High-valent bismuth redox catalysis

In the last years, bismuth has transitioned from being considered a mere Lewis acid catalyst to being recognised as an interesting redox catalyst for organic synthesis. A rational design of a ligand scaffold for the Bi center resulted in a robust catalytic system applicable to various bismuth redox processes

Fluorination of arylboronic esters enabled by bismuth redox catalysis

Bismuth catalysis has traditionally relied on the Lewis acidic properties of the element in a fixed oxidation state. In this paper, we report a series of bismuth complexes that can undergo oxidative addition, reductive elimination, and transmetallation in a manner akin to transition metals. Rational ligand optimization featuring a sulfoximine moiety produced an active catalyst for the fluorination of aryl boronic esters through a bismuth (III)/bismuth (V) redox cycle. Crystallographic characterization of the different bismuth species involved, together with a mechanistic investigation of the carbon-fluorine bond-forming event, identified the crucial features that were combined to implement the full catalytic cycle

Mechanism of the Aryl-F Bond-Forming Step from Bi(V) Fluorides.

In this article, we describe a combined experimental and theoretical mechanistic investigation of the C(sp2)-F bond formation from neutral and cationic high-valent organobismuth(V) fluorides, featuring a dianionic bis-aryl sulfoximine ligand. An exhaustive assessment of the substitution pattern in the ligand, the sulfoximine, and the reactive aryl on neutral triarylbismuth(V) difluorides revealed that formation of dimeric structures in solution promotes facile Ar-F bond formation. Noteworthy, theoretical modeling of reductive elimination from neutral bismuth(V) difluorides agrees with the experimentally determined kinetic and thermodynamic parameters. Moreover, the addition of external fluoride sources leads to inactive octahedral anionic Bi(V) trifluoride salts, which decelerate reductive elimination. On the other hand, a parallel analysis for cationic bismuthonium fluorides revealed the crucial role of tetrafluoroborate anion as fluoride source. Both experimental and theoretical analyses conclude that C-F bond formation occurs through a low-energy five-membered transition-state pathway, where the F anion is delivered to a C(sp2) center, from a BF4 anion, reminiscent of the Balz-Schiemann reaction. The knowledge gathered throughout the investigation permitted a rational assessment of the key parameters of several ligands, identifying the simple sulfone-based ligand family as an improved system for the stoichiometric and catalytic fluorination of arylboronic acid derivatives

Evidencias farmacológicas de la participación del sistema opioide endógeno en la respuesta inflamatoria local de la pata de la rata

Hemos investigado el papel del sistema opioide endógeno (SOE) en la respuesta inflamatoria inducida por la inyección subplantar (SP) de salino (SS) y carragenina (CA) en la pata trasera de la rata. Se usó naloxona intraperitoneal (IP) para desenmascarar los efectos de los opiáceos endógenos liberados durante la inflamación periférica. Tres grupos de ratas recibieron uno de los siguientes tratamientos SP: SS, CA o ninguna inyección (NI). En condiciones basales y 3 horas después del tratamiento fueron evaluados el umbral del dolor por presión (PPT), el volúmen de la pata (edema) y la temperatura local. En cada grupo fueron también investigados los efectos del vehículo IP, naloxona y (+)-naloxona (0,1 mg/kg). Los grupos SS y CA indujeron una significativa respuesta inflamatoria con hiperalgesia, edema e hiperemia local. La administración IP de naloxona pero no de (+)-naloxona, 15 minutos antes de la prueba, incrementó significativamente el edema en todos los grupos de tratamiento (p< 0,05) sin alterar el PPT o la temperatura local. El ANOVA de dos vías, reveló que el tratamiento y los fármacos, así como sus interacciones tenían un impacto significativo en el edema el cual estaba relacionado con los efectos de la CA y la naloxona. Nuestros hallazgos ilustran la implicación del sistema opioide endógeno a la respuesta fisiológica a la lesión local, regulando la fuga microvascular en los tejidos inflamados

Phosphorylated c-Src in the nucleus is associated with improved patient outcome in ER-positive breast cancer

Elevated c-Src protein expression has been shown in breast cancer and &lt;i&gt;in vitro&lt;/i&gt; evidence suggests a role in endocrine resistance. To investigate whether c-Src is involved in endocrine resistance, we examined the expression of both total and activated c-Src in human breast cancer specimens from a cohort of oestrogen receptor (ER)-positive tamoxifen-treated breast cancer patients. Tissue microarray technology was employed to analyse 262 tumour specimens taken before tamoxifen treatment. Immunohistochemistry using total c-Src and activated c-Src antibodies was performed. Kaplan–Meier survival curves were constructed and log-rank test were performed. High level of nuclear activated Src was significantly associated with improved overall survival (&lt;i&gt;P&lt;/i&gt;=0.047) and lower recurrence rates on tamoxifen (&lt;i&gt;P&lt;/i&gt;=0.02). Improved patient outcome was only seen with activated Src in the nucleus. Nuclear activated Src expression was significantly associated with node-negative disease and a lower NPI (&lt;i&gt;P&lt;/i&gt;&#60;0.05). On subgroup analysis, only ER-positive/progesterone receptor (PgR)-positive tumours were associated with improved survival (&lt;i&gt;P&lt;/i&gt;=0.004). This shows that c-Src activity is increased in breast cancer and that activated Src within the nucleus of ER-positive tumours predicts an improved outcome. In ER/PgR-positive disease, activated Src kinase does not appear to be involved in &lt;i&gt;de novo&lt;/i&gt; endocrine resistance. Further study is required in ER-negative breast cancer as this may represent a cohort in which it is associated with poor outcome

Elaboració d'una guia sobre aprenentatge cooperatiu a la Universitat de Girona

L’any 2009, l’Institut de Ciències de l’Educació Josep Pallach de la Universitat de Girona va impulsar la creació de diverses Xarxes d’Innovació Docent (XID). Aquestes xarxes agrupen professors de disciplines diverses que volen compartir experiències relatives a la millora docent. Una d’aquestes xarxes és la relativa a l’Aprenentatge Cooperatiu (XIDAC). Es compon de vuit professors que utilitzen aquest mètode d’aprenentatge a la seva docència. Un dels seus objectius és produir una guia o petit manual sobre aprenentatge cooperatiu (AC) a la UdG. Es tracta d’orientar els professors que vulguin posar- lo en pràctica, o que ja ho estiguin fent i necessitin un material de suport. A la present comunicació es descriu el procés d’elaboració d’aquesta guia. En primer lloc, s’exposen característiques de la UdG que poden determinarne en algun sentit el perfil i continguts. Després, es resumeixen els resultats d’entrevistes amb professors que apliquen l’AC tot i no pertànyer a la Xarxa. A continuació, es resumeixen els resultats d’una enquesta elaborada al professorat de la UdG (actualment està en fase de resposta). Amb posterioritat, es fa una presentació general de la futura guia i es descriu breument un exemple de fitxa d’activitat d’AC. Finalment, es fa referència al procés de debat obert de part d’aquests continguts a través d’una pàgina web, per tal de recollir punts de vista externs i millorar la proposta.Peer Reviewe

Thermal Stabilization of an Endoglucanase by Cyclization

An intein-driven protein splicing approach allowed for the covalent linkage between the N- and C-termini of a polypeptide chain to create circular variants of the endo-β-1,3-1,4-glucanase, LicA, from Bacillus licheniformis. Two circular variants, LicA-C1 and LicA-C2, which have connecting loops of 20 and 14 amino acids, respectively, showed catalytic activities that are approximately two and three times higher, respectively, compared to that of the linear LicA (LicA-L1). The thermal stability of the circular variants was significantly increased compared to the linear form. Whereas the linear glucanase lost half of its activity after 3 min at 65 °C, the two circular variants have 6-fold (LicA-C1) and 16-fold (LicA-C2) increased half-life time of inactivation. In agreement with this, fluorescence spectroscopy and differential scanning calorimetry studies revealed that circular enzymes undergo structural changes at higher temperatures compared to that of the linear form. The effect of calcium on the conformational stability and function of the circular LicAs was also investigated, and we observed that the presence of calcium ions results in increased thermal stability. The impact of the length of the designed loops on thermal stability of the circular proteins is discussed, and it is suggested that cyclization may be an efficient strategy for the increased stability of proteins

Accurate ab initio spin densities

We present an approach for the calculation of spin density distributions for molecules that require very large active spaces for a qualitatively correct description of their electronic structure. Our approach is based on the density-matrix renormalization group (DMRG) algorithm to calculate the spin density matrix elements as basic quantity for the spatially resolved spin density distribution. The spin density matrix elements are directly determined from the second-quantized elementary operators optimized by the DMRG algorithm. As an analytic convergence criterion for the spin density distribution, we employ our recently developed sampling-reconstruction scheme [J. Chem. Phys. 2011, 134, 224101] to build an accurate complete-active-space configuration-interaction (CASCI) wave function from the optimized matrix product states. The spin density matrix elements can then also be determined as an expectation value employing the reconstructed wave function expansion. Furthermore, the explicit reconstruction of a CASCI-type wave function provides insights into chemically interesting features of the molecule under study such as the distribution of $\alpha$- and $\beta$-electrons in terms of Slater determinants, CI coefficients, and natural orbitals. The methodology is applied to an iron nitrosyl complex which we have identified as a challenging system for standard approaches [J. Chem. Theory Comput. 2011, 7, 2740].Comment: 37 pages, 13 figure