Mastering the reactivity of gold (i) carbenes

Esta tesis doctoral se ha centrado en el estudio experimental de la ciclación catalizada por oro de 1,5-eninos con un grupo electroatractor en la posición alílica que permite obtener selectivamente 1,4-dienos o biciclo[3.1.0]hexenes modulando la electrofilia del catalizador. Mecanísticamente es una ciclación 5-endo-dig en la que se forma un ciclopropil carbeno de Au como intermedio, que a su vez puede reaccionar in situ con nucleófilos como H2O, ROH, aldehídos ó nucleófilos carbonados. También se estudió la adición de nucleófilos carbonados a los intermedios en la migración 1,2 y 1,3 de carboxilatos propargílicos catalizada por Au(I). Por otro se ha demostrado que la reacción intermolecular entre alquenos y alquinos catalizada por Au(I) es factible si se utilizan ligandos voluminosos de modo que el oro se coordine selectivamente al alquino. Es una reacción muy general y limpia que abre camino al desarrollo de nuevos procesos intermoleculares catalizados por oro. In this work, we have studied the gold(I)-catalyzed cyclization of 1,5-enynes bearing an electron-withdrawing group at the allylic position that allows to control its reactivity: 1,4-dienes or bicycle[3.1.0]hexenes can be obtained by tuning the electrophilicity of the gold catalyst. The proposed mechanism begins by 5-endo-dig cyclization to form gold(I) cyclopropyl intermediates that can be trapped in situ with nucleophiles like H2O, ROH, aldehydes or carbon nucleophiles (electron rich arenes and 1,3-dicarbonyl compounds). The addition of carbon nucleophiles to the intermediates of 1,2- and 1,3-rearrangement of propargyl carboxilates catalyzed by gold(I) has been also studied in this work. We also have shown that the intermolecular reaction between allenes and alkynes is feasible using gold(I) complexes with bulky ligands that selectively activate alkynes in the presence of alkenes, which opens opportunities for the development of new gold-catalyzed intermolecular processes

Elaboración de mermelada en base a Jackfruit (Artocarpus heterophyllus), maracuyá (passiflora edulis) y fibra.

The study sought to develop a new food product based Jackfruit, passion fruit and fiber; the last ingredient replaced the pectin (usually added to these products) getting a product of good quality and the desired characteristics of spreadability in jam. Although in the market there are a variety of jams, Jeleías is a new and innovated product that has functional properties. To determinate the appropriate concentration of fruit (jackfruit: passion fruit) and the right amount of fiber, has to made an experimental random design with factorial model 32 (9 treatments) and 3 replications. The better treatments were B (76.45% and 23.55% Jackfruit passion fruit fiber 0.2%), C (80% and 20% Jackfruit passion fruit fiber 0.2%) and E (76.45% and 23.55% Jackfruit passion fruit fiber 0.6% ),to meet the requirements of ° Brix, pH, penetrability, spreadability and pectin content. From these three prototypes, has to made a sensory evaluation study was done through a satisfaction test, making treatment B in the final formulation. A market research allowed to know opening the potential consumers of the product, considering whether they would consume this new jam, what price they would pay and know the places where they would like to buy. Finally, the physical and chemical analysis of final product, allowed to know that Jeleías is a good source of vitamin C and doesn´t contribute with fat to the diet.El presente trabajo buscó desarrollar un nuevo producto alimenticio en base a Jackfruit, maracuyá y fibra; este último ingrediente remplazó a la pectina (que normalmente se añade a este tipo de productos) obteniendo un producto de buena calidad y con las características deseadas de untabilidad en la mermelada. A pesar de que en el mercado existe una gran variedad de mermeladas, Jeléias es un producto nuevo, innovador y con propiedades funcionales. Para determinar la concentración adecuada de fruta (Jackfruit:maracuyá) y la cantidad adecuada de fibra, se realizó un diseño experimental completamente al azar con modelo factorial 32 (9 tratamientos) y tres repeticiones. Los mejores tratamientos fueron B (76.45% Jackfruit y 23.55% maracuyá; 0.2% de fibra), C (80% Jackfruit y 20% maracuyá; 0.2% de fibra) y E (76.45% Jackfruit y 23.55% maracuyá; 0.6% de fibra), por cumplir con los requisitos de °Brix, pH, penetrabilidad, contenido de pectina y untabilidad. A partir de estos tres prototipos, se realizó un estudio de evaluación sensorial mediante la prueba de grado de satisfacción, convirtiéndose el tratamiento B en la formulación final. Un estudio de mercado permitió conocer la apertura de los consumidores potenciales de este producto, considerando si estarían dispuestos a consumir esta nueva mermelada, qué precio pagarían y conocer los lugares donde les gustaría adquirirlo. Finalmente, los análisis físico-químicos del producto final, permitieron conocer que Jeléias es una buena fuente de vitamina C y no aporta con grasas a la dieta

The Principles of Gold-Catalyzed Molecular Gymnastics

L'or(I) dirigeix el contorsionisme molecular mitjançant reaccions intramoleculars i intermoleculars d'enins per mitjà d'intermedis ciclopropil o carbens altament distorsionats. La síntesi de productes naturals com (+)-orienalol F i (-)-englerin A mostra l'estat d'art de la catàlisi de l'or(I) per a construir complexitat molecular.Gold(I) orchestrates molecular gymnastics by intraand intermolecular reaction of enymes via highly distorted cyclopropyl gold carbenes as intermediates. The synthesis of natural products such as (+)-orientalol F and (−)-englerin A illustrates the state of the art of gold (I) catalysis for the buildup of molecular complexity

Age-related changes in creative thinking during late childhood: The contribution of cooperative learning

Creative thinking has been considered a human skill that is necessary for facing challenging situations that require adaptive solutions. From an educational perspective, creative thinking plays an important role in learning processes and is an issue of central importance within classroom methodology. In this regard, Cooperative learning (CL) has been studied as a methodology that enhances creative processes. CL methodology refers to teaching procedures based on organizing the class into small mixed-abilities groups where students work cooperatively to complete academic tasks and consolidate their learning. However, the impact of CL on creative thinking seems to have been insufficiently explored in late childhood, which is known as a transitory stage between childhood and adolescence. Using two tests (at 5th and 6th grades of Primary School), we examined the trajectory of creative thinking in fifty-three students from two different schools. Students were assessed by a divergent thinking task (CREA Test; Corbalán et al., 2015) at two time points: Test-1 (T1), with a mean age of 9.81 years (Sd= 0.48), and Test-2 (T2), with a mean age of 11.35 years (Sd= 0.52). Given the differences in methodology delivered in each school (Cooperative and individualistic learning), we also analyzed the effects of this variable on student creative thinking performance. We found significant improvements between testing in the two schools, although CL appeared to have a more positive effect than IL on creative thinking performance. Our finding highlights the importance of studying classroom methodology as a mediating factor in creative thinking development, which could be important in the learning processes as well as the integral development of the child

Development of executive functions in late childhood and the mediating role of cooperative learning: A longitudinal study

We examine the developmental changes in Executive functions (EFs) throughout late childhood and how the contextual factor of classroom methodology mediates such changes. Using data collected from fifty-three pupils at two time points (between the 5th and 6th grades of Primary School) we observed the longitudinal development of cool (Working Memory (WM), Cognitive Flexibility, Inhibitory Control, and Planning) and hot-EFs (Emotional Intelligence-EI-). The participants were selected from two schools with different methodological approaches (Cooperative and Individualistic learning) to examine the mediating role of classroom methodologies in developmental changes in EFs. The results revealed age-related improvements in performance on WM, cognitive flexibility, and planning tasks. Moreover, Cooperative Learning (CL) significantly affected performance on WM and self-control tasks. Our findings highlight the importance of studying the development of EFs at the end of the Primary School stage, since natural development involves numerous contextual factors that deserve attention, particularly for improving methodological proposals and learning processes

Preparation and Characterization of Kynurenic Acid Occluded in Sol-Gel Silica and SBA-15 Silica as Release Reservoirs

Kynurenic acid (KYNA) may have important therapeutic effects in neurological disorders; however, its use as a neuroprotective agent is restricted due to its very limited ability to cross the blood brain barrier (BBB). For this reason, we are looking for new alternatives for KYNA to reach the brain; one of them is using drug delivery systems. To obtain KYNA release reservoirs, KYNA molecules were hosted in two different silica materials. The different KYNA-silica materials were characterized by means of several physical techniques. The spectroscopic studies showed that KYNA molecules remained unchanged once hosted in silica materials. The surface area values of KYNA-silica samples were substantially lower than those for pure silica materials due to the addition of the drug. The electronic micrographs showed that the sol-gel KYNA-silica material consisted of aggregates of nanoparticles around 50 nm in size. On the other hand, the typical SBA-15 hexagonal arrangement was observed, even when hosting KYNA molecules. KYNA release profiles, carried out during approximately 300 hours, showed a first stage of fast drug release followed by a slow release phase. The experimental values fitted to the Peppas equation indicate that the release mechanism was controlled by Fickian diffusion

Cyclobutene vs 1,3-Diene Formation in the Gold-Catalyzed Reaction of Alkynes with Alkenes : The Complete Mechanistic Picture

The intermolecular gold(I)-catalyzed reaction between arylalkynes and alkenes leads to cyclobutenes by a [2 + 2] cycloaddition, which takes place stepwise, first by formation of cyclopropyl gold(I) carbenes, followed by a ring expansion. However, 1,3-butadienes are also formed in the case of ortho -substituted arylalkynes by a metathesis-type process. The corresponding reaction of alkenes with aryl-1,3-butadiynes, ethynylogous to arylalkynes, leads exclusively to cyclobutenes. A comprehensive mechanism for the gold(I)-catalyzed reaction of alkynes with alkenes is proposed on the basis of density functional theory calculations, which shows that the two pathways leading to cyclobutenes or dienes are very close in energy. The key intermediates are cyclopropyl gold(I) carbenes, which have been independently generated by retro-Buchner reaction from stereodefined 1a,7b-dihydro-1 H -cyclopropa[ a ]naphthalenes

Mechanical Properties and Antibacterial Effect on Mono-Strain of Streptococcus mutans of Orthodontic Cements Reinforced with Chlorhexidine-Modified Nanotubes

Recently, several studies have introduced nanotechnology into the area of dental materials with the aim of improving their properties. The objective of this study is to determine the antibacterial and mechanical properties of type I glass ionomers reinforced with halloysite nanotubes modified with 2% chlorhexidine at concentrations of 5% and 10% relative to the total weight of the powder used to construct each sample. Regarding antibacterial effect, 200 samples were established and distributed into four experimental groups and six control groups (4 +ve and 2 −ve), with 20 samples each. The mechanical properties were evaluated in 270 samples, assessing microhardness (30 samples), compressive strength (120 samples), and setting time (120 samples). The groups were characterized by scanning electron microscopy and Fourier transform infrared spectroscopy, and the antibacterial activity of the ionomers was evaluated on Streptococcus mutans for 24 h. The control and positive control groups showed no antibacterial effect, while the experimental group with 5% concentration showed a zone of growth inhibition between 11.35 mm and 11.45 mm, and the group with 10% concentration showed a zone of growth inhibition between 12.50 mm and 13.20 mm. Statistical differences were observed between the experimental groups with 5% and 10% nanotubes. Regarding the mechanical properties, microhardness, and setting time, no statistical difference was found when compared with control groups, while compressive strength showed higher significant values, with ionomers modified with 10% concentration of nanotubes resulting in better compressive strength values. The incorporation of nanotubes at concentrations of 5% and 10% effectively inhibited the presence of S. mutans, particularly when the dose–response relationship was taken into account, with the advantage of maintaining and improving their mechanical properties

HCV-coinfection is related to an increased HIV-1 reservoir size in cART-treated HIV patients: a cross-sectional study

In HIV-1/HCV-coinfected patients, chronic HCV infection leads to an increased T-lymphocyte immune activation compared to HIV-monoinfected patients, thereby likely contributing to increase HIV-1 reservoir that is the major barrier for its eradication. Our objective was to evaluate the influence of HCV coinfection in HIV-1 viral reservoir size in resting (r) CD4+ T-cells (CD25-CD69-HLADR-). Multicenter cross-sectional study of 97 cART-treated HIV-1 patients, including 36 patients with HIV and HCV-chronic co-infection without anti-HCV treatment, 32 HIV patients with HCV spontaneous clearance and 29 HIV-monoinfected patients. rCD4+ T-cells were isolated and total DNA was extracted. HIV viral reservoir was measured by Alu-LTR qPCR. Differences between groups were calculated with a generalized linear model. Overall, 63.9% were men, median age of 41 years and Caucasian. Median CD4+ and CD8+ T-lymphocytes were 725 and 858 cells/mm3, respectively. CD4+ T nadir cells was 305 cells/mm3. Proviral HIV-1 DNA size was significantly increased in chronic HIV/HCV-coinfected compared to HIV-monoinfected patients (206.21 ± 47.38 vs. 87.34 ± 22.46, respectively; P = 0.009), as well as in spontaneously clarified HCV co-infected patients when compared to HIV-monoinfected individuals (136.20 ± 33.20; P = 0.009). HIV-1/HCV co-infected patients showed a larger HIV-1 reservoir size in comparison to HIV-monoinfected individuals. This increase could lead to a greater complexity in the elimination of HIV-1 reservoir in HIV-1/HCV-coinfected individuals, which should be considered in the current strategies for the elimination of HIV-1 reservoir.The authors thank all the patients for their participation. Financial support was provided by the Instituto de Salud Carlos III to VB (PI15CIII/00031), by the Spanish Ministry of Economy and Competitiveness to MC (SAF2016–78480-R) and The SPANISH AIDS Research Network RD16CIII/0002/0001, RD16CIII/0002/0002 and RD16/0025/0013 - ISCIII – FEDER. MRLP is supported by ISCIII - Subdirección General de Evaluacion and European Funding for Regional Development (FEDER) (PIE 13/00040 and RD12/0017/0017 RETIC de SIDA). C.P. is supported by the Portuguese Fundação para a Ciência e Tecnologia (FCT) (grant number SFRH/BPD/77448/2011 is part of the EDCTP2 programme supported by the European Union). V.B., A.F.R. and N.R. are supported by the Miguel Servet programme from Fondo de Investigación Sanitaria (ISCIII) (grant number CP13/00098, CP14/CIII/00010 and CP14/00198, respectively).S

A Large Multicenter Prospective Study of Community-Onset Healthcare Associated Bacteremic Urinary Tract Infections in the Era of Multidrug Resistance: Even Worse than Hospital Acquired Infections?

Introduction: Healthcare-associated (HCA) infections represent a growing public health problem. The aim of this study was to compare community-onset healthcare associated (CO-HCA) bacteremic urinary tract infections (BUTI) and hospital-acquired (HA)-BUTI with special focus on multidrug resistances (MDR) and outcomes. Methods: ITUBRAS-project is a prospective multicenter cohort study of patients with HCA-BUTI. All consecutive hospitalized adult patients with CO-HCA-BUTI or HA-BUTI episode were included in the study. Exclusion criteria were: patients < 18 years old, non-hospitalized patients, bacteremia from another source or primary bacteremia, non-healthcare-related infections and infections caused by unusual pathogens of the urinary tract. The main outcome variable was 30-day all-cause mortality with day 1 as the first day of positive blood culture. Logistic regression was used to analyze factors associated with clinical cure at hospital discharge and with receiving inappropriate initial antibiotic treatment. Cox regression was used to evaluate 30-day all-cause mortality. Results: Four hundred forty-three episodes were included, 223 CO-HCA-BUTI. Patients with CO-HCA-BUTI were older (p < 0.001) and had more underlying diseases (p = 0.029) than those with HA-BUTI. The severity of the acute illness (Pitt score) was also higher in CO-HCA-BUTI (p = 0.026). Overall, a very high rate of MDR profiles (271/443, 61.2%) was observed, with no statistical differences between groups. In multivariable analysis, inadequate empirical treatment was associated with MDR profile (aOR 3.35; 95% CI 1.77–6.35), Pseudomonas aeruginosa (aOR 2.86; 95% CI 1.27–6.44) and Charlson index (aOR 1.11; 95% CI 1.01–1.23). Mortality was not associated with the site of acquisition of the infection or the presence of MDR profile. However, in the logistic regression analyses patients with CO-HCA-BUTI (aOR 0.61; 95% CI 0.40–0.93) were less likely to present clinical cure. Conclusion: The rate of MDR infections was worryingly high in our study. No differences in MDR rates were found between CO-HCA-BUTI and HA-BUTI, in the probability of receiving inappropriate empirical treatment or in 30-day mortality. However, CO-HCA-BUTIs were associated with worse clinical cure. © 2021, The Author(s)