Self-assembly and properties of a discrete water-soluble Prussian blue analogue FeII/CoIII cube: confinement of a water molecule in aqueous solution

Novel types of water-soluble anionic cubic cages, K4[{CoIII(Me3-Tacn)}4{FeII(CN)6}4] and Na4[{CoIII(Me3-Tacn)}4{FeII(CN)6}4] (Me3-Tacn = 1,4,7-trimethyl-1,4,7-triazacyclononane), were prepared by means of a mechanistically designed self-assembly process between [Co(Me3-Tacn)Cl3] and A4[FeII(CN)6] (M = Na or K), consisting of a rate-limiting outer-sphere redox step, followed by a fast substitution/inner-sphere redox reaction sequence. These compounds show remarkable stability in aqueous solution at different pH ranges, displaying neat protonation processes and reversible oxidation with peroxodisulfate to its neutral {FeIII4CoIII4} form. Furthermore, the cages behave as a robust and water-soluble molecular Prussian Blue analogue capable of encapsulating {Na-OH2}+ pairs and K+ cations in aqueous solution, with the cubic structure of the complex being preserved. Substitution of the {Na-OH2}+ pairs by K+ is easily accomplished, and the electrochemical properties of the sodium and potassium salts of the new cages have been found to be dramatically dependent on the encapsulated units

Plan de Actuación de Enfermería sobre hábitos saludables en nutrición y ejercicio físico en Consulta de Atención Primaria

INTRODUCCIÓN La obesidad y el sobrepeso son estados patológicos del individuo que en la actualidad son un grave problema sanitario, más de mil millones de personas en el mundo sufren sobrepeso y la tendencia sigue en aumento considerándose una pandemia a nivel global. Se puede definir como el exceso o acumulación de grasa en el organismo que produce efectos negativos y perjudiciales en la salud, teniendo una repercusión directa en enfermedades graves como diabetes, hipertensión, procesos metabólicos, cáncer u otras menos significativas. Por el momento no existe ninguna terapia singular y efectiva para paliar el aumento de la prevalencia de esta enfermedad, la tendencia actual y que pone de acuerdo a todos los estamentos sanitarios es que, la prevención mediante la promoción y mantenimiento de los hábitos de vida saludables en la población es la estrategia mas efectiva y eficiente. OBJETIVO Reducir el sobrepeso y la obesidad y promover hábitos higiénico-dietéticos desde la consulta de Enfermería de Atención Primaria fomentando su asimilación con los mínimos recursos, de modo natural y permanente, mediante el diseño de un plan de actuación de Enfermería. METODOLOGIA Se realizó una revisión bibliográfica sobre las recomendaciones para prevenir y/o actuar ante la obesidad y sobrepeso desde Anteción Primaria y unas entrevistas personalizadas y semiestructuradas en dos Centros de Salud con los profesionales relacionados con la asistencia en estas áreas. Posteriormente se diseñó un plan de actuación de Enfermería para ofrecer unas recomendaciones básicas a profesionales y usuarios/as en base a la revisión bibliográfica y las aportaciones de las y los profesionales, seleccionando aquellas recomendaciones más económicas, sencillas, adaptables a los cambios y necesidades específicas. DESARROLLO Debido a la importancia que se le atribuyen a las dietas u otras herramientas actuales y el resultado tanto a nivel nutritivo como a nivel de acondicionamiento físico que están resultando, las y los profesionales consultados reafirmaron la importancia de elaborar un plan de actuación que facilite dicha labor y que aporte más medios para tratar la obesidad. Las pautas que se aportan son aplicables a cualquier usuario con necesidades de regulación de procesos metabólicos nutricionales tal que: sobrepeso, obesidad, diabetes, HTA y para todos los usuarios, realizando así una labor preventiva y no correctiva ni paliativa. Se cubrir la necesidad principal de generar conceptos claros y concisos para proveer un estilo de vida saludable de modo natural y permanente, teniendo en cuenta el no añadir costes inasumibles personales o económicos al usuario. CONCLUSIONES Mediante la revisión bibliográfica y las entrevistas se han observado las recomendaciones desde Atención Primaria en la prevención del sobrepeso y obesidad, y por ello la posibilidad y utilidad de realizar una herramienta para la promoción de salud y de hábitos higiénico-dietéticos. Este documento tiene como finalidad utilizarse como Plan de Actuación dirigido a los profesionales para la prevención del sobrepeso y obesidad, constatando que no existe motivo por el cual no pueda ser dirigido a cualquier usuario y en cualquier etapa de su ciclo vital. Palabras Clave: Hábitos de vida / Prevención Primaria/ Obesidad /Sobrepeso / Promoción de la salud / Pautas / Nutrición / Ejercicio Físico/ Atención Primaria de Salud

Building a molecular PrussianBlueAnalogue FeII/CoIII cube around a Cs+ ion; a preferred, tight, robust, water soluble, and kinetically inert encapsulator

The preparation of a caesium inclusion complex of the molecular cube [{CoIII(Me3-tacn)}4{FeII(CN)6}4]}]4–, a mixed valent molecular Prussian Blue Analogue bearing bridging cyanido ligands, has been achieved by following a redox-triggered self-assembly process in aqueous solution. The assembly has been shown to be Cs-preferred as, even in the presence of Na+ in solution, no Na-encapsulated have been found in the assembled product when Cs+ is present in the reaction medium. Even so, the tightness of the system produces large amounts of a void cubic structure whenever not large excesses of Cs+ are present. The species is robust, extremely soluble in aqueous media, pH-stable in the 1–13 range, and redox inactive between −400 and 600 mV. The molecular species has been characterised by UV–vis, ICP, multinuclear NMR spectroscopy, and electrochemistry. As expected from previous data reported, the complex in aqueous solution is totally inert to cation exchange, the leaching of the encapsulated Cs+ being hampered by the small size of the cube portal

Self‐assembled highly positively charged allyl‐Pd crowns: cavity‐pocket driven interactions of fluoroanions

A series of dodecanuclear highly positively charged homo‐ and heterometallamacrocycles [{Pd(η 3 ‐2‐Me‐C 3 H 4 )} 6 (4‐PPh 2 py) 12 {M 2 (tpbz)} 3 ] 18+ (M = Pd, Pt; tpbz = 1,2,4,5‐tetrakis(diphenylphosphanylbenzene) were synthesized by the quantitative self‐assembly of {Pd(η 3 ‐2‐Me‐C 3 H 4 )} + , {M 2 (tpbz)} 4+ and 4‐PPh 2 py moieties in 2:1:4 molar ratio. The cationic assemblies were obtained as salts of different fluorinated anions that display diverse sizes and electronic properties, namely BF 4 ‐ , PF 6 ‐ , SbF 6 ‐ and CF 3 SO 3 ‐ . The new crown‐like metallamacrocycles showed remarkable differences in their NMR spectra due to the presence of the different counteranions. On the basis of the observed variations, the metallacycles have been tested as catalytic precursors in allylic alkylation reactions. The anion‐dependent activity and selectivity has been analysed and compared with that of the corresponding monometallic allylic corners [Pd(η 3 ‐2‐Me‐C 3 H 4 )(4‐PPh 2 py) 2 ]X (X = BF 4 ‐ , PF 6 ‐ , SbF 6 ‐ , CF 3 SO 3 ‐ ). DFT calculations have been employed in order to help to the interpretation of the experimental data and to model the anion‐crown interactions

Efferocytosis promotes suppressive effects on dendritic cells through prostaglandin E2 production in the context of autoimmunity

Introduction: Efferocytosis is a crucial process by which apoptotic cells are cleared by phagocytes, maintaining immune tolerance to self in the absence of inflammation. Peripheral tolerance, lost in autoimmune processes, may be restored by the administration of autologous dendritic cells loaded with islet apoptotic cells in experimental type 1 diabetes. Objective: To evaluate tolerogenic properties in dendritic cells induced by the clearance of apoptotic islet cells, thus explaining the re-establishment of tolerance in a context of autoimmunity. Methods: Bone marrow derived dendritic cells from non-obese diabetic mice, a model of autoimmune diabetes, were generated and pulsed with islet apoptotic cells. The ability of these cells to induce autologous T cell proliferation and to suppress mature dendritic cell function was assessed, together with cytokine production. Microarray experiments were performed using dendritic cells to identify differentially expressed genes after efferocytosis. Results: Molecular and functional changes in dendritic cells after the capture of apoptotic cells were observed. 1) Impaired ability of dendritic cells to stimulate autologous T cell proliferation after the capture of apoptotic cells even after proinflammatory stimuli, with a cytokine profile typical for immature dendritic cells. 2) Suppressive ability of mature dendritic cell function. 3) Microarray-based gene expression profiling of dendritic cells showed differential expression of genes involved in antigen processing and presentation after efferocytosis. 4) Prostaglandin E2 increased production was responsible for immunosuppressive mechanism of dendritic cells after the capture of apoptotic cells. Conclusions: The tolerogenic behaviour of dendritic cells after islet cells efferocytosis points to a mechanism of silencing potential autoreactive T cells in the microenvironment of autoimmunity. Our results suggest that dendritic cells may be programmed to induce specific immune tolerance using apoptotic cells; this is a viable strategy for a variety of autoimmune diseases.This work was supported by grants from the Fondo de Investigaciones Sanitarias (PS09/00253 and PI12/00195) of the Carlos III Institute of Health, www.isciii.es. RP was supported by the Instituto de Salud Carlos III of the Spanish National Institute of Health (FIS05/00418). MVP is funded by the stabilization program of Miguel Servet biomedical researchers and RMA by the program of research technicians of the Instituto de Salud Carlos III and Direcció d’Estrategia i Coordinacio, Health Dept. of the Catalonian Government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Kineticomechanistic study of the redox pH cycling processes occurring on a robust water-soluble cyanido-bridged mixed-valence {CoIII/FeII}2 square

A kineticomechanistic study of reversible electron-transfer processes undergone by the water-soluble, cyanido-bridged mixed-valence [{CoIII{(Me)2(μ-ET)cyclen}}2{(μ-NC)2FeII(CN)4}2]2- square has been carried out. The oxidation reaction consists of a two-step process with the participation of a solvent-assisted outer-sphere complex, as a result of the establishment of hydrogen bonds that involve the oxo groups of the oxidant (peroxodisulfate) and the terminal cyanido ligands of the tetrametallic square. The formally endergonic reduction reaction of the fully oxidized ([{CoIII{(Me)2(μ-ET)cyclen}}2{(μ-NC)2FeIII(CN)4}2]) core by water, producing hydrogen peroxide from water even at low pH values, is also a two-step process. Each one of these processes requires a set of two preequilibria involving the association of OH- and its subsequent deprotonation by a further OH- anion. The structure of the square compound in its fully protonated form has also been determined by X-ray diffraction and shows the existence of strong hydrogen-bonding interactions, in agreement with the rather high basicity of the terminal cyanido ligands. Likewise, density functional theory calculations on the tetrametallic complex showed zones with negative electrostatic potential around the FeII centers of the square that would account for the establishment of the hydrogen bonds found in the solid state. Spectroelectrochemistry experiments demonstrated the singular stability of the {CoIII/FeII}2 2- complex, as well as that of their partially, {Co2 III/FeIIIFeII}-, and fully, {CoIII/FeIII}2, oxidized counterparts because no hysteresis was observed in these measurements.

Self-assembly and properties of a discrete water-soluble prussian blue analogue FeII/CoIII cube: confinement of a water molecule in aqueous solution

Novel types of water-soluble anionic cubic cages, K4[{CoIII(Me3-Tacn)}4{FeII(CN)6}4] and Na4[{CoIII(Me3-Tacn)}4{FeII(CN)6}4] (Me3-Tacn = 1,4,7-trimethyl-1,4,7-triazacyclononane), were prepared by means of a mechanistically designed self-assembly process between [Co(Me3-Tacn)Cl3] and A4[FeII(CN)6] (M = Na or K), consisting of a rate-limiting outer-sphere redox step, followed by a fast substitution/inner-sphere redox reaction sequence. These compounds show remarkable stability in aqueous solution at different pH ranges, displaying neat protonation processes and reversible oxidation with peroxodisulfate to its neutral {FeIII4CoIII4} form. Furthermore, the cages behave as a robust and water-soluble molecular Prussian Blue analogue capable of encapsulating {Na-OH2}+ pairs and K+ cations in aqueous solution, with the cubic structure of the complex being preserved. Substitution of the {Na-OH2}+ pairs by K+ is easily accomplished, and the electrochemical properties of the sodium and potassium salts of the new cages have been found to be dramatically dependent on the encapsulated units

Amino acids with fluorescent tetrazine ethers as bioorthogonal handles for peptide modification

A set of 3-bromo-1,2,4,5-tetrazines with three distinct substitutions have been used as reagents for late-stage functionalization of small molecules through nucleophilic aromatic substitution. Spectroscopic studies of the products obtained proved that tetrazine ethers are intrinsically fluorescent. This fluorescence is lost upon inverse Electron-Demand Diels-Alder (iEDDA) cycloaddition with strained alkenes. Tetrazine-phenol ethers are rather interesting because they can undergo rapid iEDDA reactions with a second order rate constant (k2) compatible with bioorthogonal ligations. As a showcase, L-tyrosine was derivatized with 3-bromo-6-methyl-1,2,4,5-tetrazine and coupled to the peptide drug octreotide. This peptide was detected in cellular flow cytometry, and its fluorescence turned off through a bioorthogonal iEDDA cycloaddition with a strained alkene, showing for the first time the detection and reactivity of intrinsically fluorescent tetrazines in a biologically relevant context. The synthesis and characterization of fluorescent tetrazine ethers with bioorthogonal applicability pave the way for the generation of useful compounds for both detection and bioconjugation in vivo

Kineticomechanistic study of the redox pH cycling processes occurring on a robust water-soluble cyanido-bridged mixed-valence {CoIII/FeII}2 square

A kineticomechanistic study of reversible electron-transfer processes undergone by the water-soluble, cyanido-bridged mixed-valence [{Co{(Me)(μ-ET)cyclen}}{(μ-NC)Fe(CN)}] square has been carried out. The oxidation reaction consists of a two-step process with the participation of a solvent-assisted outer-sphere complex, as a result of the establishment of hydrogen bonds that involve the oxo groups of the oxidant (peroxodisulfate) and the terminal cyanido ligands of the tetrametallic square. The formally endergonic reduction reaction of the fully oxidized ([{Co{(Me)(μ-ET)cyclen}}{(μ-NC)Fe(CN)}]) core by water, producing hydrogen peroxide from water even at low pH values, is also a two-step process. Each one of these processes requires a set of two preequilibria involving the association of OH and its subsequent deprotonation by a further OH anion. The structure of the square compound in its fully protonated form has also been determined by X-ray diffraction and shows the existence of strong hydrogen-bonding interactions, in agreement with the rather high basicity of the terminal cyanido ligands. Likewise, density functional theory calculations on the tetrametallic complex showed zones with negative electrostatic potential around the Fe centers of the square that would account for the establishment of the hydrogen bonds found in the solid state. Spectroelectrochemistry experiments demonstrated the singular stability of the {Co/Fe} complex, as well as that of their partially, {Co/FeFe}, and fully, {Co/Fe}, oxidized counterparts because no hysteresis was observed in these measurements

Molecular Approach to Alkali-Metal Encapsulation by a Prussian Blue Analogue FeII/CoIII Cube in Aqueous Solution: A Kineticomechanistic Exchange Study

The preparation of a series of alkali-metal inclusion complexes of the molecular cube [{CoIII(Me3-tacn)}4{FeII(CN)6}4]4- (Me3-tacn = 1,4,7-trimethyl-1,4,7-triazacyclononane), a mixed-valent Prussian Blue analogue bearing bridging cyanido ligands, has been achieved by following a redox-triggered self-assembly process. The molecular cubes are extremely robust and soluble in aqueous media ranging from 5 M [H+] to 2 M [OH-]. All the complexes have been characterized by the standard mass spectometry, UV-vis, inductively coupled plasma, multinuclear NMR spectroscopy, and electrochemistry. Furthermore, X-ray diffraction analysis of the sodium and lithium salts has also been achieved, and the inclusion of moieties of the form {M-OH2}+ (M = Li, Na) is confirmed. These inclusion complexes in aqueous solution are rather inert to cation exchange and are characterized by a significant decrease in acidity of the confined water molecule due to hydrogen bonding inside the cubic cage. Exchange of the encapsulated cationic {M-OH2}+ or M+ units by other alkali metals has also been studied from a kineticomechanistic perspective at different concentrations, temperatures, ionic strengths, and pressures. In all cases, the thermal and pressure activation parameters obtained agree with a process that is dominated by differences in hydration of the cations entering and exiting the cage, although the size of the portal enabling the exchange also plays a determinant role, thus not allowing the large Cs+ cation to enter. All the exchange substitutions studied follow a thermodynamic sequence that relates with the size and polarizing capability of the different alkali cations; even so, the process can be reversed, allowing the entry of {Li-OH2}+ units upon adsorption of the cube on an anion exchange resin and subsequent washing with a Li+ solution