Experimental Study of the Mechanism of the Pd-catalyzed Aryl-alkyl Negishi Coupling using Hybrid Phosphine- Electron Withdrawing Olefin Ligands

Producción CientíficaA detailed study of the Negishi cross-coupling reaction of ArI (Ar = 2-C6H4CO2Et) and ZnEt2 with palladium catalysts containing conventional phosphines versus one using a chelating hybrid phosphine–electron-withdrawing olefin (P-EWO) ligand reveals that for conventional phosphines (e.g., PPh3) β-H elimination from intermediate [PdArEt(PPh3)2] is competitive with Ar–Et reductive elimination and is responsible for part of the undesired reduction product ArH. In contrast, with the EWO phosphine, the β-H elimination from intermediate [PdArEt(P-EWO)] is slow compared to the fast Ar–Et reductive elimination, and the undesired reduction product ArH observed proceeds in this case of hydrolysis of ZnArEt, formed in transmetalations where Ar is transferred from Pd to Zn. The rate of these transmetalations is comparable to the rate of reductive eliminations. Consequently, undesired transmetalations affording [PdEt2(P-EWO)] and ZnArEt are more effective at early stages of the reactions and less effective when the ethylating agent becomes poorer in ZnEt2 and richer in ZnEtX (X = I), as the reaction proceeds. Careful analysis of the experiments reveals the detailed changing evolution of the reaction, not only providing the main features of the catalytic cycle but also deducing how the reagents in the system change with time and what the effects on the products of these changes are.Junta de Castilla y León (programa de apoyo a proyectos de investigación – Ref. GR169 and VA256U13)Ministerio de Economía, Industria y Competitividad (CTQ2013-48406-P

Efficient gene transfer by transferrin lipoplexes in the presence of serum

Cationic lipids are being used increasingly as reagents for gene delivery both in vitro and in vivo. One of the limitations to the application of cationic lipid-DNA complexes (lipoplexes) in vivo is the inhibition of gene delivery by serum. In this study, we have shown that transferrin (Tf)-lipoplexes, which had transferrin adsorbed at their surface via electrostatic interactions, are much more effective than plain lipoplexes in transfecting cells in the presence of relatively high concentrations (up to 60%) of fetal bovine serum (FBS). Serum even enhanced transfection by Tf-lipoplexes composed of 1,2-dioleoyl-3-(trimethylammonium) propane (DOTAP)/dioleoylphosphatidylethanolamine (DOPE)/pCMVLacZ at high lipid/DNA (+/-) charge ratios, and inhibited lipofection for those with low charge ratios when they were added to the cells immediately after the preparation of complexes. The effect of serum on lipofection was dose-dependent. Preincubation of the complexes at 20°C for 6 h led to serum resistance, even for the negatively charged transferrin-lipoplexes. A similar tendency was observed for DOTAP/cholesterol and DOTAP/DOPE/cholesterol liposomes. The percentage of cells transfected, measured by β-galactosidase expression, also increased with the serum concentration. Cell viability was not affected significantly when the cells were incubated with the complexes for 4 h at 37°C, followed by a 48-h incubation. Our findings extend the scope of previous studies where transferrin-lipoplexes were used to introduce DNA into cells, rendering these complexes and their future derivatives potential alternatives to viral vectors for gene delivery in vivo. Copyright (C) 2000 Elsevier Science B.V

Códigos correctores óptimos mediante técnicas elementales

Los códigos correctores de errores se utilizan cuando se quiere enviar una información a través de un canal sujeto a ruido. Un código corrector añade información extra al mensaje que se quiere transmitir con el fin de recuperar la información enviada. En este trabajo se tratan los códigos en bloque y en concreto los códigos lineales. Se presentan diferentes métodos sencillos para la obtención de códigos lineales óptimos y se estudia el código simplex ternario y el código Reed Muller ternario.Grado en Matemática

Ranking Ligands by Their Ability to Ease (C6F5)2NiIIL → Ni0L + (C6F5)2 Coupling versus Hydrolysis: Outstanding Activity of PEWO Ligands

Producción CientíficaThe NiII literature complex cis-[Ni(C6F5)2(THF)2] is a synthon of cis-Ni(C6F5)2 that allows us to establish a protocol to measure and compare the ligand effect on the NiII → Ni0 reductive elimination step (coupling), often critical in catalytic processes. Several ligands of different types were submitted to this Ni-meter comparison: bipyridines, chelating diphosphines, monodentate phosphines, PR2(biaryl) phosphines, and PEWO ligands (phosphines with one potentially chelate electron-withdrawing olefin). Extremely different C6F5–C6F5 coupling rates, ranging from totally inactive (producing stable complexes at room temperature) to those inducing almost instantaneous coupling at 25 °C, were found for the different ligands tested. The PR2(biaryl) ligands, very efficient for coupling in Pd, are slow and inefficient in Ni, and the reason for this difference is examined. In contrast, PEWO type ligands are amazingly efficient and provide the lowest coupling barriers ever observed for NiII complexes; they yield up to 96% C6F5–C6F5 coupling in 5 min at 25 °C (the rest is C6F5H) and 100% coupling with no hydrolysis in 8 h at −22 to −53 °C.Ministerio de Economía, Industria y Competitividad (Projects CTQ2017-89217-P and CTQ2016-80913-P)Junta de Castilla y León (projects VA051P17 and VA062G18)Ministerio de Economía, Industria y Competitividad FPI scholarship (BES-2017-080726

Sugar-based bicyclic monomers for aliphatic polyesters: a comparative appraisal of acetalized alditols and isosorbide

Three series of polyalkanoates (adipates, suberates and sebacates) were synthesized using as monomers three sugar-based bicyclic diols derived from D-glucose (Glux-diol and isosorbide) and D-mannose (Manx-diol). Polycondensations were conducted in the melt applying similar reaction conditions for all cases. The aim was to compare the three bicyclic diols regarding their suitability to render aliphatic polyesters with enhanced thermal and mechanical properties. The ensuing polyesters had molecular weights (Mw) in the 25,000–50,000 g mol-1 range with highest values being attained for Glux-diol. All the polyesters started to decompose above 300 °C and most of them did not display perceivable crystallinity. On the contrary, they had glass transition temperatures much higher than usually found in homologous polyesters made of alkanediols, and showed a stress– strain behavior consistent with their Tg values. Glux-diol was particularly effective in increasing the Tg and to render therefore polyesters with high elastic modulus and considerable mechanical strength.Peer ReviewedPostprint (published version

The stille reaction, 38 years later

Producción CientíficaThe first now named Stille reaction was published 38 years ago, and the last comprehensive revision of this catalysis was in 2004. Since then the knowledge of the different steps of the three possible (and sometimes competing) reaction pathways (cyclic, open, and ionic) has been almost completed by synergistic experimental and theoretical studies: the Stille reaction is perhaps the best characterized catalytic process if we consider the number of intermediates that have been detected. This review concentrates on the mechanistic new knowledge, and on important aspects as the revolution with the use of bulky phosphines, the bimetallic alternative of the Stille reaction, the enantioselectivity in Stille and palladium free Stille processes, the meaning of copper effect, or the possible approaches to make Stille coupling a greener process.Junta de Castilla y León (programa de apoyo a proyectos de investigación – Ref. GR 169 and VA256U13)Ministerio de Economía, Industria y Competitividad (CTQ2013-48406-P

Na-ion battery development: from electrode processing studies to heat generation model of a monolayer pouch cell

369 p.Entre la variedad de sistemas de almacenamiento de energía, la inclusión de baterías en las redes eléctricas balancearía el equilibrio del suministro y la demanda de electricidad. Por ejemplo, la tecnología de iones de sodio podría ser una opción viable para una próxima generación de baterías para aplicaciones estacionarias, debido a diversos aspectos, como su potencial para alcanzar un coste global menor debido a la abundancia y distribución geográfica de las fuentes de sodio en comparación con las de litio. Además, su fabricación sigue las pautas técnicas y de procesado de la tecnología de iones de litio actualmente implementados a escala industrial y, por lo tanto, su escalado sería más fácil y sin inversiones significativas en comparación otro tipo de tecnologías más novedosas. Sin embargo, el desarrollo de baterías de iones de sodio presenta aun desafíos críticos que deben superarse. Es por ello necesario impulsar la investigación en los procesos de escalado, procesado de electrodos y diseño de celdas paraaproximar esta tecnología a los requerimientos de una tecnología madura. Esta tesis doctoral incluye el trabajo realizado en el desarrollo de una batería con tecnología Na-ion. Es un trabajo diferenciado del estado del arte de este tipo de tecnología, y centrado en una perspectiva ingenieril de su desarrollo, empezando desde la fabricación de celdas de botón y acabando con el desarrollo de una celda de tipo pouch-cell de iones de sodio monocapa. Este trabajo representa un informe completo de la mencionada tecnología en términos de procesado de electrodos, estrategias encaminadas a superar las limitaciones de esta tecnología y fabricación de una celda completa con sus respectivas caracterizaciones electroquímicas y térmicas

Highly enantioselective addition of dimethylzinc to fluorinated alkyl ketones, and the mechanism behind it

Producción CientíficaChiral-diamine catalyzed addition of ZnMe2 to PhC(O)CF2X (in dichloromethane at −30 °C) affords fluorinated alkyl tertiary alcohols in high yield (quantitative for X = H, F, Cl; 84% for X = CF3) and up to 99% ee. These conditions are similarly very efficient for other various ArC(O)CF3 molecules. A fine analysis of the results can be performed based on a double-cycle mechanism.Ministerio de Economía, Industria y Competitividad (Projects CTQ-2016-80913-P and CTQ2014-52796)Junta de Castilla y León (programa de apoyo a proyectos de investigación - Ref. VA051P17

Triblock copolyesters derived from lactic acid and glucose: synthesis, nanoparticle formation and simulation

ABA triblock copolyesters were synthesized by ring-opening polymerization (ROP) of l-lactide in solution initiated by a telechelic d-glucose-based polyester macroinitiator. The macroinitiator with a number-average molecular weight about 2500 g mol-1 was synthesized by non-stoichiometric polycondensation in the melt of 2,4:3,5-di-O-methylene-d-glucitol and dimethyl succinate. Two triblock copolyesters of Mn ranging between ~6000 and ~9000 g mol-1, and differing in the length of the polylactide blocks were prepared. These copolyesters started to decompose when heated at ~220 °C and degraded slowly upon aqueous incubation under physiological conditions. They did not display any perceivable crystallinity and showed a single glass transition temperature (Tg) around 60 °C with the higher value corresponding to the larger content in glucitol units. The copolyesters were able to form nanoparticles with average diameters of ~100–130 nm and satisfactory dispersity. The effect of the block lengths on size, ¿-potential values and physical stability of the nanoparticles was evaluated. A molecular dynamics simulation study allowed modelling the two-phase structure of the nanoparticles and evidenced the preference of the glucose-based block to be peripherally located.Peer ReviewedPostprint (author's final draft

Fully bio-based aromatic–aliphatic copolyesters: poly(butylene furandicarboxylate-co-succinate)s obtained by ring opening polymerization

Poly(butylene 2,5-furandicarboxylate-co-succinate) copolyesters (coPBFxSy) have been synthesized by ring opening polymerization (ROP). Cyclic butylene 2,5-furandicarboxylate and butylene succinate oligomer mixtures, to be used as monomers for ROP, were prepared by high dilution condensation and enzymatic cyclization reactions, respectively. Two different catalytic systems, tin dioctanoate and supported Candida antarctica lipase B (CALB), were used for polymerization. Thus two series of copolyesters covering the whole range of compositions were prepared and their properties comparatively examined. In both cases, random copolyesters with compositions close to those used in their respective feeds were obtained. The influence of composition on reaction kinetics with respect to time and temperature was evaluated for the two series. Chemically catalyzed ROP rendered copolyesters with Mw in the ~50 000–65 000 g mol-1 range, whereas values between 15 000 and 45 000 g mol-1 were attained when the ROP reaction was assisted by CALB. The thermal behavior of coPBFxSy obtained by ROP was similar to that reported for such copolymers prepared by melt polycondensation. They all start to decompose above 300 °C and display melting enthalpy and temperatures that decrease with copolymerization, attaining minimum values when the comonomer contents are approximate to balance. On the contrary, the glass-transition temperature increased almost linearly with the content of butylene furandicarboxylate units, covering the whole range of values between those of the two parent homopolyesters. Small deviations in thermal properties observed between the two series could be attributed to their differences in molecular weights. Hydrolytic and enzymatic degradation studies revealed that coPBFxSy became more degradable with increasing content of succinic units, whereas the homopolyester PBF remained practically unaffected when incubated under similar conditions.Peer ReviewedPostprint (author's final draft