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Los capítulos 1,2 y 3 están sujetos a confidencialidad por el autor. 103 p., El presente trabajo de investigación recoge el estudio y desarrollo de nuevas metodologías sintéticas basadas en procesos en cascada a partir de la cicloisomerización de ácidos alquinoicos catalizada por cobre. Además de un estudio más pormenorizado de dicha reacción clave, se presenta el resultado de la interacción de las alquilidenlactonas intermedias con nucleófilos simples, como aminas y alcoholes, así como con aminoacetales, junto con el estudio de transformaciones one-pot que pueden realizarse en algunos de los productos resultantes. Asimismo, se presentan los resultados obtenidos en el contexto de una estancia predoctoral de 3 meses en el grupo de investigación del Prof. Dr. Burkhard König en la Universidad de Regensburg, Alemania. En dicha estancia se colaboró en el desarrollo de una metodología foto-inducida para la homologación de compuestos carbonílicos.

239 p., Esta tesis doctoral se fundamenta en el desarrollo de materiales metal-orgánicos porosos como son las redes metal-orgánicas (metal-organic frameworks, MOFs), los geles metal-orgánicos (metal-organic gels, MOGs) y los aerogeles metal-orgánicos (metal-organic aerogels, MOAs), que han sido utilizados a lo largo del trabajo en la valorización de CO2, la adsorción de agua y la producción fotocatalítica de hidrógeno. Cada tipo de material ha sido diseñado específicamente para obtener el mejor rendimiento en las siguientes aplicaciones: (i) MOFs heterometálicos de Cu(II) para la conversión electroquímica de CO2 a alcoholes, (ii) MOFs robustos de Zr(IV) y Hf(IV) para mejorar la estabilidad tanto durante la conversión electroquímica de CO2 como en la adsorción de vapor de agua, y (iii) MOGs y MOAs de Ti(IV) para la reducción de CO2 y la producción de hidrógeno fotoquímicas.En este sentido, la primera parte de la tesis (Capítulo 3) describe la síntesis y el comportamiento electroquímico de MOFs basados en cobre (HKUST-1(Cu,MD)) y mezclas de MOFs HKUST-1(Cu) yCAU-17(Bi), que a pesar dar lugar a velocidades de reacción y eficiencias faradaicas mucho mayores que otras redes metal-orgánicas analizadas previamente, carecen de estabilidad a largo plazo. Por esta razón, en el Capítulo 4, se sintetiza una nueva familia de MOFs robustos de Zr(IV) y Hf(IV) y ligandos dicarboxilato (benceno-1,4-dicarboxilato, BDC, y 2-aminobenceno-1,4-dicarboxilato, NH2BDC), denominada familia EHU-30 (de Euskal Herriko Unibertsitatea). Su rendimiento como catalizadores electroquímicos en la reducción de CO2 no supera los resultados obtenidos con la familia HKUST-1, pero las velocidades de producción y eficiencias faradaicas no decaen a lo largo del tiempo de reacción explorado (400 min), lo que se puede atribuir a una mayor estabilidad de la red de coordinación. Así mismo, se evalúa su capacidad como adsorbentes de vapor de agua, presentando un carácter más hidrofílico que su familia de polimorfos, deno

115 p., La creciente demanda de almacenamiento de electricidad en todo el mundo exige soluciones tecnológicas capaces de satisfacer con seguridad estas necesidades. Las baterías son un candidato relevante como sistema de almacenamiento de energía debido a su alta densidad energética y su eficiente almacenamiento orientado a corto-medio plazo (minutos-horas). En la actualidad, los principales retos se centran en continuar aumentando la densidad energética y mejorar su seguridad.Las baterías de iones de litio son la tecnología más implantada en los últimos 10 años debido a su densidad energética. Sin embargo, la actual tecnología ha quedado limitada a ~700 Wh L-1, lo que refleja una limitación en una autonomía de los vehículos eléctricos de ~500 km. Además, los requisitos de seguridad en los vehículos eléctricos se ven comprometidos debido al uso de electrolitos líquidos basados en compuestos orgánicos volátiles que presentan riesgo en caso de incendio o fuga.Las baterías de Li metálico en estado sólido que contienen electrolitos poliméricos son una alternativa prometedora debido a su menor flamabilidad, facilidad de procesado y contacto con el material electroactivo. Además, las SSLMBs se consideran una tecnología que habilita el uso de los electrodos de Li metal, debido a su gran estabilidad y a la formación de una interfaz estable, lo que conduce a altos valores de densidad energética teórica en comparación con la tecnología comercial actual.Esta tesis se centra en resolver problemas relacionados con la estabilidad electroquímica y la conductividad iónica en baterías de Li metálico en estado sólido con electrolitos poliméricos. Esto se lleva a cabo mediante un novedoso método de combinación de polímeros en la batería, denominado Double Layer Polymer Electrolyte (DLPE).

Glycans are everywhere in Nature, where they play a plethora of functions in every domain of life. The recognition of glycans by lectins is at the heart of a myriad of biological proceses, including host-pathogen interactions, which have made them essential targets in the field of drug discovery. In this context, the main focus of this Thesis has centred on unravelling of the conformational and structural properties of the recognition of a battery of natural and synthetically obtained glycans to two specific human lectins, galectin-8 and DC-SIGN. This analysis has been performed employing a synergic combination of NMR-based methods, assisted by other experimental methods (ITC) and computational tools (Molecular Dynamics simulations).

Los capítulos 5 y 6 están sujetos a confidencialidad por la autora. 140 p., El trabajo aquí presentado proporciona nuevas herramientas para optimizar nuevos biocatalizadores heterogéneos, abriendo un nuevo camino para el control racional de la orientación de las enzimas. Además, introdujimos un ensayo múltiple diseñado para seguir la cinética de las transaminasas. A través de estos esfuerzos, presentamos dos dispositivos diseñados para la selección de diversas enzimas, químicas de inmovilización y soportes. Esta contribución mejora el panorama en constante evolución del diseño de procesos enzimáticos. Además, los microdispositivos y la detección fluorométrica ofrecen un marco dinámico para una investigación profunda de los biocatalizadores, elucidando la complicada interacción entre los soportes de inmovilización, las configuraciones de los reactores y los modos operativos.

315 p., Glycans are ubiquitous molecules in nature. They participate in a plethora of functions, they cover the surface of cells as integral constituents of complex glycoconjugates (glycoproteins, and glycolipids) forming the glycocalyx. The molecular recognition of glycans by lectins is a finely tuned process where even the most minimal change within the recognized glycan structure can lead to drastic changes within the meticulously orchestrated symphony of life. For that reason, understanding the structure, dynamics, and interactions of glycans is of paramount importance for being able to modulate biological events related to health and disease. In this Thesis, I have employed a synergic combination of advanced NMR spectroscopy and X-ray crystallography methods with biophysical techniques, assisted by computational chemistry tools to elucidate the intricate process of molecular recognition of glycans.

Stable palladium (II) complexes, incorporating a double (N-benzoylthiourea) arrangement bonded to a complex heterocyclic scaffold, are used as precursors of catalytic species able to promote Suzuki–Miyaura, Mizoroki–Heck, Hiyama, Buchwald–Hartwig, Hirao and Sonogashira–Hagihara cross-coupling transformations in water. These sustainable processes are chemoselective and very versatile. The nanoparticles responsible for these catalytic reactions were analyzed and studied. Their usefulness is demonstrated after several tests and analyses. The heterogeneous character of this species in water was also confirmed.

The study of new catalytic protocols for the synthesis of organic compounds with a more sustainable perspective is of interest. The use of ionic organic solids, such as 1,3-bis(carboxymethyl)imidazolium chloride as a catalyst has allowed the Michael addition of N-heterocycles to chalcones. This methodology has been applied to the unique preparation of the potential bioactive compound 1-(3,4-dimethoxyphenyl)-3-(4-methoxyphenyl)-3-(1H-1,2,4-triazol-1-yl)propan-1-one with moderate yield, due to the retro-Michael reaction. Both synthetic reactions (i.e., preparation of chalcone and triazole Michael-addition to chalcone) have good green metrics.

Zeolitic imidazolate framework-67 (ZIF-67) functionalized with graphene quantum dots was prepared and utilized for the reduction of Au (III) and stabilization of Au nanoparticles. This newly prepared ZIF-67/GQD@Au was characterized with different techniques and employed as a capable heterogeneous catalyst for reduction of aromatic nitro compounds and A1-coupling reaction of alkynes, amines, and aldehydes in water solvent. Experiments indicate that this catalyst is able to reduce nitroarenes in short reaction times (10–20 min) in water at room temperature and corresponding amines were obtained in excellent yields (90–100%). Also, reactions of structurally different alkynes, amines, and aldehydes in the presence of this catalyst proceed effectively at 60°C and desired propargylic amine achieved in good to very good yields (76–88%) in water during 1 day. This catalyst displayed excellent stability and recyclability in both reactions and recycled for six runs with a small decrease in the activity.

Herein, core–shell magnetic nanoparticles are modified with imidazolium-tagged phosphine and propylene glycol moieties and used for the stabilization of bimetallic AuCu nanoparticles. The structure and morphology of the prepared material are identified with SEM, TEM, XRD, XPS, atomic absorption spectroscopy, Fourier translation infrared spectroscopy, and a vibrating sample magnetometer. This hydrophilic magnetic bimetallic catalyst is applied in the reduction of toxic nitroarenes and reductive degradation of hazardous organic dyes such as methyl orange (MO), methyl red (MR), and rhodamine B (RhB), as well as in the degradation of tetracycline (TC). This magnetic AuCu catalyst indicated superior activity in all three mentioned reactions in comparison with its single metal Au and Cu analogs. This catalyst is recycled for 17 consecutive runs in the reduction of 4-nitrophenol to 4-aminophenol without a significant decrease in catalytic activity and recycled catalyst is characterized.

Multilayer graphene (MLG), obtained by mild sonication of graphite in NMP, was functionalised via 1,3-dipolar cycloaddition with azomethine ylides generated by thermal 1,2-prototropy from various imino esters. The microwave-assisted functionalisation took place in five hours at 100 °C. The resulting MLG, containing substituted proline-based amine functional groups, was characterized using XPS and showed a nitrogen loading three times that obtained for the same transformation performed for five days using convection-assisted heating. The preparation of the imino ester containing a bipyridine unit at the arylidene position allowed for the preparation of the corresponding functionalised MLG, which incorporated the ruthenium atom to achieve a heterogeneous MLG-Ru complex. This supported complex was tested, as a proof of concept, as a photocatalyst of the aerobic oxidative hydroxylation of 4-methoxyphenylboronic acid.

Addressing large bone segmental defects remains a profound challenge in orthopaedic surgery, demanding graft designs that mirror patient-specific defects while ensuring vascularization, osteoconduction, and structural integrity. Conventional approaches fall short in achieving this level of customization and functionality. This work leverages fuse filament fabrication (FFF) to fabricate innovative yttria stabilize zirconia graft designs that combine several strategies to tackle these multifaceted challenges. Graft designs ingeniously incorporate dense and porous structures mimicking the intricate architecture of natural bone for improved structural integrity and different ridges and protrusions to enhance the fixation. Additionally, these grafts undergo infiltration with PCL/PVA/AgNPs composite polymers, enriching biocompatibility, structural integrity, and antibacterial properties, fostering conducive conditions for optimal bone growth. Attaining printable filaments with YSZ powders below 50 nm and loads reaching 50 vol% marks a pioneering advancement in bone graft fabrication via Fused Filament Fabrication (FFF). This enabled high densification and low grain size at reduced sintering temperatures, imperative to achieve high mechanical performance. The biodegradation capacity of biopolymers in PBS and their role in the mechanical behaviour of grafts have been assessed, demonstrating the beneficial potential of the multicomponent graft proposed reaching strength values of 90–105 MPa.

En las últimas décadas se ha experimentado un avance notable en el diseño y preparación sistemas capaces de participar en procesos biológicos de una manera predecible y controlada, dotándoles de la habilidad de respuesta frente a estímulos con el objetivo de desarrollar de nuevas estrategias terapéuticas. En esta Tesis doctoral se ha propuesto la preparación de dos familias de sistemas: por un lado, transportadores de ácidos nucleicos basados en ciclodextrinas y, por otro, reguladores de la actividad de enzimas glicosidasas lisosomales basados en glicomiméticos de tipo sp2-iminoazúcar con potencial para uso como chaperonas farmacológicas. La terapia génica es una estrategia terapéutica con gran potencial cuyo éxito requiere el diseño de sistemas de transporte adaptados (vectores) capaces de compactar y proteger el material génico. En los últimos años se han desarrollado vectores no virales moleculares, con estructura perfectamente definida empleando como plataforma estructural ciclooligosacáridos de la familia de las ciclodextrinas. La estructura bifacial de las ciclodextrinas y la diferencia de reactividad entre los hidroxilos situados en una y otra cara (primaria y secundaria), nos ha permitido la incorporación de elementos funcionales con una orientación precisa sobre la estructura macrocíclica nanométrica. Aprovechando esta propiedad, a lo largo de esta Tesis se han desarrollado nuevos sistemas vectoriales de ácidos nucleicos, cuya organización resulta dependiente del pH. Por un lado, se han preparado una familia de ciclodextrinas con una anfifilia frustrada provocada por la disposición de cabezas catiónicas en ambas caras de la ciclodextrinas junto a la incorporación de cadenas grasas en una de estas caras. Además, se han preparado los respectivos controles que solo incorporaron los grupos ionizables. El análisis del proceso de autoensamblaje de estas moléculas y co-ensamblaje con ácidos nucleicos evidencian la importancia de esta disposición en la propiedades, In recent decades, there has been a significant advancement in the design and preparation of systems capable of participating in biological processes in a predictable and controlled manner, endowing them with the ability to respond to stimuli with the aim of developing new therapeutic strategies. In this doctoral thesis, the preparation of two families of systems has been proposed: on one hand, nucleic acid carriers based on cyclodextrins, and on the other hand, regulators of lysosomal glycosidase enzyme activity based on sp2-imino sugar-type glycomimetics with the potential for use as pharmacological chaperones. Gene therapy is a therapeutic strategy with significant potential, the success of which hinges on the design of tailored delivery systems (vectors) capable of compacting and protecting genetic material. In recent years, non-viral molecular vectors have been developed with a well-defined structure, using cyclodextrins from the cyclodextrin family as a structural platform. The bifacial structure of cyclodextrins and the difference in reactivity between the hydroxyl groups located on the primary and secondary faces have allowed us to incorporate functional elements with precise orientation on the nanometric macrocyclic structure. Leveraging this property, throughout this thesis, new nucleic acid vector systems have been developed, whose organization is pH-dependent. On one hand, a family of cyclodextrins with frustrated amphiphilicity has been prepared, induced by the arrangement of cationic heads on both faces of the cyclodextrins along with the incorporation of lipid chains on one of these faces. Additionally, the respective controls were prepared, which only included the ionizable groups. The analysis of the self-assembly process of these molecules and co-assembly with nucleic acids underscores the importance of this arrangement in the supramolecular properties of the nanocomplexes and their efficiency in transfection. In vitro transfection experiments conf

La presente Tesis Doctoral aborda la caracterización química de las ligninas y los lípidos presentes en diversos materiales lignocelulósicos, incluyendo tanto residuos derivados de la actividad agrícola (cascarilla y paja de arroz, y podas de naranjo) como cultivos agrícolas (tallo de papiros). La caracterización detallada de la composición y estructura de las ligninas se llevó a cabo utilizando técnicas analíticas avanzadas como la Cromatografía de Permeación en Gel (GPC), la Pirólisis acoplada a Cromatografía de Gases y Espectrometría de Masas (Py-GC/MS), la espectroscopía de Resonancia Magnética Nuclear bidimensional (2D-RMN), y métodos de degradación química como la Derivatización Seguida de Rotura Reductora (DFRC). Por otro lado, la composición química de los compuestos lipofílicos se analizó mediante cromatografía de gases acoplada a espectrometría de masas (GC/MS). Los resultados obtenidos del análisis de ligninas muestran que las ligninas de la cascarilla y la paja de arroz, así como la de las podas de naranjo estaban enriquecidas en unidades guaiacilo (G), con cantidades menores de p-hidroxifenilo (H) y siringilo (S). En cambio, se observaron grandes diferencias en las ligninas del tallo de papiro; mientras que la lignina de la corteza estaba enriquecida en unidades G, la lignina de la médula estaba enriquecida en unidades S. Además, las ligninas de la cascarilla y de la paja de arroz así como las de la corteza y la médula del tallo del papiro presentaban importantes cantidades de p-cumaratos y ferulatos incorporados en sus estructuras. Las diferencias en la composición de las ligninas se reflejaron en el contenido de los enlaces entre las unidades de lignina, teniendo las ligninas enriquecidas en unidades G una mayor contenido de enlaces condensados. Especialmente relevante fue el descubrimiento de diversos flavonoides como la naringenina chalcona, y las flavanonas naringenina y dihidrotricina, incorporadas, junto a la tricina, al polímero de lignina de am

Se conoce que los complejos quirales de Ag(I), Cu(I) o Cu(II) y Zn(II) catalizan eficazmente la cicloadición entre iluros de azometino generados a partir de iminoésteres y alquenos electrofílicos dando lugar a derivados heterocíclicos con elevadas enantioselectividades. Esta reacción suele funcionar con cantidades subestequiométricas tanto de base como de complejo quiral que actúa como ácido de Lewis, siendo impresionante el control de la reacción sobre los tres o los cuatro nuevos centros estereogénicos formados. De acuerdo con la experiencia previa del grupo de investigación en esta reacción 1,3-dipolar enantioselectiva, durante la elaboración de la siguiente memoria se estudiará la enantioselectividad de la cicloadición 1,3-dipolar de iluros de azometino y derivados alquénicos de la sacarina, en presencia de un ligando quiral constituido por diversos metales como Ag o Cu(II). Los derivados de isotiazol han demostrado tener una interesante actividad biológica, pues resultan ser precursores de sustancias que inhiben la acción de virus como el Sars-Cov2.

The Minisci reaction, which has been around for more than five decades, is still the preferred tool for the straightforward alkylation of basic heteroarenes. The recent developments in photocatalysis have opened novel pathways for radical generation under milder and more sustainable conditions. Implementing this approach into the Minisci reaction has renewed interest in this transformation, which is attractive per se in Medicinal Chemistry. Aspects such as sacrificial oxidants, catalysts, and specific reaction conditions should be carefully examined to evaluate the practicability of the protocol. This short review focuses on recent advances (2020 to February 2024) in photoinduced Minisci-type reactions, emphasizing sustainability. 1 Introduction 2 Using Noble-Metal-Based Photocatalysts 3 Noble-Metal-Free Methods Using Sacrificial Oxidants 4 Noble-Metal-Free Methods Without Sacrificial Oxidants 5 Conclusions and Perspectives.

En el siguiente trabajo se han estudiado los sistemas catalíticos heterogéneos llamados MOFs, del inglés Metal-Organic Frameworks, basados en 1,3-bis(carboximetil)imidazol (bcmim) haciendo uso de hierro y circonio como centros metálicos. Estas estructuras han sido preparadas mediante métodos simples y respetuosos con el medio ambiente y, posteriormente se ha testado su capacidad catalítica. Las estructuras de Zr-bcmim y Febcmim han sido estudiadas actuando como ácidos de Lewis en la esterificación de ácidos, relevantes sintética y biológicamente, con metanol (MeOH) y etanol (EtOH), llevándonos a la tranesterificación de aceites vegetales obteniendo rendimientos moderados. De esta misma manera la conversión de fructosa en ácido levulínico también ha sido evaluada obteniendo una selectividad total. Aunque se han observado ciertas interacciones de la estructura Fe-bcmim con los sustratos, se sigue trabajando en el desarrollo de un método de separación más eficiente.

Herein, silica-core shell magnetic nanoparticles were functionalized with imidazolium-based ionic liquid and 3-amino-1,2-propanediol, and the resulting hydrophilic media was used to stabilize bimetallic CoCu species. The structure of this new composite, Fe3O4@ILD-CoCu, was identified and analyzed by various techniques including TEM, XRD, XPS, VSM, FT-IR, EDX, and SEM Mapping. In the following, its catalytic performance was investigated in the reduction of nitrophenol compounds including 4-nitrophenol (4-NP), 3-nitrophenol (3-NP), and 2-nitrophenol (2-NP), decolorization of organic dyes such as methyl orange (MO), methyl red (MR), and rhodamine B (Rh B) and degradation of tetracycline and the results showed that the mentioned compounds participated properly in the reduction and degradation reactions. The research results showed that bimetallic cobalt-copper catalyst performs much better than monometallic cobalt and copper catalysts. The recyclability of the desired magnetic catalyst was also investigated and showed 14 runs of recyclability without a significant reduction in catalytic activity.

En el presente trabajo se lleva a cabo la síntesis de diferentes estructuras metal-orgánicas (MOFs) basados en cobre y paladio, y su uso como catalizadores en la reacción de acoplamiento cruzado Suzuki-Miyaura. Se pretende con el uso de catalizadores heterogéneos, por su mayor estabilidad, mejor separación y posibilidad de ser reciclables, realizar una metodología sostenible medioambientalmente siguiendo los principios de la química verde. De esta forma, se llevó a cabo la preparación de distintos MOFs, basados principalmente en cobre y 1,3-bis(carboximetil)imidazol. Posteriormente, estas estructuras se modificaron con diferentes sales de paladio. Estos materiales de cobre y paladio fueron utilizados como catalizadores en la reacción de acoplamiento cruzado con diferentes ácidos borónicos y cloruros de arilo, evaluándose la capacidad catalítica de los mismos. Para ello, previamente se llevó a cabo un estudio para obtener las condiciones óptimas de reacción mediante matrices de Taguchi con el objetivo de mejorar la eficiencia y rendimiento del proceso. Los sistemas catalíticos presentados permitieron llevar a cabo la reacción con buenos resultados.

The asymmetric catalytic synthesis of 1,2-diamines has received considerable interest, especially in the last ten years, due to their presence in biologically active compounds and their applications for the development of synthetic building blocks, chiral ligands and organocatalysts. Synthetic strategies based on C–N bond-forming reactions involve mainly (a) ring opening of aziridines and azabenzonorbornadienes, (b) hydroamination of allylic amines, (c) hydroamination of enamines and (d) diamination of olefins. In the case of C–C bond-forming reactions are included (a) the aza-Mannich reaction of imino esters, imino nitriles, azlactones, isocyano acetates, and isothiocyanates with imines, (b) the aza-Henry reaction of nitroalkanes with imines, (c) imine–imine coupling reactions, and (d) reductive coupling of enamines with imines, and (e) [3+2] cycloaddition with imines. C–H bond forming reactions include hydrogenation of C[double bond, length as m-dash]N bonds and C–H amination reactions. Other catalytic methods include desymmetrization reactions of meso-diamines.

Atenolol, one of the top five best-selling drugs in the world today used to treat angina and hypertension, and to reduce the risk of death after a heart attack, faces challenges in current synthetic methods to address inefficiencies and environmental concerns. The traditional synthesis of this drug involves a process that generates a large amount of waste and other by-products that need disposal. This study presents a one-pot DES-based sustainable protocol for synthesizing atenolol. The use of the DES allowed the entire process to be conducted with no need for additional bases or catalysts, in short reaction times, under mild conditions, and avoiding chromatographic purification. The overall yield of atenolol was 95%. The scalability of the process to gram-scale production was successfully demonstrated, emphasizing its potential in industrial applications. Finally, the ‘greenness’ evaluation, performed using the First Pass CHEM21 Metrics Toolkit, highlighted the superiority in terms of the atom economy, the reaction mass efficiency, and the overall process mass intensity of the DES-based synthesis compared with the already existing methods.

A novel magnetic nanocomposite modified with a new branched polymer containing nitrogen-rich ligand moieties was synthesized and used to stabilize Pd nanoparticles. The resulting catalyst was characterized by Fourier transform infrared spectroscopy, transmission electron microscopy, scanning electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, vibrating sample magnetometry, thermogravimetric analysis and energy-dispersive X-ray. The synthesized catalyst has been applied as an efficient catalyst in the reduction of nitro compounds to corresponding amines and reductive degradation of organic dyes such as methyl orange and methyl red. The catalyst showed high stability and reusability for 10 runs without significant loss in catalytic activity.

In this work, a convenient approach has been applied to discover the potential valorization of biomass waste such as orange peel in which PdCu-based nanostructured systems were synthesized via a one-step in-situ dry-milling approach to obtain the benign bimetallic catalysts with different palladium(Pd) and Copper(Cu) loadings on the orange peel support (Pd1%Cu1%, Pd0.3%Cu0.7%, Pd0.5%Cu0.5%, Pd0.5%Cu1%). Catalytic applications of these new composites were investigated in the Sonogashira-Hagihara coupling reaction as well as the Sonogashira–click reaction sequence to the preparation of substituted 4-aryl-1,2,3-triazoles and reduction of nitroaromatics under mild reaction conditions. Catalytic tests with the four activated carbons catalysts showed that the C@Pd1%Cu1% catalyst was the most active in the Sonogashira-Hagihara coupling reaction compared to the other catalysts. Also, the C@Pd0.5%Cu0.5% catalyst showed the highest catalytic activity in the reduction of 1-chloro-4-nitrobenzene and 4-nitrophenol in comparison with other prepared carbon catalysts.

The stereoselective synthesis of vicinal amino alcohols derivatives from 1-substituted cyclopropanols and chiral N-tert-butanesulfinyl imines is described. Cyclopropanols are easily prepared from carboxylic esters upon reaction with ethylmagnesium bromide in the presence of titanium tetraisopropoxide and undergo carbon–carbon bond cleavage by means of diethylzinc to produce, upon base deprotonation, enolized zinc homoenolates, which react with chiral sulfinyl imines in a highly regio- and stereoselective manner.

The Friedel-Crafts reaction is present in many fields of chemistry, being especially relevant in industrial applications, where is one of the key methodologies to transform raw materials into functionalized aromatic products. During the last few years, the industry has been compelled to modify conditions applied in their processes due to the demand for more environmentally conscious and secure production techniques. In this review, some alternatives to conventional solvents as the use of deep eutectic solvents (DESs) as new reaction media with compatible catalysts, commonly used in Friedel-Crafts reactions are reported. These new conditions represent a major step towards sustainability in comparison to traditional methods which employ stoichiometric amounts of Lewis acids and organic volatile solvents as reaction media.

The incidence of fractures and bone defects has been a significant driving force behind research efforts aimed at enhancing the quality of life for patients. However, it is important to acknowledge the inherent complexities of this research field. Where each patient could have different scenarios along with the difficulty of replicate the properties and complex design of the bones. In this study, scaffolds previously manufactured by different 3D printing techniques made of ceramic materials, specifically yttria-stabilised zirconia, which has excellent biocompatibility and mechanical properties, were used. These samples, which exhibit different designs to be employed in specific medical situation, have been characterised according to his morphology and porosity; using the outcomes for select the most promising for subsequent infiltration with appropriate biopolymers in order to improve their in vivo performance. Specifically oriented towards improve the osseointegration capacity by adding nanohydroxyapatite (nHA). The infiltrated samples were evaluated in terms of polymer degradation inside the composite, swelling evaluation, and studies of apatite formation capacity on the surface (bioactivity) assessed through XRD.

The demand for dental implants is increasing, although there is a wide variety of implants currently available in the market, it is necessary to implement improvements in their design and/or the selection of materials used. The development of biomimetic and bioactive Ti scaffolds for bone regeneration is necessary. In this context, this article proposes the design, manufacture and characterization of a porous titanium implant with the aim of eliminating some of the deficiencies found in commercially available titanium implants. Stress-shielding and the lack of osseointegration or bacterial infection are still some limitations to solve. Porous samples were produced using conventional Powder Metallurgy (PM) and the space holder (SH) technique. Ammonium bicarbonate particles were used as spacers in size ranges of 100–200 µm. The porosity and surface characterization were performed by Archimedes’ method and image analysis, while the mechanical behavior was analyzed by micro-mechanical testing. After that, the micromachining protocol of the implant is carried out. Substrates were chemically etched by immersion in fluorhydric acid at different times (15 s; 60 s and 125 s) to achieve a suitable surface roughness with biofunctional balance. Results showed that it is possible to obtain a desired longitudinal gradient. The optimized method described in this work suggests that it is a reasonable candidate for the development of dental implants with a good balance between reduced stress shielding and adequate mechanical strength.

STD NMR spectroscopy is a powerful ligand-observed NMR tool for screening and characterizing the interactions of small molecules and low molecular weight fragments with a given macromolecule, identifying the main intermolecular contacts in the bound state. It is also a powerful analytical technique for the accurate determination of protein–ligand dissociation constants (KD) of medium-to-weak affinity, of interest in the pharmaceutical industry. However, accurate KD determination and epitope mapping requires a long series of experiments at increasing saturation times to carry out a full analysis using the so-called STD NMR build-up curve approach and apply the “initial slopes approximation”. Here, we have developed a new protocol to bypass this important limitation, which allows us to obtain initial slopes by using just two saturation times and, hence, to very quickly determine precise protein–ligand dissociation constants by STD NMR.

A novel family of precision-engineered gene vectors with well-defined structures built on trehalose and trehalose-based macrocycles (cyclotrehalans) comprising linear or cyclic polyamine heads have been synthesized through procedures that exploit click chemistry reactions. The strategy was conceived to enable systematic structural variations and, at the same time, ensuring that enantiomerically pure vectors are obtained. Notably, changes in the molecular architecture translated into topological differences at the nanoscale upon co-assembly with plasmid DNA, especially regarding the presence of regions with short- or long-range internal order as observed by TEM. In vitro and in vivo experiments further evidenced a significant impact on cell and organ transfection selectivity. Altogether, the results highlight the potential of trehalose-polyamine/pDNA nanocomplex monoformulations to achieve targeting transfection without the need for any additional cell- or organ-sorting component.

Deep Eutectic Solvents (DESs) have appeared in recent years as an appealing alternative to classical organic solvents, due to their valuable environmental properties. In addition, these compounds, formed by the combination of one hydrogen bond donor with a hydrogen bond acceptor at a defined stoichiometric ratio, present other valuable activities not only as a reaction medium. DESs can also be employed as catalysts through hydrogen-bond interactions in different chemical transformations, thus substituting hazardous reagents and solvents. The search for novel and more environmentally friendly catalysts is an area of interest of pharmaceutical chemists, and therefore, the efforts made in the application of DESs as catalysts in the synthesis of APIs or its precursors are described, focusing mainly on condensations, nucleophilic additions to carbonyl moieties, and multicomponent reactions.

Performing abiotic synthetic transformations in live cell environments represents a new, promising approach to interrogate and manipulate biology and to uncover new types of biomedical tools. We now found that photocatalytic bond-forming reactions can be added to the toolbox of bioorthogonal synthetic chemistry. Specifically, we demonstrate that exogenous styryl aryl azides can be converted into indoles inside living mammalian cells under photocatalytic conditions.

Surfactants are ubiquitous in formulated products and technologies. As one of the most important commodity chemicals, their remarkable consumption leads to the necessity of finding sustainable alternatives. Although the use of renewable sources limits the available chemical space for a “Green” production, the great variety of naturally occurring precursors, i.e., fatty acids and sugars, opens a myriad of possibilities to create biosurfactants capable of replacing the fatigued fossil-derived amphiphiles. Here, we visit the concept of isomer-directed assembly applied to sugar-based surfactants, wherein amphiphile assembly and function are fine-tuned through changes in the stereochemical and regiochemical configuration of the molecule. As such, we show how isomerism defines directional interactions and solvation, ultimately dictating the assembly of surfactants. However, a general framework to understand the structure-function relationship for these is still missing, which is key to realizing this divergent set of tools for the design of new surfactants

233 p., Glycans are essential molecules that are ubiquitously found in every living cell. The interaction betweengalect in 4, a human sugar binding protein, with the histo blood group antigens has been studied by NuclearMagnetic Resonance ( Isothermal Titration Calorimetry and Molecular Dynamics simulations. Theeffect of the chemical modification of these antigens on the interaction with galectin 4 has been addressed.These antigens are mimicked by various pathogens, thus, the interaction between galectin 4 and theantigenic fragment of these pathogens ( LPS) has also been studied using NMR. Them ain co receptor for LPS, the glycoprotein CD14 has also been analysed. The relevance of each of theglycans of CD14 in its stability and folding, as well as for the interaction with galectin 4 has beencharacterized. Finally, using a solid phase synthesize r, the synthesis of oligosaccharides has beenperformed.

448 p., El trabajo de tesis tiene por objetivo generar materiales donde combinemos porosidad con otra propiedad fácilmente medible para generar sensores químicos. En este sentido los materiales con porosidad elevada son ideales porque habilitan una fuerte interacción entre las moléculas en disolución y el propio material. Sin embargo, incorporar una elevada porosidad en un sólido no es trivial y suelen requerir de un diseño sintético muy preciso. En este trabajo nos hemos centrado en dos tipos de materiales, los SMOFs (Supramolecularly assembled Metal-Organic Frameworks) y los MOGs (Metal-Organic Gels). Ambos difieren en la naturaleza de su posidad que se encuentra dentro del régimen microporoso (< 2 nm) para los SMOFs y en el régimen meso/macroporoso para los MOGs (> 2 nm). Por otro lado, la incorporación de una segunda propiedad como el magnetismo o la luminiscencia, requiere de constituyentes de estos materiales muy diferentes. Así, para disponer de propiedades magnéticas necesitamos de la incorporación de materiales con centros paramagnéticos, pero en el caso de las propiedades luminiscentes necesitamos de centros metálicos de capa completa para evitar el quencheado de la señal (si como es el caso trabajamos con metales de transición). Estos mismos materiales se han empleado como precursores de nanopartículas metálicos soportadas sobre una matriz carbonosa que funcionan como eficientes catalizadores de la termoreducción del CO2 con una alta selectividad hacia CO.Por lo tanto, se han generado dos familias de materiales, una primera basada en entidades [Cu6M(OH)6(adeninato)6(H2O)6]n+ (M: CoII, NiII, CuII, ZnII) que se ensamblan junto con anionesorgánicos (derivados de nucleobases y moléculas carboxílicas aromáticas, principalmente) para dar lugar a un material poroso (SMOF) con interesantes propiedades magnéticas que nos permiten cuantificar la cantidad de adsorbato incorporado por el material en disolución. La segunda familia basada en materiales metal-orgánicos de Zr(IV

288 p., El crecimiento económico de la sociedad cada vez tiene un mayor impacto en la degradación del medio ambiente, uno de los principales problemas para la humanidad. Este crecimiento conlleva un incremento en la producción y el consumo de recursos generando un incesante aumento de los contaminantes. Algunas de las evidencias más importantes de la contaminación se encuentran en el cambio climático promovido por las emisiones de gases de efecto invernadero y la degradación de recursos hídricos y suelos.En respuesta a esta problemática, en esta Tesis se ha abordado el desarrollo de materiales fotocatalíticos basados en titanio para la eliminación de contaminantes acuosos y la conversión de CO2, uno de los principales gases de efecto invernadero. La fotocatálisis se presenta como una atractiva tecnología verde. El funcionamiento de estos materiales se basa en la absorción de fotones de luz para llevar a cabo las reacciones químicas de oxidación y reducción. La fuente de radiación puede ser artificial o natural, siendo este uno de los puntos fuertes de este tipo de tecnología ya que puede funcionar con una fuente de energía natural como es la luz del sol. El método sol-gel proporciona una ruta de síntesis ydeposición muy versátil que, unido al concepto de las estructuras metal-orgánicas, ofrece un abanico de posibles modificaciones para la mejora de las propiedades de estos materiales buscando incrementar su actividad fotocatalítica.Se presenta en primer lugar una serie de recubrimientos fotocatalíticos de TiO2 poroso con un área superficial incrementada. La inmovilización del catalizador en forma de recubrimiento sobre un sustrato ha permitido la simplificación y mejora de un reactor microfluídico para la conversión de CO2 a metanol, respecto al enfoque común de los catalizadores soportados. Además, la cantidad de material utilizado en los recubrimientos fotocatalíticos es considerablemente inferior al de los soportados. Estos recubrimientos no solo poseen mayores rendimien

274 p., Glycans are ubiquitous in Nature. They are mainly found conjugated with other biomolecules giving rise to glycoproteins and glycolipids. Relevant biological events such as cell-cell, cell-matrix and host-pathogen interactions are orchestrated through the recognition of glycans by a group of specific proteins, called lectins. Several sub-families of lectins can be differentiated, being galectins, C-type lectins, and siglecs the most studied and suitable for biomedical applications.In this Thesis, different lectin-sugar systems have been selected and the fine details of their binding events have been decoded from the structural, conformational, and dynamic points of view. Particular attention to aspects such as conformational motions, multivalency, presentation, and the actual in-vitro or cell-like environment were the driving force behind this work.

A range of densely functionalized ullazines have been synthesized by a one-pot Rh(III)-catalyzed twofold C-H activation/oxidative annulation of N-arylpyrroles with alkynes. Electrophilic bromination at 5- or 5,7- positions of the EWG-substituted ullazine core offers an interesting single or double entry for further extended functionalization. Mechanistic considerations suggest two complementary paths, EWG-assisted and SEAr, for the C-H activations. All ullazines exhibit strong fluorescence emissions. Ullazines bearing thiophene and triarylamine units at 5- and 5,7- positions show a significant bathochromic shift in their emission spectra, attributed to the more extended electronic circuits present.

The ligand design factors that may influence the isolation of metallosupramolecular helicates or mesocates still deserve to be investigated. In this sense, dinuclear nickel(II), copper(II) and zinc(II) compounds were obtained by electrochemical synthesis using a family of five Schiff base ligands, H2Ln (n = 1–5), derived from bisphenylmethane and functionalized with bulky tert-butyl groups in the periphery and ethyl groups in the spacer. Six of the new complexes were characterized by X-ray crystallography, thus demonstrating that the helicate structure is predominant in the solid state. 1H NMR studies were performed for the zinc complexes to analyze if the helical architecture of the metal complexes is retained in solution. These studies reveal that the presence of a tert-butyl group in the ortho position with respect to the OH group is an essential factor identified for the existence of a helicate conformation in solution

The aim of the present research is to analyze thermophysical and tribological properties of PAO4 nanolubricants containing functionalized (GO-polyethyleneimine-oleic acid, GO-PEI-OA) and non-functionalized (GO) graphene oxide. Nanodispersions of these NPs were prepared, observing a better stability for the GO-PEI-OA nanolubricants. As for the tribological properties, significant improvements in coefficient of friction were obtained comparing with the base oil, being 28% for GO-PEI-OA (0.10 wt%). Concerning the anti-wear behavior, better results were obtained for GO-PEI-OA nanolubricants (0.15 wt%) with improvements of about 27%, 54% and 60% for the diameter, depth, and area of the wear track, respectively. Finally, Raman spectroscopy and surface roughness measurements were used to identify the tribological mechanisms of tribofilm formation and repairing.

Readily available N-carbamoyl indolines can be converted into highly valuable 2-alkenyl and 2-alkyl indoles in a one-pot reaction, through an autotandem catalytic cascade promoted by an iridium complex. The process entails a dehydrogenation reaction initiated by an iridium-promoted C(sp3)–H activation, the addition of the resulting indole to an alkyne -or alkene-partner, and a spontaneous loss of the carbamoyl directing group. Interestingly, the resulting C2-alkenyl indoles can participate in a variety of metal-catalyzed annulations initiated by C–H activation, including formal [4 + 1] and [4 + 2] cycloadditions, as well as cross-dehydrogenative cyclizations, thus enabling a divergent access to a collection of functionally rich nitrogen-containing heterocycles.

Functional inks for light-based 3D printing are actively being searched for being able to exploit all the potentialities of additive manufacturing. Herein, a fast visible-light photopolymerization process is showed of conductive PEDOT:PSS hydrogels. For this purpose, a new Type II photoinitiator system (PIS) based on riboflavin (Rf), triethanolamine (TEA), and poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) is investigated for the visible light photopolymerization of acrylic monomers. PEDOT:PSS has a dual role by accelerating the photoinitiation process and providing conductivity to the obtained hydrogels. Using this PIS, full monomer conversion is achieved in less than 2 min using visible light. First, the PIS mechanism is studied, proposing that electron transfer between the triplet excited state of the dye (3Rf*) and the amine (TEA) is catalyzed by PEDOT:PSS. Second, a series of poly(2-hydroxyethyl acrylate)/PEDOT:PSS hydrogels with different compositions are obtained by photopolymerization. The presence of PEDOT:PSS negatively influences the swelling properties of hydrogels, but significantly increases its mechanical modulus and electrical properties. The new PIS is also tested for 3D printing in a commercially available Digital Light Processing (DLP) 3D printer (405 nm wavelength), obtaining high resolution and 500 µm hole size conductive scaffolds.

We disclose a direct approach to the diastereoselective synthesis of phosphorus substituted N-acylaziridines based on a one-pot ZnCl2-catalyzed Joullié–Ugi three-component reaction of phosphorylated 2H-azirines, carboxylic acids and isocyanides. Hence, this robust protocol offers rapid access to an array of N-acylaziridines in moderate-to-good yields and up to 98:2 dr for substrates over a wide scope. The relevance of this synthetic methodology was achieved via a gram-scale reaction and the further derivatization of the nitrogen-containing three-membered heterocycle. The diastereo- and regioselective ring expansion of the obtained N-acylaziridines to oxazole derivatives was accomplished in the presence of BF3·OEt2 as an efficient Lewid acid catalyst.

La existencia de interacciones beneficiosas entre las bacterias presentes en el suelo y las plantas se conoce desde hace más de un siglo y está firmemente contrastada en diversos tipos de cultivos. Estas interacciones producen un beneficio para ambas partes ya que, al asociarse, las bacterias mejoran su crecimiento y desarrollo, a la vez que protegen a la planta frente a organismos patógenos del suelo. Aunque el ejemplo más conocido de asociación beneficiosa es la simbiosis entre las bacterias fijadoras de nitrógeno (rizobios) y las plantas leguminosas, actualmente se conocen otros microorganismos asociados a las plantas capaces de mejorar el crecimiento de las mismas. El término PGPR (Plant Growth-Promoting Rhizobacteria) se utiliza para referirse a microorganismos de vida libre que, al interaccionar con la planta bien de forma endófita o bien colonizando la raíz, favorecen el crecimiento de la misma. El efecto de las PGPR puede tener su origen en su acción como fertilizadores del suelo gracias a su capacidad para movilizar nutrientes, como productores de hormonas vegetales que modifican la fisiología de las plantas, como agentes protectores frente a diversos patógenos o por su capacidad para mejorar la respuesta de la planta al estrés al que está sometida en condiciones de sequía, exceso de salinidad o en suelos degradados. Uno de los mecanismos de acción de las PGPR es la modificación del balance hormonal de la planta de forma directa mediante la producción de auxinas (por ejemplo, el ácido 3- indolacético) y la modificación de los niveles de acetileno mediante la producción de ácido abscísico (ABA) y la eliminación de ácido 1-aminociclopropanocarboxílico (ACC), lo que permite una mayor protección frente a estrés abiótico, entre otros fenómenos. Un segundo mecanismo se basa en la adquisición de resistencia sistémica (SAR) en la planta, aumentando su capacidad de defensa frente a organismos patógenos. En este último caso, hay dos posibles canales de actuación: uno

Being aware of the need to develop more efficient therapies against cancer, herein we disclose an innovative approach for the design of selective antiproliferative agents. We have accomplished the conjugation of a coumarin fragment with lipophilic cations (triphenylphosphonium salts, guanidinium) for providing mitochondriotropic agents that simultaneously target also carbonic anhydrases IX and XII, involved in the development and progression of cancer. The new compounds prepared herein turned out to be strong inhibitors of carbonic anhydrases IX and XII of human origin (low-to-mid nM range), also endowed with high selectivity, exhibiting negligible activity towards cytosolic CA isoforms. Key interactions with the enzyme were analysed using docking and molecular dynamics simulations. Regarding their in vitro antiproliferative activities, an increase of the tether length connecting both pharmacophores led to a clear improvement in potency, reaching the submicromolar range for the lead compounds, and an outstanding selectivity towards tumour cell lines (S.I. up to >357). Cytotoxic effects were also analysed on MDR cell lines under hypoxic and normoxic conditions. Chemoresistance exhibited by phosphonium salts, and not by guanidines, against MDR cells was based on the fact that the former were found to be substrates of P-glycoprotein (P-gp), the pump responsible for extruding foreign chemicals; this situation was reversed by administrating tariquidar, a third generation P-gp inhibitor. Moreover, phosphonium salts provoked a profound depolarization of mitochondria membranes from tumour cells, thus probably compromising their oxidative metabolism. To gain insight into the mode of action of title compounds, continuous live cell microscopy was employed; interestingly, this technique revealed two different antiproliferative mechanisms for both families of mitocans. Whereas phosphonium salts had a cytostatic effect, blocking cell division, guanidines led to cell death via apo

Amides are ubiquitous in natural and synthetic compounds, and amidation is by far the most prevalent reaction in medicinal chemistry. In addition, atom-economical procedures for the direct amidation of esters or acids with amines are in high demand. Encouraged by the abundance and low toxicity of iron compounds, we envisaged that a new iron-catalyzed protocol for the acylation of amines with both esters and carboxylic acids could be designed if the iron catalyst was combined with dioxygen. Several experiments were carried out in order to define the iron source and to evaluate the effect of molecular oxygen, additives and different reaction media. A number of substrates were then reacted under optimized conditions, and experimental studies (kinetic, radical trapping and electron paramagnetic resonance experiments) were conducted to shed light on the reaction mechanism. As a result, a new use for dioxygen as an inducer of the direct amidation between amines and carboxylic acids or esters has been found. Thus, an earth-abundant first-row metal catalyst (Fe(acac)3) at low loading combined with pivalic acid and molecular oxygen at atmospheric pressure triggers the reaction in a biodegradable greener solvent such as diethyl carbonate. More than 65 high-yielding examples prove the generality of the procedure, which also resulted to be scalable. In addition, insight into the mechanism behind this reaction taking place under oxygenated conditions is provided as well as an explanation for the results obtained in the absence of dioxygen.

This work explores the biological evaluation of novel cyanomethyl vinyl ether derivatives as antiproliferative agents. Tubulin, crucial to microtubule structure and function, is a target for cancer therapies. In vitro cytotoxicity assessments revealed significant activity in SKOV3 ovarian carcinoma cells and A549 lung carcinoma cells. Structure-Activity Relationship (SAR) analysis indicated that the E isomer and specific substitutions influenced the biological activity. Computational assays predicted favorable ADME properties, highlighting potential as anticancerous agents. Molecular docking studies demonstrated that compound 12E, with the E geometry of the double bond and fused polyaromatic rings such as phenanthrene, has robust interaction with tubulin, suggesting enhanced stability due to diverse amino acid interactions. Comparative spatial distributions with colchicine further indicated potential mechanistic similarities.

Surface modifications play a crucial role in enhancing the functionality of biomaterials. Different approaches can be followed in order to achieve the bioconjugation of drugs and biological compounds onto polymer surfaces. In this study, we focused on the immobilization of an amoxicillin antibiotic onto the surface of poly-L-lactic acid (PLLA) using a copper-free amino-yne click reaction. The utilization of this reaction allowed for a selective and efficient bioconjugation of the amoxicillin moiety onto the PLLA surface, avoiding copper-related concerns and ensuring biocompatibility. The process involved sequential steps that included surface activation via alkaline hydrolysis followed by an amidation reaction with ethylendiamine, functionalization with propiolic groups, and subsequent conjugation with amoxicillin via a click chemistry approach. Previous amoxicillin immobilization using tryptophan and fluorescent amino acid conjugation was carried out in order to determine the efficacy of the proposed methodology. Characterization techniques such as X-ray photoelectron spectroscopy (XPS), Attenuated Total Reflection (ATR)–Fourier Transform Infrared (FTIR) spectroscopy, surface imaging, water contact angle determination, and spectroscopic analysis confirmed the successful immobilization of both tryptophan and amoxicillin while maintaining the integrity of the PLLA surface. This tailored modification not only exhibited a novel method for surface functionalization but also opens avenues for developing antimicrobial biomaterials with improved drug-loading capacity.