Synthesis of pyridazine derivatives by Suzuki-Miyaura cross-coupling reaction and evaluation of their optical and electronic properties through experimental and theoretical studies

A series of π-conjugated molecules based on pyridazine and thiophene heterocycles 3a-e were synthesized using commercially or readily available coupling components, through a palladium catalyzed Suzuki-Miyaura cross-coupling reaction. The electron-deficient pyridazine heterocycle is functionalized by a thiophene electron-rich heterocycle at position 6 and different (hetero)aromatic moieties (phenyl, thienyl, furanyl) are functionalized with electron acceptor groups at position 3. DFT calculations were carried out to obtain information on the conformation, electronic structure, electron distribution, dipolar moment, and molecular nonlinear response of the synthesized push-pull pyridazine derivatives. Hyper-Rayleigh scattering in 1,4-dioxane solutions using a fundamental wavelength of 1064 nm was used to evaluate their second-order nonlinear optical properties. The thienylpyridazine functionalized with the cyano-phenyl moiety exhibited the largest first hyperpolarizability (beta = 175 × 10-30 esu, using the T convention) indicating its potential as a second harmonic generation (SHG) chromophore.The authors thank the Fundação para a Ciência e Tecnologia (Portugal) and FEDER-COMPETE for financial support through the Centro de Química and Centro de Física das Universidades do Minho e do Porto in the framework of the Strategic Funding (UID/QUI/0686/2016 and UID/FIS/04650/2013). Thanks are also due to Fundação para a Ciência e Tecnologia (FCT) for a Ph.D. grant to Sara S. M. Fernandes (SFRH/BD/87786/2012). This work was also supported by the Associated Laboratory for Sustainable Chemistry—Clean Processes and Technologies—LAQV which is financed by Portuguese national funds from FCT/MEC (UID/QUI/50006/2013) andco-financedbytheERDFunderthePT2020PartnershipAgreement(POCI-01-0145-FEDER–007265). TheNMR spectrometers are part of the National NMR Network (PTNMR) and are partially supported by Infrastructure Project Nº 022161 (co-financed by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC). The pulsed laser system was acquired within the framework of the grant (PTDC/CTM/105597/2008) from the Fundação para a Ciência e Tecnologia (FCT) with funding from FEDER-COMPETE.info:eu-repo/semantics/publishedVersio

Asymmetric synthesis of N-aryl aziridines

The reactions of a variety of N-arylhydroxamates as nitrogen transfer reagents to acryloyl derivatives of (−)-8-phenylmenthol, (−)-quinine and (−)-Oppolzer’s sultam acting as Michael acceptors was studied. Poor to modest diastereoselection was observed in the formation of aziridines. The absolute structure of one of the pure diastereomers secured from Oppolzer’s auxiliary was established by X-ray crystallography and hence the absolute configuration of the derived methyl-N-phenylaziridine-2-carboxylate could be assigned. Whilst only poor facial selectivity was observed for chiral hydroxamic acid prepared from dehydroabietic acid, moderate to good enantioselection of aziridines could be achieved with the chiral quaternary salts based on cinchona alkaloids, especially with that of cinchonine. A model is presented to explain the origin of enantioselection and a mechanism is proposed for the aziridination reaction

Expert system for predicting reaction conditions: The Michael reaction case

© 2015 American Chemical Society. A generic chemical transformation may often be achieved under various synthetic conditions. However, for any specific reagents, only one or a few among the reported synthetic protocols may be successful. For example, Michael β-addition reactions may proceed under different choices of solvent (e.g., hydrophobic, aprotic polar, protic) and catalyst (e.g., Brønsted acid, Lewis acid, Lewis base, etc.). Chemoinformatics methods could be efficiently used to establish a relationship between the reagent structures and the required reaction conditions, which would allow synthetic chemists to waste less time and resources in trying out various protocols in search for the appropriate one. In order to address this problem, a number of 2-classes classification models have been built on a set of 198 Michael reactions retrieved from literature. Trained models discriminate between processes that are compatible and respectively processes not feasible under a specific reaction condition option (feasible or not with a Lewis acid catalyst, feasible or not in hydrophobic solvent, etc.). Eight distinct models were built to decide the compatibility of a Michael addition process with each considered reaction condition option, while a ninth model was aimed to predict whether the assumed Michael addition is feasible at all. Different machine-learning methods (Support Vector Machine, Naive Bayes, and Random Forest) in combination with different types of descriptors (ISIDA fragments issued from Condensed Graphs of Reactions, MOLMAP, Electronic Effect Descriptors, and Chemistry Development Kit computed descriptors) have been used. Models have good predictive performance in 3-fold cross-validation done three times: balanced accuracy varies from 0.7 to 1. Developed models are available for the users at http://infochim.u-strasbg.fr/webserv/VSEngine.html. Eventually, these were challenged to predict feasibility conditions for ∼50 novel Michael reactions from the eNovalys database (originally from patent literature)

Population Structure of a Hybrid Clonal Group of Methicillin-Resistant Staphylococcus aureus, ST239-MRSA-III

The methicillin-resistant Staphylococcus aureus (MRSA) clonal group known as ST239-MRSA-III is notable for its hybrid origin and for causing sustained hospital epidemics worldwide since the late 1970s. We studied the population structure of this MRSA clonal group using a sample of 111 isolates that were collected over 34 years from 29 countries. Genetic variation was assessed using typing methods and novel ascertainment methods, resulting in approximately 15 kb of sequence from 32 loci for all isolates. A single most parsimonious tree, free of homoplasy, partitioned 28 haplotypes into geographically-associated clades, including prominent European, Asian, and South American clades. The rate of evolution was estimated to be approximately 100× faster than standard estimates for bacteria, and dated the most recent common ancestor of these isolates to the mid-20th century. Associations were discovered between the ST239 phylogeny and the ccrB and dru loci of the methicillin resistance genetic element, SCCmec type III, but not with the accessory components of the element that are targeted by multiplex PCR subtyping tools. In summary, the evolutionary history of ST239 can be characterized by rapid clonal diversification that has left strong evidence of geographic and temporal population structure. SCCmec type III has remained linked to the ST239 chromosome during clonal diversification, but it has undergone homoplasious losses of accessory components. These results provide a population genetics framework for the precise identification of emerging ST239 variants, and invite a re-evaluation of the markers used for subtyping SCCmec

Antibody responses in furunculosis patients vaccinated with autologous formalin-killed Staphylococcus aureus

Autologous vaccines (short: autovaccines) have been used since the beginning of the 20th century to treat chronic staphylococcal infections, but their mechanisms of action are still obscure. This prospective pilot study involved four patients with furunculosis who were vaccinated with autologous formalin-killed Staphylococcus aureus cells. Vaccines were individually prepared from the infecting S. aureus strain and repeatedly injected subcutaneously in increasing doses over several months. We characterized the virulence gene repertoire and spa genotype of the infecting and colonising S. aureus strains. Serum antibody responses to secreted and surface-bound bacterial antigens were determined by two-dimensional immunoblotting and flow-cytometry based assays (Luminex®). All patients reported clinical improvement. Molecular characterization showed that all strains isolated from one patient over time belonged to the same S. aureus clone. Already before treatment, there was robust antibody binding to a broad range of staphylococcal antigens. Autovaccination moderately boosted the IgG response to extracellular antigens in two patients, while the antibody response of the other two patients was not affected. Similarly, vaccination moderately enhanced the antibody response against some staphylococcal surface proteins, e.g. ClfA, ClfB, SdrD and SdrE. In summary, autovaccination only slightly boosted the pre-existing serum antibody response, predominantly to bacterial surface antigens

Online chemical modeling environment (OCHEM): web platform for data storage, model development and publishing of chemical information

The Online Chemical Modeling Environment is a web-based platform that aims to automate and simplify the typical steps required for QSAR modeling. The platform consists of two major subsystems: the database of experimental measurements and the modeling framework. A user-contributed database contains a set of tools for easy input, search and modification of thousands of records. The OCHEM database is based on the wiki principle and focuses primarily on the quality and verifiability of the data. The database is tightly integrated with the modeling framework, which supports all the steps required to create a predictive model: data search, calculation and selection of a vast variety of molecular descriptors, application of machine learning methods, validation, analysis of the model and assessment of the applicability domain. As compared to other similar systems, OCHEM is not intended to re-implement the existing tools or models but rather to invite the original authors to contribute their results, make them publicly available, share them with other users and to become members of the growing research community. Our intention is to make OCHEM a widely used platform to perform the QSPR/QSAR studies online and share it with other users on the Web. The ultimate goal of OCHEM is collecting all possible chemoinformatics tools within one simple, reliable and user-friendly resource. The OCHEM is free for web users and it is available online at http://www.ochem.eu

Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02

Fusidic acid and clindamycin resistance in community-associated, methicillin-resistant Staphylococcus aureus infections in children of Central Greece

<p>Abstract</p> <p>Introduction</p> <p>In Greece, fusidic acid and clindamycin are commonly used for the empiric therapy of suspected staphylococcal infections.</p> <p>Methods</p> <p>The medical records of children examined at the outpatient clinics or admitted to the pediatric wards of the University General Hospital of Larissa, Central Greece, with community-associated staphylococcal infections from January 2003 to December 2009 were reviewed.</p> <p>Results</p> <p>Of 309 children (0-14 years old), 21 (6.8%) had invasive infections and 288 (93.2%) skin and soft tissue infections (SSTIs). Thirty-five patients were ≤30 days of age. The proportion of staphylococcal infections caused by a community-associated methicillin-resistant <it>Staphylococcus aureus </it>(CA-MRSA) isolate increased from 51.5% (69 of 134) in 2003-2006 to 63.4% (111 of 175) in 2007-2009 (<it>P </it>= 0.037). Among the CA-MRSA isolates, 88.9% were resistant to fusidic acid, 77.6% to tetracycline, and 21.1% to clindamycin. Clindamycin resistance increased from 0% (2003) to 31.2% (2009) among the CA-MRSA isolates (<it>P </it>= 0.011). Over the 7-year period, an increase in multidrug-resistant CA-MRSA isolates was observed (<it>P </it>= 0.004). One hundred and thirty-one (93.6%) of the 140 tested MRSA isolates were Panton-Valentine leukocidin-positive. Multilocus sequence typing of 72 CA-MRSA isolates revealed that they belonged to ST80 (n = 61), ST30 (n = 6), ST377 (n = 3), ST22 (n = 1), and ST152 (n = 1). Resistance to fusidic acid was observed in ST80 (58/61), ST30 (1/6), and ST22 (1/1) isolates.</p> <p>Conclusion</p> <p>In areas with high rate of infections caused by multidrug-resistant CA-MRSA isolates, predominantly belonging to the European ST80 clone, fusidic acid and clindamycin should be used cautiously as empiric therapy in patients with suspected severe staphylococcal infections.</p

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns