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

Prevalence and clonality of methicillin-resistant Staphylococcus aureus (MRSA) in the Atlantic Azores islands: predominance of SCCmec types IV, V and VI

In order to obtain insights into the methicillin-resistant Staphylococcus aureus (MRSA) population structure in the Azores archipelago, 106 MRSA isolates were collected from patients attending an Azorean central hospital between January 2007 and February 2008. Antimicrobial resistance was determined for all isolates. Molecular typing was performed by pulsed-field gel electrophoresis (PFGE), spa typing, multilocus sequence typing (MLST), staphylococcal chromosome cassette mec (SCCmec) typing and the presence of Panton–Valentine leukocidin (PVL). The majority of the isolates (87%, n = 92) belonged to the EMRSA-15 clone (ST22, SCCmec-IVh), followed by the Pediatric clone (ST5-VI/IVc) (11%, n = 12). The Berlin clone (ST45-IVa) and a new clone (spa type t1839, ST1339 and SCCmec V variant) were represented by single isolates. All of the isolates carried SCCmec types IV, V or VI and a non-multiresistant antibiotic profile, resembling the currently emerging community MRSA. Moreover, PVL was described for the first time to be associated with the Pediatric clone carrying SCCmec type VI. We provided the first description of the population structure of MRSA in the Azores islands, which seems to be shaped by genetic events occurring locally, as well as by the regular population exchange between the islands, continental Portugal, the United Kingdom and the United States

Staphylococcus aureus in former Portuguese colonies from Africa and the Far East: missing data to help fill the world map

AbstractThe aim of the present study was to determine the prevalence and risk factors for methicillin-resistant Staphylococcus aureus (MRSA) nasal carriage among patients and healthcare workers in Angola (ANG), São Tomé and Príncipe (STP), Cape Verde (CV) and East Timor (ET), and to characterize the antimicrobial susceptibility, virulence content and population structure of all S. aureus. Despite the importance of MRSA as a major human pathogen, data from these former Portuguese colonies in Africa and Asia are scarce. A total of 2065 nasal swabs recovered between 2010–14 were included in the study. Antimicrobial susceptibility testing and molecular characterization of S. aureus showed: (i) a very high MRSA prevalence in ANG (61.6%), moderate in STP (25.5%), low in CV (5.6%) and null in ET; (ii) a high prevalence of Panton–Valentine leukocidin in STP (36.8%), ET (29.2%) and CV (28.3%) contrasting with ANG (7.9%); (iii) ST5-SCCmecIVa, ST8-IV/V and ST5-VI were the major MRSA clones in ANG (65.2%), STP (44.8%) and CV (50%), respectively; (iv) a high resistance to trimethoprim-sulfamethoxazole in ANG (66.5%) and STP (50.9%), to rifampin in ANG (77.3%), and to tetracycline in STP (26.3%) and ET (20.8%); (v) three major methicillin-susceptible S. aureus clones (ST15, ST508, ST152) were present in all four countries. Age <18 years (OR 2.03, 95% CI 1.24–3.31), previous surgery (OR 2.45, 95% CI 1.24–4.83), no smoking (OR 4.04, 95% CI 1.05–15.50), and longer hospitalization (OR 2.53, 95% CI 1.49–4.28) were risk factors for MRSA carriage. This study provided the first comprehensive overview on MRSA in former Portuguese colonies in Africa and Asia, missing data in the world map

Theoretical and experimental studies of aryl-bithiophene based push-pull pi-conjugated heterocyclic systems bearing cyanoacetic or rhodanine-3-acetic acid acceptors for SHG nonlinear optical applications

A series of push-pull aryl-bithiophene based systems 2-3 were designed and synthesized in order to understand how structural modifications influence the electronic, linear and nonlinear optical properties. The push-pull conjugated chromophores 2-3 bear a bithiophene spacer conjugated with a phenyl ring functionalized with N,N-dialkylamino electron-donor groups together with cyanoacetic or rhodanine-3-acetic acid acceptor groups. Theoretical (DFT calculations) and experimental studies were carried out to obtain information on conformation, electronic structure, electron distribution, dipolar moment, and molecular nonlinearity response of the push-pull bithiophene derivatives. This multidisciplinary study revealed that chromophore 2e exhibits the highest value for hyperpolarizability beta (10440 × 10-30 esu) due to the strong electron donating ability of the N,N-diethylamino group, and the ethyne linker that not only lengthens the pi- conjugation path but also grants less distortion to the system.Thanks are due to Fundação para a Ciência e Tecnologia (FCT) for a PhD grant to S. S. M. Fernandes (SFRH/BD/87786/2012) and FEDERCOMPETE for financial support through the CQ/UM (Ref. UID/QUI/ 00686/2013 and UID/QUI/0686/2016). The NMR spectrometer Bruker Avance III 400 is part of the National NMR Network and was purchased within the framework of the National Program for Scientific Reequipment, contract REDE/1517/RMN/2005 with funds from POCI 2010 (FEDER) and FCT. 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 FEDERCOMPETE. 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) and co-financed by the ERDF under the PT2020 Partnership Agreement (POCI-01-0145-FEDER–007265).info:eu-repo/semantics/publishedVersio

High Rate of MCR-1-Producing Escherichia coli and Klebsiella pneumoniae among Pigs, Portugal.

The mcr-1 (mobile colistin resistance 1) gene, which encodes phosphoethanolamine transferase, has been recently identified as a source of acquired resistance to polymyxins in Escherichia coli. Using the SuperPolymyxin selective medium, we prospectively screened 100 pigs at 2 farms in Portugal for polymyxin-resistant Enterobacteriaceae and recovered 98 plasmid-mediated MCR-1-producing isolates. Most isolates corresponded to nonclonally related E. coli belonging to many sequence types; we also found 2 Klebsiella pneumoniae sequence types. The mcr-1 gene was carried on IncHI2 or IncP plasmid backbones. Our finding of a high rate of MCR-1 producers on 2 pig farms in Portugal highlights the diffusion of that colistin-resistance determinant at the farm level. The fact that the pigs received colistin as metaphylaxis in their feed during the 6 weeks before sampling suggests selective pressure

Team-Based Learning in Chemistry Courses with Laboratory Sessions

[EN] The implementation of Team-Based Learning (TBL, http://www.teambasedlearning.org) in one-semester undergraduate courses of chemistry offered to first year students is reported. TBL is an active learning instructional strategy heavily relying on small group interaction. Teaching lab classes in a TBL context presented a specific challenge, as decisions were required about their role in the global framework and the possibility of incorporating lab activities as “teamwork”. The design of lab sessions as TBL team application activities is here also illustrated, both for a course of General Chemistry and a course of Organic Chemistry. TBL dramatically improved students class attendance and participation. Its implementation has provided a unique opportunity for the pedagogical development of teaching staff. A moderate number of students reported discomfort with TBL: the requirement of individual preparation before classes and the impact of team participation in the final grade is indeed a new ground for most students, often perceived as a troubling deviation from the common social paradigm of the learning process. The role of the instructor as a facilitator of individual and team work, and the clear explanation of the method are thus of utmost relevance.The authors thank Faculdade de Ciências e Tecnologia (Universidade Nova de Lisboa) for financial supportAires-De-Sousa, J.; Cardoso, MM.; Ferreira, L.; Lima, J.; Noronha, J.; Nunes, A.; Ponte, M. (2017). Team-Based Learning in Chemistry Courses with Laboratory Sessions. En Proceedings of the 3rd International Conference on Higher Education Advances. Editorial Universitat Politècnica de València. 1213-1218. https://doi.org/10.4995/HEAD17.2017.5559OCS1213121

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

High prevalence of ST121 in community-associated methicillin-susceptible Staphylococcus aureus lineages responsible for skin and soft tissue infections in Portuguese children

In order to evaluate the incidence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in Portugal, we analyzed a collection of 38 S. aureus isolates recovered from 30 children attending the pediatric emergency department of a central hospital in Lisbon due to skin and soft tissue infections. Molecular characterization identified seven clonal lineages among the 35 methicillin-susceptible S. aureus (MSSA) isolates, of which the major lineage PFGE A/t159/ST121 included 63% of the isolates. The three MRSA isolates belonged to the Pediatric clone PFGE D/t535/ST5-IV (n = 2) and to the European CA-MRSA clone PFGE G/t044/ST80-IVc (n = 1). All isolates harbored several virulence factors, namely, leukocidins. Panton-Valentine leukocidin (PVL) was produced by isolates from five MSSA lineages and by the ST80 MRSA. Of interest, this is the first reported isolation of CA-MRSA ST80 in Portugal

Molecular Analysis of Repeated Methicillin-Resistant Staphylococcus aureus Infections in Children

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen that causes severe morbidity and mortality in hospitalized patients. It is unclear whether repeated MRSA infections in pediatric patients are caused by relapse of previous infecting strains or by acquiring new strains from extrinsic sources. The study aimed to define the genetic relatedness of MRSA isolates from children with repeated infections. METHODOLOGY/PRINCIPAL FINDINGS: Children with multiple MRSA infections during 2004-2006 were identified in a teaching hospital. Repeated infections were confirmed by chart review and the responsible isolates were genotyped and screened for Panton-Valentine leukocidin (PVL) genes. Two consecutive episodes comprised an infection pair, and strain relatedness was defined for each pair as indistinguishable, highly related, or distinct if the isolates were of the same subtype, the same genotype, or different genotype, respectively. A total of 114 episodes comprising 66 infection pairs were identified in 48 children. The interval of infection pairs ranged from 15 days to 346 days, with a median duration of 57.5 days. Genotypings classified all isolates into 7 genotypes and 31 subtypes. Of 66 pairs, 46 (69.7%), 13 (19.7%) and 7 (10.6%) pairs were caused by indistinguishable, highly related and distinct strains, respectively. Subsequent infections caused by indistinguishable strains were more common for PVL-positive strains (17/18, 94.4%) than for PVL-negative strains (29/48, 60.4%, P = 0.007). The strain relatedness was not affected by the durations of interval between infections. CONCLUSIONS/SIGNIFICANCE: Most repeated MRSA infections in children are caused by indistinguishable strains even after a long period of interval, suggesting that persistent carriage and relapse of initial infecting strains were responsible for the majority of recurrent MRSA infections

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