Mesoporous multifunctional nanomaterials SBA-15 and MCM-41 type applied to fine chemical processes

Los artículos que componen la presente Memoria de Tesis Doctoral forman parte de las principales líneas de investigación actualmente en desarrollo en el Grupo de Investigación FQM-383, Nanoquímica y Valorización de Biomasa y Residuos (NANOVAL), asumiendo como objetivos fundamentales el uso de materiales eficientes y procesos más selectivos para la implementación procesos sostenibles en la industria química, farmacéutica, etc. En esta Memoria de Tesis Doctoral, se expone el potencial que presentan los materiales mesoporosos en el ámbito de catálisis heterogénea, permitiendo ser funcionalizados por síntesis directa o mediante procesos post-sintéticos. La funcionalización de los materiales mesoporosos ha permitido el uso de éstos como catalizadores en diferentes reacciones químicas de interés industrial. En el primer trabajo descrito en la memoria (Capítulo III.1), titulado “Continuous flow synthesis of supported magnetic iron oxide nanoparticles for efficient isoeugenol conversion to vanillin”, se ha procedido a la síntesis de nuevos catalizadores magnéticos, incorporando nanopartículas de hierro sobre un soporte mesoporoso (Al-SBA-15) utilizando un sistema de flujo continuo, en un único paso “one pot”. El proceso en flujo continuo nos ha permitido obtener nanocatalizadores magnéticos gracias al paso de una disolución etanólica de la sal de hierro precursora que se hace fluir a través de un reactor en el cual se encuentra empaquetado el material mesoporoso empleado como soporte a una temperatura controlada. Dicho procedimiento es por tanto simple, innovador y eficiente, permitiéndonos investigar la influencia de la velocidad de flujo de la disolución que contiene el precursor metálico y la temperatura de síntesis de los materiales. Los valores de susceptibilidad magnética mostrados por los nanocatalizadores están en el intervalo de 70 a 210 10-6 m3 K g-1, hecho consistente con el contenido de maghemita en el soporte, ya que las nanopartículas de maghemita pura generalmente muestran susceptibilidades magnéticas de aproximadamente 500 10-6 m3 K g-1. Dichos valores de susceptibilidad son suficientemente elevados para que estos materiales sean separables magnéticamente de la mezcla de reacción utilizando un simple imán. La utilización de estos materiales magnéticos en procesos catalíticos ha sido prometedora, en particular, para la reacción de conversión del isoeugenol a vainillina, mostrando una alta actividad catalítica, selectividad y estabilidad química, así como la ventaja de una fácil separación, eliminando la necesidad de procedimientos poco prácticos para el reciclado de los catalizadores. En el trabajo “Mechanochemically synthesized supported magnetic Fe-nanoparticles as catalysts for efficient vanillin production” (Capítulo III.2), se ha estudiado la preparación de materiales magnéticos mediante molienda mecanoquímica empleando como soporte el material mesoporoso Al-SBA-15, un material orgánico de desecho como activador de la fase magnética y una sal precursora de hierro para generar la funcionalidad en el material (fase activa-magnetismo). Además, en el trabajo se optimiza el proceso de síntesis de los nanomateriales, empleando distintas sales precursoras de nanopartículas de hierro (citrato amónico de hierro, nitrato de hierro, perclorato de hierro y cloruro de hierro), diferentes temperaturas de calcinación (300, 400 y 500 ºC) e incorporando en el soporte diferentes contenidos en peso de hierro. De todos los materiales obtenidos a lo largo de dichas investigaciones, solo aquellos preparados con citrato amónico de hierro y nitrato de hierro han mostrado propiedades magnéticas, siendo los materiales con mayor magnetismo los calcinados a una temperatura de 400 ºC. Los materiales han sido caracterizados mediante distintas técnicas como son la adsorción/desorción de N2, difracción de rayos-X (XRD), espectroscopía fotoelectrónica de rayos-X (XPS), microscopía electrónica de barrido acoplada a análisis elemental (SEM-EDX), microscopía electrónica de transmisión (TEM) y susceptibilidad magnética. Los nanocatalizadores magnéticos han demostrado una elevada actividad catalítica y estabilidad química, destacando su capacidad de separación/reusabilidad en las reacciones de oxidación selectivas del isoeugenol (ruptura oxidativa) y del alcohol vainillínico (oxidación) a vainillina. El origen de sus propiedades catalíticas se ha relacionado con la concentración superficial de nanopartículas de hierro y con la interacción Al-Fe. Por último, el estudio de la reutilización de estos nanocatalizadores ha demostrado la estabilidad de estos sistemas bajo las condiciones de reacción de investigadas, exhibiendo actividades catalíticas similares tras cinco usos. Finalmente, en el trabajo “Post-synthetic mechanochemical incorporation of Al species into the framework of porous materials: towards more sustainable redox chemistries” (Capítulo III.3) se han sintetizado diferentes nanomateriales incorporando, mediante molienda mecanoquímica e impregnación, especies de aluminio en proporciones muy bajas (0,2-0,4% en peso) en materiales de sílice mesoporos (SBA-15 y MCM-41). Concretamente, la incorporación del aluminio se ha llevado a cabo utilizando como precursores isopropóxido de aluminio y, por primera vez, materiales MOFs conteniendo Al. Las propiedades físico-químicas de los materiales sintetizados se han caracterizado mediante técnicas como la difracción de rayos-X (XRD), adsorción-desorción de N2, microscopía electrónica de barrido acoplada a análisis elemental (SEM-EDX), espectrometría de masas acoplada a plasma de acoplamiento inducido (ICP/MS), cromatografía de pulsos utilizando piridina y dimetilpiridina como bases valorantes, resonancia magnética nuclear (NMR) y susceptibilidad magnética. Los resultados obtenidos mediante RMN-MAS del Al27 nos indican que la técnica mecanoquímica ha sido capaz de introducir especies de aluminio estructural (Al tetraédrico) en los silicatos SBA-15 y MCM-41 con contenidos de Al muy bajos, siendo la primera vez que se publica dicha incorporación de tipo post-sintético mediante el procedimiento mecanoquímico. A pesar de los contenidos extremadamente bajos en Al (0,2-0,4% en peso) las especies aisladas de óxido de aluminio muestran actividades catalíticas prometedoras en reacciones de oxidación selectiva, utilizando condiciones de reacción suaves (irradiación asistida mediante microondas y molienda mecanoquímica), que incluyen las reacciones de oxidación de alcohol bencílico a benzaldehído, isoeugenol a vainillina y sulfuro de difenilo a sulfóxido de difenilo.The scientific contributions in the present Doctoral Thesis have principal research objectives related to the platform technologies from our research Group FQM-383, Nanochemistry and biomass valorisation and waste (NANOVAL), assuming as fundamental objectives the benign-bydesign preparation of advanced materials for more selective processes to be potentially implemented into more sustainable processes in the chemical, pharmaceutical and related industries. Research studies from the Doctoral Thesis illustrate the potential of mesoporous materials in the field of heterogeneous catalysis, with promising possibilities for their functionalization by direct synthesis or post-synthetic processes. The functionalization of mesoporous materials allowed their use as catalysts in a wide range of reactions such as those catalysed by acid and redox sites and/or biomass conversion processes. In the first work described in the manuscript (chapter III.1) entitled "Continuous flow synthesis of supported magnetic iron oxide nanoparticles for efficient isoeugenol conversion to vanillin", the synthesis of new magnetic catalysts was successfully accomplished, incorporating iron oxide nanoparticles on a mesoporous aluminosilicate support (Al-SBA-15) using a continuous flow system in a single step "one pot" reaction. The continuous flow process allowed us to obtain magnetic nanocatalysts in a simple system by pumping an ethanolic solution containing the dissolved iron salt precursor through a reactor in which the mesoporous material used as support at a controlled temperature is placed in a fixed bed reactor. The synthetic procedure is therefore simple, innovative and efficient, allowing us to investigate the influence of the flow rate of the solution containing the metallic precursor and the synthesis temperature. The values of magnetic susceptibility shown by the nanocatalysts oscillate in the range from 70 to 210 10-6 m3 K g-1, consistent with the maghemite content in the support, due to the fact that pure maghemite has susceptibility values of ca. 500 10-6 m3 K g-1. These susceptibility values endow nanocatalysts with iron oxide nanoparticles with magnetic separation features for a simple nanomaterials recovery from the reaction mixture. The use of magnetic materials in the catalytic process has been promising, especially, in the conversion reaction of isoeugenol to vanillin, where high catalytic activity and stability were observed together with the advantage of simple separation, eliminating the need for impractical procedures for catalysts recycling. The manuscript “Mechanochemically synthesized supported magnetic Fe-nanoparticles as catalysts for efficient vanillin production” (Chapter III.2) proposes a simple and innovative mechanochemical methodology for the preparation of magnetic materials using Al-SBA-15 as mesoporous material support, a waste-derived organic material as an activator of the magnetic phase and iron precursors as the active phase (iron oxide nanoparticles) in the material. Practically, the nanomaterials synthesis was optimised using different iron precursor salts (ammonium iron (III) citrate, Iron (III) nitrate, Iron (III) perchlorate hydrate and iron (III) chloride), different calcination temperatures (300, 400 y 500 ºC) and incorporating different iron content The materials were characterised using different techniques including N2 adsorption/desorption, X-ray diffraction (XRD), X-ray photoelectronic spectroscopy (XPS), Scanning Electron Microscopy coupled with energy dispersive X-ray analysis for elemental analysis (SEM-EDX), Transmission Electron Microscopy (TEM) and magnetic susceptibility. The magnetic nanocatalysts have demonstrated a high catalytic activity and chemical stability, highlighting their separation/reusability capacity in the selective oxidation reactions of isoeugenol (oxidative rupture) and vanillin alcohol (oxidation) to vanillin. The origin of its catalytic properties has been related to the surface concentration of iron nanoparticles and the Al-Fe interaction in the materials. Finally, a reuse study of the nanocatalysts has been carried out, demonstrating the stability of these systems under the investigated reaction conditions exhibiting similar catalytic activities after five uses. Lastly, the paper “Post-synthetic mechanochemical incorporation of Al species into the framework of porous materials: towards more sustainable redox chemistries” (Chapter III.3), different nanomaterials have been synthesized incorporating low aluminium contents (typically 0.2-0.4 wt.%) via mechanochemical milling and impregnation on mesoporous materials. Specifically, the incorporation of aluminium species was carried out using different sources such as aluminium isopropoxide and aluminium-containing MOFs materials. The physico-chemical properties of all materials were studied using characterization techniques including X-ray diffraction (XRD), adsorption-desorption of N2, scanning electron microscopy coupled with energy dispersive X-ray analysis for elemental analysis (SEM-EDX), inductively coupled plasma mass spectrometry (ICP-MS), pulse chromatography with pyridine and dimethyl pyridine as titration bases, magnetic nuclear resonance (NMR) and magnetic susceptibility studies. Solid state NMR studies pointed to different aluminium coordination states in the synthesised material, including framework aluminium species which strongly suggested that the mechanochemical procedure was able to introduce aluminium species within SBA-15 and MCM-41 post-synthetically with low Al content, being the first literature report on such post-synthetic mechanochemically assisted framework incorporation of catalytically active species in mesoporous materials. Despite the extremely low contents in Al (0.2-0.4% by weight), the isolated species of aluminum show promising catalytic activities in selective oxidation reactions using mild reaction conditions (microwave irradiation and mechanochemical milling) including the oxidations of benzyl alcohol to benzaldehyde, isoeugenol to vanillin and diphenyl sulfide to diphenyl sulfoxide

Fe-Containing MOFs as Seeds for the Preparation of Highly Active Fe/Al-SBA-15 Catalysts in the N-Alkylation of Aniline

We have successfully incorporated iron species into mesoporous aluminosilicates (AlSBA15) using a simple mechanochemical milling method. The catalysts were characterized by nitrogen physisorption, inductively coupled plasma mass spectrometry (ICP-MS), pyridine (PY) and 2,6-dimethylpyridine (DMPY) pulse chromatography titration, powder X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDX). The catalysts were tested in the N-alkylation reaction of aniline with benzyl alcohol for imine production. According to the results, the iron sources, acidity of catalyst and reaction conditions were important factors influencing the reaction. The catalyst showed excellent catalytic performance, achieving 97% of aniline conversion and 96% of imine selectivity under optimized conditions

Mechanochemically Synthesized Supported Magnetic Fe-Nanoparticles as Catalysts for Efficient Vanillin Production

Magnetically separable nanocatalysts were synthesized by incorporating iron nanoparticles on a mesoporous aluminosilicate (Al-SBA-15) through a mechanochemical grinding pathway in a single step. Noticeably, magnetic features were achieved by employing biomass waste as a carbon source, which additionally may confer high oxygen functionalities to the resulting material. The resulting catalysts were characterized using X-ray diffraction, X-ray photoelectron spectroscopy, transmission electron microscopy, scanning electron microscopy, porosimetry, and magnetic susceptibility. The magnetic nanocatalysts were tested in the selective oxidative cleavage reaction of isoeugenol and vanillyl alcohol to vanillin. As a result, the magnetic nanocatalysts demonstrated high catalytic activity, chemical stability, and enormous separation/reusability qualities. The origin of catalytic properties and its relationship with the iron oxide precursor were analyzed in terms of the chemical, morphological, and structural properties of the samples. Such analysis allows, thus, to highlight the superficial concentration of the iron entities and the interaction with Al as key factors to obtain a good catalytic response

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

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

Evolution over Time of Ventilatory Management and Outcome of Patients with Neurologic Disease∗

OBJECTIVES: To describe the changes in ventilator management over time in patients with neurologic disease at ICU admission and to estimate factors associated with 28-day hospital mortality. DESIGN: Secondary analysis of three prospective, observational, multicenter studies. SETTING: Cohort studies conducted in 2004, 2010, and 2016. PATIENTS: Adult patients who received mechanical ventilation for more than 12 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 20,929 patients enrolled, we included 4,152 (20%) mechanically ventilated patients due to different neurologic diseases. Hemorrhagic stroke and brain trauma were the most common pathologies associated with the need for mechanical ventilation. Although volume-cycled ventilation remained the preferred ventilation mode, there was a significant (p < 0.001) increment in the use of pressure support ventilation. The proportion of patients receiving a protective lung ventilation strategy was increased over time: 47% in 2004, 63% in 2010, and 65% in 2016 (p < 0.001), as well as the duration of protective ventilation strategies: 406 days per 1,000 mechanical ventilation days in 2004, 523 days per 1,000 mechanical ventilation days in 2010, and 585 days per 1,000 mechanical ventilation days in 2016 (p < 0.001). There were no differences in the length of stay in the ICU, mortality in the ICU, and mortality in hospital from 2004 to 2016. Independent risk factors for 28-day mortality were age greater than 75 years, Simplified Acute Physiology Score II greater than 50, the occurrence of organ dysfunction within first 48 hours after brain injury, and specific neurologic diseases such as hemorrhagic stroke, ischemic stroke, and brain trauma. CONCLUSIONS: More lung-protective ventilatory strategies have been implemented over years in neurologic patients with no effect on pulmonary complications or on survival. We found several prognostic factors on mortality such as advanced age, the severity of the disease, organ dysfunctions, and the etiology of neurologic disease