Modulación de la mesoestructura y composición en sílices nanoparticuladas con porosidad jerárquica

Dentro de la amplia variedad de materiales porosos, y más concretamente mesoporosos, las sílices mesoporosas bimodales nanopartículadas (NBS, en sus siglas en inglés) han despertado un gran interés en los últimos años. La síntesis de NBS fue por primera vez descrita por Zhang y col., quienes prepararon los materiales hexagonales de sílice (HMS, en sus siglas en inglés) empleando un único surfactante no iónico. Más tarde, ambos Ågre y col. y Haskouri y col. publicaron el uso de un surfactante catiónico (bromuro de cetiltrimetilamonio (C16TMABr)) para sintetizar materiales NBS tipo MCM-41 y tipo UVM-7. En estos trabajos se establecieron como claves diferentes variables procedimentales para la generación de la porosidad interpartícula (textural): la polaridad del medio en el caso de los materiales HMS y el pH de la solución inicial para las sílices tipo MCM-41. Las sílices tipo UVM-7 se diferencian fundamentalmente de las MCM-41 en su naturaleza nanoparticuladas. Al estar constituido por partículas nanométricas, los poros que contienen son también nanométricos (mucho más cortos que en el caso de la MCM-41, y más accesibles por tanto). Como su síntesis conlleva el uso de precursores atranos, es posible incorporar mayor cantidad de metales en la red inorgánica, con mayor homogeneidad composicional y reproducibilidad, como el material Ti-UVM-7, que presenta excelentes resultados en catalisis. Los objetivos de la tesis fueron los siguientes: 1) Lograr el desarrollo de un procedimiento de síntesis reproducible de sílices NBS, tipo UVM-7, que permita el control fino e independiente de ambos sistemas de poro, el intra y el interpartícula. Se pretende corroborar que mediante un control de las variables procedimentales fisicoquímicas como la concentración de surfactante y la constante dieléctrica del medio de reacción, junto a una estrategia de síntesis bien definida y simple, puede conducir a la obtención de unas sílices NBS que muestren unas características topológicas significativamente diferentes. 2) La síntesis de nuevos materiales mesoporosos bimodales nanopartículados , tipo UVM-7, empleando una fuente de silicio barata y simplificando al máximo la síntesis. Partiendo de un precursor inorgánico barato como el silicato sódico, se busca una vía de síntesis sencilla, reproducible, rápida y con el menor numero posibles de pasos de reacción, con vistas a una futura producción a nivel industrial de la sílice mesoporosa nanoparticulada. 3) Una caracterización detallada del nuevo material denominado UVM-10. Comprobar la semejanzas y diferencias de esta sílice mesoporosa nanoparticulada obtenida a partir de una fuente de silicio barata, con respecto a los materiales referencia (UVM-7 y MCM-41). El estudio de la UVM-10 se ha llevado a cabo mediante todas las técnicas de caracterización de sólidos mesoporosos disponibles en el ICMUV. 4) Dentro de una caracterización y adecuación de la UVM-10 para su aplicación futura como soporte catalítico, se han estudiado las posibles vías de síntesis y su posterior optimización que permitan la obtención de la sílice UVM-10 dopada con diversos heteroelementos (Al y Ti). 5) Se ha traslado el conocimiento químico adquirido a la posibilidad de obtener un material nanoparticulado con porosidad jerárquica bimodal a partir de una fuente de silicio condensada pero mediante una vía de síntesis que transcurra en fase homogénea. Este material pasará a denominarse sílice tipo UVM-12. 6) Por último, se ha planteado un estudio de estabilidad térmica comparativo entre las diferentes sílices, (UVM-7,UVM-10 y UVM-12). En general, el ánimo principal del trabajo se ha dividido en dos partes; en el caso de la UVM-7, la máxima comprensión de los procesos implicados en la síntesis (especialmente hidrólisis, condensación y redisolución de la sílice) y estudiar cómo afecta una regulación eficiente de dos variables procedimentales fisicoquímicas básicas: la concentración de surfactante y la constante dieléctrica del medio de reacción. Y en una segunda parte, la obtención de nuevos materiales siguiendo las premisas de abaratar la síntesis, simplificar el proceso y eliminar reactivos dañinos para el medioambiente. Ambas partes con la premisa de comprender mejor los sistemas químicos implicados y adecuar las síntesis a una posible futura transferencia de estos productos a la industria. Las etapas seguidas en la obtención de los diferentes productos han sido; 1) Establecer las condiciones óptimas de síntesis 2) Síntesis de los materiales y control de las variables del proceso 3) Tratamiento post-síntesis que incluye el lavado del material para eliminar restos de reactivos y la calcinación para eliminar el surfactante o extracción química con etanol. 4) Caracterización de los materiales. Los medios comúnmente empleados han sido la difracción de Rx de polvo, porosimetría, microscopía electrónica de transmisión (TEM) o de barrido (SEM), resonancia magnética nuclear de sólidos (29Si, 27Al), análisis por EDX. Podemos concluir que: 1-Las sílices UVM-7 y UVM-10 combinan todas las ventajas asociadas a mesoporos cortos en longitud, interconectados y con una porosidad jerárquica a mayor escala. 2-Por primera vez se ha modulado el tamaño de los dos sistemas de poro de forma independiente con un único surfactante mediante una síntesis tipo one-pot. 3-Se han preparado por primera vez sílices tipo NBS a partir de silicato sódico con rendimientos apreciables y propiedades texturales similares a las que presenta la sílice UVM-7 a las que hemos denominado tipo UVM-10. Además, se ha modulado la porosidad intra e interpartícula empleando también un único agente plantilla. Se ha compatibilizado esta nueva vía preparativa low-cost con la inclusión de cantidades apreciables de aluminio y titanio como heteroelementos, sin alterar la organización NBS. 4-Modificando el orden de adición de los reactivos respecto al empleado en la síntesis de las sílices UVM-10, hemos conseguido sintetizar mediante una estrategia one-pot una nueva familia, sílices UVM-12, que combina ventajas de sus dos predecesores (UVM-7 y UVM-10). Se ha optimizado también la incorporación de heteroelementos (Al y Ti) que modifican la naturaleza de la pared de mesoporo, manteniendo la organización tipo NBS. 5-Ne ha preparado una nueva familia de sílices NBS , UVM-13, empleando un único agente plantilla para generar dos sistemas de poro jerárquicos, empleado una fuente de sílice sólida como la sílice fumed. 6-Hemos modulado el tamaño de pared en sílices tipo NBS desde aproximadamente 1.9 nm (UVM-7) hasta 2.9 (UVM-13), pasando por 2.5 (UVM-10). La importancia de este parámetro radica en que a mayor espesor tenemos mayor estabilidad térmica y este punto podría paliar en cierta medida la deficiencia de las sílices mesoporosas sobre las zeolitas. La comprensión de las reacciones implicadas en los distintos procesos de síntesis es lo que ha permitido dirigir nuestra química preparativa para obtener materiales con características específicas, homogéneos química y estructuralmente y de forma reproducible. Estas características se convierten en requisitos necesarios e indispensables si pensamos en la posibilidad de emplear estas sílices NBS como plataforma o sistema soporte de estructuras más complejas (materiales teranósticos, catalizadores, composites, etc.), o si queremos escalar su síntesis pensando en posibles transferencias a sectores productivos. Los nuevos soportes UVM-10 y UVM-12 podrían mejorar las prestaciones, sobre todo en aquellos casos en los que se requiera (por las condiciones de uso) una estabilidad térmica o hidrotermal superior. De entre las aplicaciones donde estos sólidos pueden resultar interesantes, cabe destacar todas aquellas donde se requieran grandes cantidades (debido a su menor precio), como por ejemplo catálisis y remediación. En otros casos, como en medicina, probablemente el coste de la sílice no será lo que incremente el valor del producto final.Among the wide variety of porous materials, specifically mesoporous, nanoparticulate bimodal silicas (NBS) have attracted considerable interest in the last years. NBS synthesis was first described by Zhang et al. who synthesized the hexagonal silica materials (HMS) using a single nonionic surfactant. Later, both Agre et al. and Haskouri et al. reported the use of a cationic surfactant (cetyltrimethylammonium bromide (C16TMABr)) for synthesizing NBS materials like MCM-41 and UVM-7. In these works they established different procedural variables keys for interparticle porosity (texture) generation: the medium polarity in the case of HMS materials and pH of the initial solution for the silica type MCM-41. The type UVM-7 silicas are fundamentally different from the MCM-41 in their nanoparticulate nature. As they are composed of nanometric particles, the pores they contain are also nanometer (much shorter than in the case of MCM-41, and therefore more accessible). As their synthesis involves the use of atrane precursors, it is possible to incorporate more metals in the inorganic network, with more compositional homogeneity and reproducibility, like the Ti-UVM-7 material, which has excellent results in catalysis. The aims of this thesis were: 1- To ensure the development of a reproducible method of synthesis of NBS silica, UVM-7-like, to enable a fine and independent control, of both intra- and interparticle pore systems. It is intended to confirm that by controlling the physicochemical procedural variables as the concentration of surfactant and the dielectric constant of the reaction, along with a well-defined and easy synthesis strategy, a NBS silica showing topological significantly different characteristics can be obtained. 2- To synthesize new nanoparticulated bimodal mesoporous materials, like UVM-7, using a cheap source of silica by simplifying the maximum the synthesis. Starting from a cheap inorganic precursor such as sodium silicate, look for a path of simple, reproducible, fast and with the least possible number of synthesis reaction steps with a view to future production at industrial level of the nanoparticulate mesoporous silica. 3- A detailed characterization of a new material called UVM-10. Check the similarities and differences of this nanoparticulate mesoporous silica obtained from a cheap source of silica with respect to the reference materials (UVM-7 and MCM-41). The study of UVM-10 was carried out by all mesoporous solid characterization techniques available in the ICMUV. 4- Within a characterization and adequacy of the UVM-10 for future application as catalyst support, we have studied the possible routes of synthesis and its subsequent optimization that will produce synthesis of the UVM-10 silica doped with various heteroelements (Al and Ti) . 5- The chemical knowledge acquired has been transferred to the ability to obtain a nanoparticulate hierarchical bimodal porosity material from condensed silica but by a synthesis route that occurs in an homogeneous phase. This material was named silica type UVM-12. 6- Finally, it has been raised a comparative thermal stability between the different silicas (UVM-7, UVM-UVM-10 and 12). In general, the aim of this work has been divided into two parts; in the case of the UVM-7, it was the maximum understanding of the processes involved in the synthesis (especially hydrolysis, condensation and reconstitution of silica) and to study how affects an efficient procedural regulation of the two physicochemical basic variables: the concentration of surfactant and dielectric constant of the reaction medium. In a second part, we look for the development of new materials following the premises of reducing the synthesis, simplifying the process and eliminating the environmentally harmful reagents. Both parts have been done for a better understanding of the chemical synthesis systems involved and the adaptation to a possible future transfer of these products to the industry. The steps followed in obtaining the different products have been: 1) Establish the optimal synthesis conditions 2) Synthesis of materials and control of process variables 3) Post-synthesis treatment which includes washing the material to remove any reagents and the calcination to remove the surfactant or the chemical extraction with ethanol. 4) Materials characterization. The commonly employed means were the powder X-ray diffraction, porosimetry, transmission electron microscopy (TEM) or (SEM), solid nuclear magnetic resonance (29Si, 27Al), EDX analysis. We can conclude that: 1-The UVM-7 and UVM-10 silicas combine all the advantages associated with short in length, interconnected with a hierarchical porosity and larger scale mesopores. 2-For the first time it has been modulated the two systems pore size independently with a single surfactant by one-pot synthesis. 3-For the first time NBS were prepared from sodium silicate with appreciable yield and textural properties similar to those presented by the UVM-7 silica; they were named UVM-10. In addition, intra- and interparticle porosity has been modulated using a single template agent. It has combined this new low-cost preparative synthesis with the inclusion of substantial amounts of aluminum and titanium without altering the NBS organization. 4- Modifying the order of addition of the reagents with respect to the used in the UVM-10 silicas synthesis, we managed the one-pot strategy synthesis of a new silicas family, the UVM-12, which combines the advantages of its two predecessors (UVM-7 and UVM-10). The incorporation of heteroatoms (Al and Ti) which modify the nature of the mesopore wall was also optimized but keeping the NBS type organization. 5- A new family of NBS silica, UVM-13, was synthesized using as a source of solid silica the fumed silicas and a single agent template to generate two hierarchical pore systems. 6- We modulated the NBS wall size from about 1.9 nm (UVM-7) to 2.9 (UVM-13) through 2.5 (UVM-10). The importance of this parameter is that thegreater is thethickness the higher thermal stability is and this point could overcome the deficiency of mesoporous silicas on zeolites. Understanding the reactions involved in the different synthesis processes has allowed us to direct our preparative chemistry to obtain materials with specific characteristics, chemical and structural homogeneity, and in reproducible way. These features become necessary and indispensable requirements if we consider the possibility of using these NBS solids as platform or support system for more complex structures (theranostics materials, catalysts, composites, etc.), or if we want to scale their synthesis thinking about possible transfers to productive sectors. The new UVM-10 and UVM-12 materials could improve performance on especially in those cases where it is required (by the conditions use) thermal or hydrothermal stability higher. Of between the applications where these solids may be of interest, it highlighting all those where large quantities are required (due to its lower price), such as catalysts and remediation. In other cases, such as in medicine, probably the increased cost for using silica will not be important in the value of the final product

Metabolic Profile of chronic liver disease by NMR spectroscopy of human biopsies

Abstract Among the different processes occurring during the evolution of liver disease, fibrosis has a predominant role. Liver fibrosis mechanisms are fairly constant irrespective of the underlying etiology. Cirrhosis is the end-stage of this reaction. Metabolic profiles, which are affected by many physiological and pathological processes, may provide further insight into the metabolic consequences of this severe liver disease. The aim of this study was to demonstrate the applicability of 1H high resolution magic angle spinning (HR-MAS) NMR spectroscopy in the biochemical profile determination of human liver needle biopsy samples for the characterization of metabolic alterations related to the severity of liver disease. We recorded and analyzed HR-MAS spectra of 68 liver tissue samples obtained by needle biopsy from patients with chronic liver disease. Multivariate analysis was applied to these data to obtain discrimination patterns and to reveal relevant metabolites. The metabolic characterization of liver tissue from needle biopsies by HR-MAS NMR spectroscopy provided differential patterns for cirrhotic and non-cirrhotic chronic liver disease tissue. Metabolites closely related to the liver metabolism such as some fatty acids, glucose and amino acids show differences between the two groups. Phospholipid precursors, which have been previously correlated with hepatic lesions also show differences. Furthermore, the correlation between histologically assessed liver disease stages and the levels of the most discriminative metabolites show that liver dysfunction is present at the initial stages of chronic hepatic lesions. Overall, this work suggests that the additional information obtained by NMR metabolomics applied to needle biopsies of human liver may be useful for assessing metabolic alterations and liver dysfunction in chronic liver disease

4to. Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad. Memoria académica

Este volumen acoge la memoria académica de la Cuarta edición del Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad, CITIS 2017, desarrollado entre el 29 de noviembre y el 1 de diciembre de 2017 y organizado por la Universidad Politécnica Salesiana (UPS) en su sede de Guayaquil. El Congreso ofreció un espacio para la presentación, difusión e intercambio de importantes investigaciones nacionales e internacionales ante la comunidad universitaria que se dio cita en el encuentro. El uso de herramientas tecnológicas para la gestión de los trabajos de investigación como la plataforma Open Conference Systems y la web de presentación del Congreso http://citis.blog.ups.edu.ec/, hicieron de CITIS 2017 un verdadero referente entre los congresos que se desarrollaron en el país. La preocupación de nuestra Universidad, de presentar espacios que ayuden a generar nuevos y mejores cambios en la dimensión humana y social de nuestro entorno, hace que se persiga en cada edición del evento la presentación de trabajos con calidad creciente en cuanto a su producción científica. Quienes estuvimos al frente de la organización, dejamos plasmado en estas memorias académicas el intenso y prolífico trabajo de los días de realización del Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad al alcance de todos y todas

Developing experimental design and analysis skills in Biomedical Engineering. A laboratory experiment proposal

[EN] Learning-teaching process in the area of Biomedical Engineering requires the acquisition of skills related to the formulation and resolution of problems in biology and medicine through the use of innovative technologies, and the ability to effectively use biomedical instrumentation and the processing and analyzing methods for studying the complex systems and processes of the human body. In order to deepen the acquisition of some omics-related disciplines, the objective of the present work is the development of a laboratory experiment in the field of molecular imaging, whose purpose is the metabolomic study (acquisition and data processing) of biological samples by Nuclear Magnetic Resonance (NMR) spectroscopy. The proposed laboratory experiment is carried out in groups of 15 students and it is structured in two different sessions. The first session is held at the facilities of the Molecular and Metabolomic Imaging Laboratory of the Unitat Central d¿Investigació de Medicina of University of Valencia, and during the session each student performs the sample collection and treatment of their own biological sample (urine), whose metabolomic study is desired, following the appropriate laboratory protocol. After preparation, the acquisition of the NMR spectra corresponding to each of the samples is carried out. All students introduce their samples into the NMR spectrometer and observe the different phases of the acquisition process (frequency tuning and matching, sequence specification, pulse calculation, etc.) to obtain the NMR spectrum. In the second session, which takes place in a computer classroom of the Universitat Politècnica de València, the purpose is the use of different methods of analysis and observation to identify and quantify the metabolites from the NMR spectra acquired during the first session. Firstly, signal processing techniques are used to process the NMR spectra (phase correction, baseline correction and spectrum reference), and then a total of 10 selected metabolites contained in the urine are quantified, using specific software for its application to the field of metabolomics. Finally, the students create a table that collects the data of the subjects (themselves, anonimized) and metabolite concentration, and perform the multivariate statistical analysis: principal component analysis (PCA) and partial least squares discriminant analysis (PLSDA). Through the performed analysis, each student establishes one metabolic profile and obtains conclusions from it, such as the determination of a characteristic metabolomic fingerprint associated with variables such as the sex of the person providing the sample, or the determination of a smoker profile, among others. Through the completion of the proposed laboratory experiment, students will acquire general and specific outcomes in the Biomedical Engineering field: 1) implementation and management of adequate experiments (preparation of biological samples), 2) use of innovative technologies (process of acquisition of NMR spectra), 3) application of scientific methods to perform the analysis of data (signal processing), 4) selection and performance of observation methods (statistical analysis) to assess the results and build conclusions, 5) to carry out a simple metabolic study that allows to verify the metabolic impact of some variable as smoking, and 6) to propose new working hypotheses based on the results obtained and expected results.This work was supported by Conselleria d¿Educació of Generalitat Valenciana [grants number GV/2018/111 and APOSTD/2018/181] and Instituto de Salud Carlos III-FEDER (Fondo Europeo de Desarrollo Regional) [grant number CB16/11/00486].Del-Canto, I.; Morales-Tatay, JM.; Moratal, D. (2020). Developing experimental design and analysis skills in Biomedical Engineering. A laboratory experiment proposal. IATED. 5120-5129. https://doi.org/10.21125/inted.2020.1393S5120512

Salivary metabolomic profile associated with cariogenic risk in children

Objectives: To identify the metabolomic differences in the saliva of healthy children versus children with active carious lesions and to estimate the predictive capacity of a model based on the salivary metabolomic profile. Methods: A study of cases (n =31) and controls (n =37) was designed for children aged between 6 and 12 (mean age of the cases: 8.9; controls: 8.7). The said children attended public health centers in Valencia, Spain. Intraoral examinations were performed by a single examiner using ICDAS II diagnostic criteria. Unstimulated total saliva samples were analyzed by nuclear magnetic resonance (NMR) spectroscopy. Results: The dft index for cases was 2.84 while it was 0.19 for the control group, the DMFT index was 1.13 and 0.11, respectively. The predictive model generated by the multivariate PLS-DA analysis projects a separation between the cases and the controls on the score chart with a predictive capacity and generating an area under the curve of 0.71. The metabolites: 3-methyl-2-oxovalerate, 3-hydroxybutyrate, lactate, acetone, citrate, ornithine, ethanolamine, taurine, proline, glycine, mannose, glucose, 1-6-Anhydro-β-D-glucose and citraconate, are those that show greater significance in the model. In the controls, glycine (Cohen's d =0.430) and glucose (Cohen's d =0.560) present higher means compared to the cases. On the contrary, taurine (Cohen's d=-0.474) and mannose (Cohen's d=-0.456) show higher means in cases compared to controls. Conclusions: Our findings show a difference in the salivary metabolomic profiles, specifically in the groups of saccharides and amino acids, suggesting an association of these with the level of caries risk. Clinical significance: The results reported in the present study reinforce the use of salivary metabolomics as a research method for the search for salivary biomarkers that allow the evaluation of caries risk in patients. Furthermore, it brings us closer to a personalized medicine that will help in dental caries prevention strategies

Scale-up low-cost synthesis of bimodal mesoporous silicas

Porous pure and doped silicas with pore sizes at two length scales (meso/macroporous) have been prepared through a large scale one-pot surfactant assisted reproducible procedure by using a simple template agent and starting from non-expensive sodium silicate as silicon source. Together with the relative low-cost of the reagents we have used, the simplicity of this method, which moreover is scalable and provides high yields, could be a strong argument for considering its suitability for the production of bimodal porous silicas. Additionally, we present a simple chemical scheme that allows directing the synthesis towards different related materials including both bimodal nanoparticulated mesoporous materials and unimodal particulate silica gels or MCM-41-like solids

Metabolites identified and compared attending the periodontal satatus.

<p>* p < 0.05 and ** p < 0.01.</p

Using NMR in saliva to identify possible biomarkers of glioblastoma and chronic periodontitis

<div><p>Nowadays there is increasing interest in identifying–and using–metabolites that can be employed as biomarkers for diagnosing, treating and monitoring diseases. Saliva and NMR have been widely used for this purpose as they are fast and inexpensive methods. This case-control study aimed to find biomarkers that could be related to glioblastoma (GBL) and periodontal disease (PD) and studied a possible association between GBL and periodontal status. The participants numbered 130, of whom 10 were diagnosed with GBL and were assigned to the cases group, while the remaining 120 did not present any pathology and were assigned to the control group. On one hand, significantly increased (p < 0.05) metabolites were found in GBL group: leucine, valine, isoleucine, propionate, alanine, acetate, ethanolamine and sucrose. Moreover, a good tendency to separation between the two groups was observed on the scatterplot of the NMR. On the other hand, the distribution of the groups attending to the periodontal status was very similar and we didn´t find any association between GBL and periodontal status (Chi-Square 0.1968, p = 0.91). Subsequently, the sample as a whole (130 individuals) was divided into three groups by periodontal status in order to identify biomarkers for PD. Group 1 was composed of periodontally healthy individuals, group 2 had gingivitis or early periodontitis and group 3 had moderate to advanced periodontitis. On comparing periodontal status, a significant increase (p < 0.05) in certain metabolites was observed. These findings along with previous reports suggest that these could be used as biomarkers of a PD: caproate, isocaproate+butyrate, isovalerate, isopropanol+methanol, 4 aminobutyrate, choline, sucrose, sucrose-glucose-lysine, lactate-proline, lactate and proline. The scatter plot showed a good tendency to wards separation between group 1 and 3.</p></div

Metabolites identified and compared between GBM and control groups.

<p>* p < 0.05 and ** p < 0.01.</p

Distribution of case and control groups attending to the periodontal status.

<p>Distribution of case and control groups attending to the periodontal status.</p