Selective oxidation of alkyl and aryl glyceryl monoethers catalysed by an engineered and immobilised glycerol dehydrogenase

Enzymes acting over glyceryl ethers are scarce in living cells, and consequently biocatalytic transformations of these molecules are rare despite their interest for industrial chemistry. In this work, we have engineered and immobilised a glycerol dehydrogenase from Bacillus stearothermophilus (BsGlyDH) to accept a battery of alkyl/aryl glyceryl monoethers and catalyse their enantioselective oxidation to yield the corresponding 3-alkoxy/aryloxy-1-hydroxyacetones. QM/MM computational studies decipher the key role of D123 in the oxidation catalytic mechanism, and reveal that this enzyme is highly enantioselective towards S-isomers (ee > 99%). Through structure-guided site-selective mutagenesis, we find that the mutation L252A sculpts the active site to accommodate a productive configuration of 3-monoalkyl glycerols. This mutation enhances the kcat 163-fold towards 3-ethoxypropan-1, 2-diol, resulting in a specific activity similar to the one found for the wild-type towards glycerol. Furthermore, we immobilised the L252A variant to intensify the process, demonstrating the reusability and increasing the operational stability of the resulting heterogeneous biocatalyst. Finally, we manage to integrate this immobilised enzyme into a one-pot chemoenzymatic process to convert glycidol and ethanol into 3-ethoxy-1-hydroxyacetone and (R)-3-ethoxypropan-1, 2-diol, without affecting the oxidation activity. These results thus expand the uses of engineered glycerol dehydrogenases in applied biocatalysis for the kinetic resolution of glycerol ethers and the manufacturing of substituted hydroxyacetones. This journal i

Unveiling the mechanism of hydrotropy : evidence for water-mediated aggregations of hydrotrope around the solute

A recent proposal attributes the origin of hydrotropy to the water-mediated aggregation of hydrotrope molecules around the solute. Experimental evidence for this phenomenon is reported for the first time in this work, using 1H-NMR. A new computational technique to quantify apolarity is introduced and is used to show that apolarity of both solute and hydrotrope is the driving force of hydrotropy.This work was developed within the scope of the projects CICECO-Aveiro Institute of Materials, UIDB/50011/2020 & UIDP/50011/2020, and CIMO-Mountain Research Center, UIDB/00690/2020, both financed by national funds through the FCT/MEC and when appropriate co-financed by FEDER under the PT2020 Partnership Agreement. The NMR 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). Financial support from Ministerio de Ciencia, Innovación (project RTI2018-093431-B-I00) and the Gobierno de Aragón (Group E37_17R) co-funded by FEDER 2014-2020 “Construyendo Europa desde Aragón” is acknowledged. B. P. S. acknowledges FCT for her PhD grant SFRH/BD/138439/2018.Peer reviewe

Glycerol ethers as hydrotropes and their use to enhance the solubility of phenolic acids in water

The use of glycerol ethers (with alkyl side chain ranging from one to six methyl groups) as hydrotropes to enhance the solubility of gallic and syringic acids in water was here studied. These compounds were selected by their intrinsic interest and for serving as models for lignin fractions. The results obtained were compared against traditional co-solvents, demonstrating the exceptional hydrotropic ability of glycerol ethers. Setschenow constants show that the hydrophobicities of both solute and hydrotrope play an important role in the solubility enhancement by hydrotropy, shedding light into its molecular mechanism

Dietary α‐Linolenic Acid, Marine ω‐3 Fatty Acids, and Mortality in a Population With High Fish Consumption: Findings From the PREvención con DIeta MEDiterránea (PREDIMED) Study

Background: Epidemiological evidence suggests a cardioprotective role of α‐linolenic acid (ALA), a plant‐derived ω‐3 fatty acid. It is unclear whether ALA is beneficial in a background of high marine ω‐3 fatty acids (long‐chain n‐3 polyunsaturated fatty acids) intake. In persons at high cardiovascular risk from Spain, a country in which fish consumption is customarily high, we investigated whether meeting the International Society for the Study of Fatty Acids and Lipids recommendation for dietary ALA (0.7% of total energy) at baseline was related to all‐cause and cardiovascular disease mortality. We also examined the effect of meeting the society's recommendation for long‐chain n‐3 polyunsaturated fatty acids (≥500 mg/day). Methods and Results: We longitudinally evaluated 7202 participants in the PREvención con DIeta MEDiterránea (PREDIMED) trial. Multivariable‐adjusted Cox regression models were fitted to estimate hazard ratios. ALA intake correlated to walnut consumption (r=0.94). During a 5.9‐y follow‐up, 431 deaths occurred (104 cardiovascular disease, 55 coronary heart disease, 32 sudden cardiac death, 25 stroke). The hazard ratios for meeting ALA recommendation (n=1615, 22.4%) were 0.72 (95% CI 0.56–0.92) for all‐cause mortality and 0.95 (95% CI 0.58–1.57) for fatal cardiovascular disease. The hazard ratios for meeting the recommendation for long‐chain n‐3 polyunsaturated fatty acids (n=5452, 75.7%) were 0.84 (95% CI 0.67–1.05) for all‐cause mortality, 0.61 (95% CI 0.39–0.96) for fatal cardiovascular disease, 0.54 (95% CI 0.29–0.99) for fatal coronary heart disease, and 0.49 (95% CI 0.22–1.01) for sudden cardiac death. The highest reduction in all‐cause mortality occurred in participants meeting both recommendations (hazard ratio 0.63 [95% CI 0.45–0.87]). Conclusions: In participants without prior cardiovascular disease and high fish consumption, dietary ALA, supplied mainly by walnuts and olive oil, relates inversely to all‐cause mortality, whereas protection from cardiac mortality is limited to fish‐derived long‐chain n‐3 polyunsaturated fatty acids. Clinical Trial Registration URL: http://www.Controlled-trials.com/. Unique identifier: ISRCTN35739639

Steps forward toward the substitution of conventional solvents in the Heck–Mizoroki coupling reaction: Glycerol-derived ethers and deep eutectic solvents as reaction media

Dedicated to the memory of Prof. José Ignacio Garcı́a Laureiro (1959−2019).Glycerol-derived ethers and their eutectic mixtures with two renewable ammonium salts (ChCl and N00Cl) are effectively used as new green solvents for the immobilization of PVP-Palladium nanoparticles. Those air-stable, selective, and recoverable catalytic systems are applied in the benchmark Heck–Mizoroki coupling reaction between iodobenzene and n-butyl acrylate in order to evaluate the influence of the different solvation properties of the solvent on the reaction results. The HBD ability (α acidity) of the solvent seems to play a crucial role in the reaction selectivity.The authors acknowledge the financial support from the Ministerio de Ciencia, Innovación y Universidades (Project RTI2018-093431-B-I00), the Gobierno de Aragón (E37 20R), and the European Regional Development Funds. A. Leal-Duaso thanks the MECD for a FPU grant (FPU14/04338).Peer reviewe

Steps Forward toward the Substitution of Conventional Solvents in the HeckMizoroki Coupling Reaction: Glycerol-Derived Ethers and Deep Eutectic Solvents as Reaction Media

Dedicated to the memory of Prof. José Ignacio Garcı́a Laureiro (1959−2019).Glycerol-derived ethers and their eutectic mixtures with two renewable ammonium salts (ChCl and N00Cl) are effectively used as new green solvents for the immobilization of PVP-Palladium nanoparticles. Those air-stable, selective, and recoverable catalytic systems are applied in the benchmark Heck–Mizoroki coupling reaction between iodobenzene and n-butyl acrylate in order to evaluate the influence of the different solvation properties of the solvent on the reaction results. The HBD ability (α acidity) of the solvent seems to play a crucial role in the reaction selectivity.The authors acknowledge the financial support from the Ministerio de Ciencia, Innovación y Universidades (Project RTI2018-093431-B-I00), the Gobierno de Aragón (E37 20R), and the European Regional Development Funds. A. Leal-Duaso thanks the MECD for a FPU grant (FPU14/04338).Peer reviewe

An extremely highly recoverable clay-supported Pd nanoparticle catalyst for solvent-free Heck-Mizoroki reactions

Palladium nanoparticles supported on LAPONITE®, a synthetic clay, are shown to constitute a highly robust and stable catalytic system for Heck–Mizoroki reactions carried out under solventless conditions. Both the preparation and the use of the catalyst are straightforward, allowing easy separation of the reaction products in pure form. In the case of the reaction between butyl acrylate and iodobenzene, up to 50 catalyst cycles can be performed before observing a noticeable decrease in activity. After reactivation of the catalyst by calcination, it can be further used for at least an additional 25 reactions. The stability of the catalyst seems to be related to the electronic density of the reacting alkene, as illustrated by the results obtained using the same catalyst with other alkenes

Microwave-promoted solventless Mizoroki-Heck reactions catalysed by Pd nanoparticles supported on laponite clay

A new family of solid catalysts has been prepared by supporting palladium nanoparticles on a synthetic clay (laponite) using a straightforward and robust procedure. These solids have been used as catalysts in a Mizoroki-Heck reaction, in solventless conditions, activated by microwave radiation. Complete conversions and high product yields can be obtained in a few minutes, and the catalyst can be efficiently recovered by extracting reaction products in essentially pure form. In the best cases, catalysts can be used up to thirteen times with good results.Financial support from the Spanish MINECO (project CTQ2011-28124-C02-01), the European Social Fund (ESF) and the Gobierno de Aragón (Grupo Consolidado E11) is gratefully acknowledged.Peer Reviewe

Proceso tándem ácido/base para la síntesis de éteres no simétricos derivados de glicerol: optimización y escalado

Póster presentado a la Reunión Bienal de la Sociedad Española de Catálisis (SECAT): Nuevos retos de la catálisis en química, medio ambiente y energía, celebrada en Valencia del 18 al 20 de octubre de 2021.Ministerio de Ciencia, Innovación y Universidades (proyecto RTI2018-093431-B-100) y Gobierno de Aragón (grupo E37_20R cofinanciado con FEDER 2014-2020 "Construyendo Europa desde Aragón").Peer reviewe

Diseño de catalizadores basados en NPs de Pd soportadas, para reacciones de interés sintético

Trabajo presentado a la 6ª Jornada de Jóvenes Investigadores en Física y Química de Aragón celebrada en Zaragoza el 20 de noviembre de 2014.En la última década la comunidad científica internacional ha hecho un esfuerzo notable por reducir el impacto medioambiental de los procesos químicos. En este contexto se ha hecho especial hincapié en el diseño de catalizadores más activos y recuperables, que permitan reducir el coste energético y optimizar la selectividad los procesos químicos, de modo que se optimice el uso de materias primas y se disminuya la producción de residuos. El objetivo de nuestra línea de investigación es el diseño de catalizadores heterogéneos que disminuyan el impacto medioambiental de procesos químicos de interés sintético. En esta comunicación presentamos un novedoso sistema catalítico, basado en nanopartículas de Pd soportadas en laponita. Este sistema es fácil de preparar y de manipular, y ha sido optimizado para reacciones de acoplamiento C–C, reacciones de hidrogenación, así como procesos tándem acoplamiento Heck + hidrogenación. Todos los procesos se han llevado a cabo en ausencia de disolvente y empleando una gran variedad de sustratos olefínicos. Además se ha recuperado el catalizador, de forma sencilla, y se ha reutilizado en un gran número de ocasiones (hasta 50 para reacciones de acoplamiento), sin pérdida de actividad catalítica.Peer reviewe