a red chilli pepper sample.     

Electrochemically assisted methane production in a biofilm reactor

Microbial electrolysis is a new technology for the production of value-added products, such as gaseous biofuels, from waste organic substrates. This study describes the performance of a methane-producing microbial electrolysis cell (MEC) operated at ambient temperature with a Geobacter sulfurreducens microbial bioanode and a methanogenic microbial biocathode. The cell was initially operated at a controlled cathode potential of −850 mV (vs. standard hydrogen electrode, SHE) in order to develop a methanogenic biofilm capable of reducing carbon dioxide to methane gas using abiotically produced hydrogen gas or directly the polarized electrode as electron donors. Subsequently, G. sulfurreducens was inoculated at the anode and the MEC was operated at a controlled anode potential of +500 mV, with acetate serving as electron donor. The rate of methane production at the cathode was found to be primarily limited by the acetate oxidation kinetics and in turn by G. sulfurreducens concentration at the anode of the MEC. Temperature had also a main impact on acetate oxidation kinetics, with an apparent activation energy of 58.1 kJ mol⁻¹.     

On semidefinite programming bounds for graph bandwidth

In this paper, we propose two new lower bounds on graph bandwidth and cyclic bandwidth based on semidefinite programming (SDP) relaxations of the quadratic assignment problem. We compare the new bounds with two other SDP bounds reported in [A. Blum, G. Konjevod, R. Ravi, and S. Vempala, Semi-definite relaxations for minimum bandwidth and other vertex-ordering problems, Theoret. Comput. Sci. 235(1) (2000), pp. 25–42; J. Povh and F. Rendl, A copositive programming approach to graph partitioning, SIAM J. Optim. 18(1) (2007), pp. 223–241].     

Development and Experimental Testing of an Optical Micro-Spectroscopic Technique Incorporating True Line-Scan Excitation

Multiphoton micro-spectroscopy, employing diffraction optics and electron-multiplying CCD (EMCCD) cameras, is a suitable method for determining protein complex stoichiometry, quaternary structure, and spatial distribution in living cells using Förster resonance energy transfer (FRET) imaging. The method provides highly resolved spectra of molecules or molecular complexes at each image pixel, and it does so on a timescale shorter than that of molecular diffusion, which scrambles the spectral information. Acquisition of an entire spectrally resolved image, however, is slower than that of broad-bandwidth microscopes because it takes longer times to collect the same number of photons at each emission wavelength as in a broad bandwidth. Here, we demonstrate an optical micro-spectroscopic scheme that employs a laser beam shaped into a line to excite in parallel multiple sample voxels. The method presents dramatically increased sensitivity and/or acquisition speed and, at the same time, has excellent spatial and spectral resolution, similar to point-scan configurations. When applied to FRET imaging using an oligomeric FRET construct expressed in living cells and consisting of a FRET acceptor linked to three donors, the technique based on line-shaped excitation provides higher accuracy compared to the point-scan approach, and it reduces artifacts caused by photobleaching and other undesired photophysical effects.     

Factors affecting usefulness of triticale grain for bioethanol production

BACKGROUND: Triticale grain could be a useful material for bioethanol production. The aim of this study was to examine how grain cultivar, nitrogen fertilisation level, location and year affect the starch content in triticale grain and which method of starch determination, polarimetric, enzymatic or near‐infrared transmission (NIT), gives the best prediction of real bioethanol productivity from triticale grain. RESULTS: It was found that the starch content in triticale grain was correlated positively with test weight and 1000‐kernel weight but negatively with falling number and protein content. All factors, i.e. cultivar, nitrogen fertilisation level, location and year, as well as the intrinsic interaction between these factors, had a significant effect on the starch level in triticale grain. The NIT procedure of starch determination gave the best results in predicting the real yield of ethanol obtained on the basis of classic fermentation (95% match), while the enzymatic and polarimetric methods corresponded with the real results at levels of 89–90 and 78–82% respectively. CONCLUSION: Grain growth conditions related to location and nitrogen fertilisation level had the most noticeable effect on grain starch content, while grain yield per hectare had the most significant effect on ethanol productivity. Copyright © 2010 Society of Chemical Industry