El CRAI romandrà tancat del 24 de desembre de 2025 al 6 de gener de 2026. La validació de documents es reprendrà a partir del 7 de gener de 2026.
El CRAI permanecerá cerrado del 24 de diciembre de 2025 al 6 de enero de 2026. La validación de documentos se reanudará a partir del 7 de enero de 2026.
From 2025-12-24 to 2026-01-06, the CRAI remain closed and the documents will be validated from 2026-01-07.
 

Tesis Doctorals - Departament - Química Inorgànica i Orgànica

URI permanent per a aquesta col·leccióhttps://hdl.handle.net/2445/101203

 Estadístiques

Examinar

Enviaments recents

Mostrant 1 - 20 de 96
  • Miniatura
    Tesi
    Development of Novel Carbazole- and Dibenzothiophene-based Organic Semiconductors and its application in Organic Field-Effect Transistors
    (Universitat de Barcelona, 2025-12-10) Fabregat Pallejà, Clara; Velasco Castrillo, Dolores; Garcia Amorós, Jaume; Universitat de Barcelona. Departament de Química Inorgànica i Orgànica
    [eng] In recent decades, electronic devices have become indispensable and have been subtly woven into the fabric of society. The growing demand for more advanced technologies requires the development of new semiconductors, which are the foundation of modern electronics. Although inorganics such as silicon and germanium maintain a dominant role, they have intrinsic limitations that organic semiconductors (OSCs) can overcome, thanks to their structural modulability and compatibility with flexible and lightweight substrates. The performance of these devices depends on both the molecular properties (energy levels, packaging) and the processing conditions, which determine their morphology and crystallinity. In this context, the thesis studies semiconductors based on carbazole and dibenzothiophene (DBT) for organic field-effect transistors (OFETs) with the aim of correlating the molecular structure with the performance of devices and advancing the development of next-generation organic electronics. The triindole, derived from carbazole, was first investigated for its high potential as a hole transporter. N-alkylation allowed triindole derivatives to be obtained with chains from C2 to C12, subsequently being integrated into OFETs with various deposition architectures and techniques. For short chains, the resulting films were disordered, while substitution with hexyls proved to be optimal, with mobilities greater than 3 × 10⁻³ cm² V⁻¹ s⁻¹ in both vacuum evaporated and solution-processed devices. The deposition technique was decisive: vacuum evaporation favored medium chains, while bar-assisted meniscus shearing (BAMS) allowed operation with long chains, showing the complementarity between the two methods. Subsequently, peripheral alkyl substitution was introduced at the para and meta positions with respect to nitrogen. The substituted para-methyl triindole stood out as the best semiconductor, with mobilities of up to 4.7 × 10⁻³ cm² V⁻¹ s⁻¹. Otherwise, the lengthening of the chains or the substitution in the target position reduced mobility and gave rise to rougher morphologies and irregular crystalline domains. Beyond alkylation, triindoles and indolocarbazoles were functionalized with azobenzene (AB) chromophores to develop photoresponsive OFETs. Both the anchor position (No C-) and the number of AB units were varied. Time-of-flight measurements confirmed p-type behavior in AB-triindoles, with mobilities of up to 1.5 × 10⁻⁴ cm² V⁻¹ s⁻¹. However, additional AB units altered π–π stacking and reduced transport. AB-indolocarbazoles suffered from low solubility and deficient films, which made their manufacture difficult. Although the integration of these compounds is still preliminary, the results pave the way for the future development of photomodular OFETs. The last part of the thesis focused on the π extension of DBT derivatives through simple functionalizations, obtaining compounds with improved transport or emissive properties. All showed p-type behaviour, with mobilities of up to 8.3 × 10⁻⁵ cm² V⁻¹ s⁻¹. π extension and stiffening by cycle closure unlocked phosphorescence at room temperature (RTP) in Zeonex matrices, attributed to the reduction of singlet-triplet separation that facilitates crossover between systems. Functionalization modulated the balance of properties: phenanthre units favored mobility, while benzothiophene substituents enhanced RTP, with quantum yields of up to 14%. In some derivatives, the combination of RTP and intense blue fluorescence produced white light emission. Overall, the thesis shows how a precise molecular design, whether by alkylation, chromophore integration or π extension, directly governs the packaging, morphology, charge transport and emissive behavior of CSOs. By linking molecular design with device engineering, this work provides fundamental knowledge and practical guidelines to improve the performance and functionality of OFETs, paving the way towards flexible, economical and multifunctional organic devices. .
  • Miniatura
    Tesi
    New visible-light activated caging groups based on COUPY dyes for anticancer phototherapeutic applications
    (Universitat de Barcelona, 2025-10-10) López Corrales, Marta; Marchán Sancho, Vicente; Universitat de Barcelona. Departament de Química Inorgànica i Orgànica
    [eng] This doctoral thesis has addressed the study of several therapeutic applications against cancer of a new family of photolabile protective groups (PPGs) based on COUPY coumarins, photoactivated with visible light. First, the effect of introducing a methyl group in a position adjacent to the photolabile bond in the coumarin skeleton was investigated, to evaluate how the formation of a secondary carbocationic intermediate influences the efficiency of the photolysis process. The sequential deprotection of two coumarin-protected functionalities within the same reaction medium was successfully achieved by stepped irradiation using visible light compatible with biological systems. This was carried out first by irradiating with red light to selectively deprotect the coumarin-based PPG COUPY, followed by irradiation with green light to activate the dicyanocoumarin-based PPG. The impact of replacing the pyridine group with a pyrimidine group was also studied, as well as the effect of modifying the outgoing group. The mitochondrial accumulation of COUPY photolabile compounds was confirmed by confocal microscopy in HeLa cells, thus demonstrating that the photoactivation of protected derivatives of 2,4-dinitrophenol takes place specifically in this organelle. Subsequently, the replacement of the methyl group by a phenyl group was explored as a strategy to further stabilize the carbocationic intermediate and improve the efficiency of the photodeprotection process, resulting in COUPY and dicyanocoumarin derivatives with slightly faster photolysis. Secondly, the ability of COUPY coumarin-based PPGs to release biologically active compounds into the mitochondrion was investigated. Specifically, the derivatives of the antitumor agents chlorambucil (CLB) and 4-phenylbutyric acid (4-PBA) showed remarkable phototoxicity in cancer cells after irradiation with green-yellow light, with IC50 values in the nanomolar range. This effect is attributed to a synergy between the release of the drug and the generation of reactive oxygen species (ROS) by coumarin. These results highlight the potential of COUPY coumarin-based PPGs as anticancer agents combining photodynamic therapy (PDT) and photoactivated chemotherapy (PACT). Finally, taking advantage of their activation with visible light, the COUPY derivatives were functionalized with 2,2'-bipyridine, which allowed their incorporation into polypyridyl Ru(II) complexes. Two Ru-COUPPY complexes were synthesized, capable of releasing the antitumor drugs CLB and 4-PBA both under irradiation with green-yellow light and red light in a few minutes with improved photoefficiency compared to PPGs based on COUPY coumarins. Ru-COUBPY complexes show outstanding photocytotoxic activity against CT-26 cancer cells, both under normoxia and hypoxia conditions, with efficacy in the nanomolar range. In addition, they have excellent stability in the dark in culture medium, as well as a high photostability of the resulting photoproduct, which makes them very promising candidates for applications in next-generation anticancer photodynamic therapies. These Ru-coumarin complexes act as dual anticancer agents: they generate reactive oxygen species (ROS) via PDT and, simultaneously, release antitumor drugs through PACT. Therefore, Ru-COUBPY complexes that can be activated with red light represent an innovative and effective alternative to conventional cancer therapies.
  • Miniatura
    logoOpenAccessTesi
    Metal catalysed asymmetric C–C bond forming reactions
    (Universitat de Barcelona, 2024-12-12) Galeote Martin, Oriol; Urpí Tubella, Fèlix; Romea, Pedro; Universitat de Barcelona. Departament de Química Inorgànica i Orgànica
    [eng] This thesis presents novel methodologies for asymmetric C–C bond forming reactions, focusing on catalytic approaches involving chiral nickel(II) complexes. Chapter I introduces a new approach to direct asymmetric aldol reactions using thioimides. A new method was successfully developed to obtain TIPS-protected anti-aldol adducts with exceptional stereocontrol, achieving high diastereoselectivities (ca 80:20) and enantioselectivities up to 99% ee, using the chiral complex [(R)- Tol-BINAP]NiCl2 as the catalyst. This approach was applied to a wide range of substrates, which demonstrated the robustness of this method. Moreover, preliminary studies with cobalt and iron complexes suggest that these metals could offer promising alternatives for future development of sustainable catalytic systems. The thesis also explores the reactivity of propargyl aldehydes, though background processes without sufficient stereochemical control hindered successful outcomes. Additionally, the acetate aldol reactions, known to be specially challenging substrates compared to the propionate counterparts, was optimized. Unfortunately, all catalysts attempted yielded poor enantioselectivities, which forced us to discard this approach. In addition, efforts with α,β-unsaturated aldehydes struggled with regioselectivity, though it was found that using less sterically demanding Lewis acids, such as TMSOTf, favoured the 1,2 addition pathway. A special case of α,β-unsaturated aldehyde, propargyl aldehyde, was protected with a cobalt complex. This approach however presented several challenges associated with a background reaction, which eroded the enantioselectivity significantly and could not be resolved. A significant achievement of this research was found in Chapter II. It consisted in the development of a novel asymmetric Michael addition to α,β-unsaturated aldehydes catalysed by chiral nickel(II) complexes. This method enables access to all possible stereocenters through the modification of the chiral ligand, showing excellent regioselectivity, with most substrates exhibiting a regioselectivity ratio (1,2:1,4) of over 1:99. The method proved robust in terms of enantioselectivity, consistently yielding enantiopure compounds (99% ee) in a wide range of substrates. The [(R)-DTBM-SEGPHOS]NiCl2 complex was identified as the most effective for producing syn Michael adducts with high diastereoselectivity, though limitations arose with electron- poor substrates and steric hindrance at the Cα position. On the other hand, [(R)-BINAP]NiCl2 furnished the complementary anti counterparts, and it has demonstrated broader substrate tolerance, although slight losses in diastereoselectivity were noted with electron-rich substrates. The resultant Michael adducts provide valuable enantiomerically pure intermediates, which can be converted into various functional groups, such as esters, amides, alcohols, or aldehydes as demonstrated in Chapter III. A novel reaction was also developed to synthesize chiral lactones in high yields. Additionally, this methodology was applied to the synthesis of the commercial opioid (R,R)- tapentadol, achieving both stereocenters with high control. The six-step synthesis sequence yielded 45% overall, utilizing commercially available reagents and requiring only two chromatographic purification steps, thus offering a scalable and efficient process. Chapter IV shifts focus to the development of new methods for producing β-amino carbonyl compounds. Direct asymmetric Mannich additions of thioimides to activated imines were attempted but without success, due to the instability of imines and their tendency to promote the formation of undesired silyl ketene acetals of thioimides. Afterwards, N,O- and N,N-aminals were used as imine surrogates. Despite poor results with most of these substrates, N,N-dibenzylaminal arised as a promising substrates for Mannich additions. Finally, a stereodivergent approach using 1,3-dipolar cycloadditions of nitrones yielded excellent results. The nitrone addition to N-acryl thioimides, catalysed by either [(R)-DTBM- SEGPHOS]NiCl2 or [(S)-BINAP]NiCl2, produced cycloaddition products with endo and exo selectivity, respectively. This opens avenues for further development of highly stereocontrolled carbon-carbon bond-forming reactions from thioimides, driven by chiral nickel(II) complexes. The research offers valuable insights and lays the groundwork for future advancements in asymmetric catalysis and stereoselective synthesis.
  • Miniatura
    logoOpenAccessTesi
    Síntesis total de la Anfidinolida B1
    (Universitat de Barcelona, 2025-03-07) Barnils Rodríguez-González, Cristian; Costa i Arnau, Anna M.; Vilarrasa i Llorens, Jaume; Universitat de Barcelona. Departament de Química Inorgànica i Orgànica
    [spa] En esta Tesis Doctoral se ha estudiado la síntesis total de la Anfidinolida B1, un macrociclo de 26 miembros aislado por primera vez por Shimizu y colaboradores en 1994 en Santo Tomás, una de las Islas Vírgenes de los Estados Unidos de América. La molécula es citotóxica a nivel nM. La retrosíntesis diseñada en el grupo desconecta la molécula en cuatro fragmentos de complejidad similar. La síntesis de cada fragmento se resume a continuación. Fragmento I. Se han optimizado diferentes caminos sintéticos para llegar a la (E)-3-metil-4-yodo-3-buten-2-ona (1), un intermedio clave para la síntesis del Fragmento I. En primer lugar, se llevó a cabo la alquilación con yodoformo a partir del metilalonato de dietil, transformación que ya se había empleado anteriormente en nuestro grupo de investigación. Después de obtener 1 a escala multigram, se procedió en esta Tesis a la alilación enantioselectiva de este intermedio, llegando al alcohol terciario deseado con buen rendimiento y exceso enantiomérico. Finalmente, se protegió al grupo hidroxilo como éter de terco-butildimetilsilil de manera cuantitativa. Así pues, se pudo sintetizar satisfactoriamente el Fragmento I de la Anfidinolida B1 a escala multigram. Con la finalidad de encontrar una alternativa más rápida y eficiente, también se ha estudiado una ruta sintética conocida que parte del metacrilato de metilo. Esta ruta transcurre en cinco etapas cortas y con rendimiento cuantitativo hasta llegar a 1. Por lo tanto, se puede concluir que es una ruta excelente porque, aunque tiene una etapa más que la que partía del malonato de dietil, desarrollada por el Dr. Cascales, las reacciones son más cortas y los reactivos más baratos. También se ha ensayado una nueva ruta, propuesta en nuestro grupo, que parte de la 3-metilbut-3-en-2-ona. Aunque las etapas de eliminación y de transhalogenación tienen rendimientos menores a los esperados, nos permite llegar al precursor 1 en solo tres pasos (y los dos primeros pueden realizarse "one pot"). Por lo tanto, esta vía nos permite reducir a la mitad el número de etapas, usando reactivos económicos. Fragmento II En el capítulo 3 se describe la síntesis de una nueva versión del Fragmento II. Los estudios realizados con anterioridad en nuestro grupo demostraron que la vinilo cetona presente en este fragmento era demasiado lábil. Por ello, decidimos preparar la propenil cetona correspondiente, que debería ser menos propensa al ataque de nucleófilos. El nuevo Fragmento II se preparó siguiendo la retrosíntesis diseñada anteriormente. También se optimizaron algunos pasos, como la formación del doble enlace, que se llevó a cabo con rendimientos excelentes siguiendo el método de Ando. Así pues, vamos a preparar el Fragmento II en 11 etapas y un 7% de rendimiento a partir del (S)-lactato de metilo. También vamos a estudiar otra nueva ruta sintética propuesta en la Tesis del Dr. Cascales, pero no culminada por él. En ésta, se empleó pseudoefedrina como auxiliar quiral (Myers et al.), en concreto (1R,2R)-pseudoefedrina, que fue acilada con anhídrido propanoico. Después se generó in situ el enolado correspondiente con LDA, que reaccionó con (R)-óxido de propileno. Una vez obtenido el producto deseado, se eliminó el auxiliar quiral por tratamiento con ácido sulfúrico en agua y dioxano, obteniendo así la correspondiente lactona. Así, en sólo tres etapas se llegó al epímero en C4 de la lactona antes preparada, que tiene un centro estereogénico con la configuración inversa a la del producto natural. Más adelante habrá que invertir este estereocentro, por ejemplo, formando el éster mediante una reacción de Mitsunobu. A partir de ahí, se siguió un camino nuevo, no investigado en la Tesis antes mencionada, que consiste en reducir la lactona al correspondiente lactol con DIBALH y realizar in situ la olefinación del lactol con un iluro de tributilfosfonio, consiguiendo el producto deseado como un único diastereómero y con un rendimiento excelente. Una vez obtenida la olefina deseada, se realizó una dihidroxilación de Sharpless. El diol formado se protegió en forma de cetal isopropilidénico. Después se transformó el éster en la correspondiente medición de Weinreb, que se hizo reaccionar con el bromuro de 1-propenilmagnesis para dar el Fragmento II, pero con la configuración inversa, en C25-OH, a la del producto natural. De esta manera hemos completado la segunda vía o aproximación al Fragmento II, que requiere una reacción de inversión adicional. Habrá que realizar esta inversión (de la configuración de C25-OH) y después proceder a la esterificación con el resto del esqueleto. Este segundo camino implica un total de 9 etapas, con un rendimiento global del 13%. Fragmento III. Se ha completado la síntesis del Fragmento III, en 9 etapas a partir del auxiliar de Evans, con un rendimiento global del 15%. Como mejoras respecto a síntesis anteriores del Fragmento III, se ha conseguido optimizar la reacción de alquilación (alilación con 2,3-dibromopropeno) del auxiliar de Evans acilado, con un rendimiento reproducible ≥ 78%. También se ha optimizado la etapa de hidrólisis de la acil-oxazolidinona, con borohidruro de sodio concentrado en agua, obteniendo un rendimiento ≥ 85%. Se ha preparado el Fragmento III "alargado", para evitar un segundo acoplamiento de Negishi. Fragmento IV. Este Fragmento se preparó a partir del 1,4-butandiol en seis etapas y con un 46% de rendimiento. Unión de Fragmentos. Con la finalidad de llegar a la Anfidinolida B1, se realizó en primer lugar la unión del Fragmento I con el Fragmento III "alargado", mediante un acoplamiento de Negishi. Posteriormente, la desprotección del hidroxilo primario, seguida de una oxidación permitió obtener el alcohol correspondiente. Este se unió con el Fragmento IV mediante una olefinación de Julia–Kocienski. Finalmente, la cadena carbonada de la Anfidinolida B1 se completó mediante la formación del éster con el Fragmento II, vía una reacción de Shiina. Desgraciadamente, sólo se llegó a un total de 6 mg del intermedio acíclico deseado (el precursor sobre el que, en forma de C16-OH o como C16-OTBS, esperábamos efectuar una RCM). En la práctica, para llegar a obtener 6 mg del precursor de la reacción de ring-closing metathesis se requirieron 38 etapas totales con un rendimiento global del ~3% (longest linear sequence, 15 etapas). No disponemos en nuestro laboratorio de cantidades suficientes de todos los intermedios sintéticos —de los cuatro fragmentos— para repetir las últimas operaciones y para optimizar de nuevo la reacción de esterificación de Shiina.
  • Miniatura
    Tesi
    Heterobifunctional molecules: PROTACs and beyond
    (Universitat de Barcelona, 2025-04-11) Rafael Miguel, Sergi; Riera i Escalé, Antoni; Mayor‐Ruiz, Cristina; Universitat de Barcelona. Departament de Química Inorgànica i Orgànica
    [eng] Our body is an intricate, well-organized structure formed by trillions of cells. Each one of these cells is a highly complex entity composed of thousands of biomolecules that enable it to carry out its functions. Among them, proteins stand out as the machinery that orchestrates most cellular processes. Alterations in normal protein activity will lead to cellular malfunction and the appearance of diseases. For this reason, protein modification by small molecules has stood as the main pharmacological approach. However, the traditional occupancy-based mechanism of action of most drugs falls short at targeting the wide range of the human proteome. 80% of the disease associated proteins remain undruggable, mainly due to the lack of well-defined pockets in the protein. Recently, new technologies are being developed to overcome the limitations of this mechanism. One of the most promising is the use of Proteolysis Targeting Chimeras (PROTACs). PROTACs work by hijacking the endogenous protein homeostasis system to induce the degradation of the target protein. Their event-based mechanism of action allows PROTACs to bypass the need for high-binding affinities with the target protein, whilst maintaining high selectivity. Together with other advantages like a catalytic mechanism, more permanent effect, lower dosing and less appearance of resistance, puts PROTACs as the most promising alternative to traditional drugs. This doctoral thesis explores PROTAC’s design and synthesis process, as well as the following challenges that the field is facing. In Chapter 2, we explored the use of PROTACs in Castrate Resistant Prostate Cancer (CRPC). This disease comprises 10-20% of Prostate Cancer patients, and most of these cases arise from the appearance of an Androgen Receptor (AR) alternative splice variant that lacks the ligand binding domain (AR-V7). AR-V7 cannot be drugged efficiently due to the intrinsically disordered nature of its structure, leading to high mortality rates. We envisioned the use of PROTACs as a promising alternative to target this challenging protein. Its design is based on the CAM family of ligands, previously reported in the group, to recruit AR-V7. In Chapter 3, we focused on the resistance mechanisms to degraders. Previous work done by Winter’s group in 2019 highlighted that resistance arises away from the target protein. Namely, UBE2Mmut cells become pan-resistant to all degraders. Using this cellular model, we started a high throughput screening campaign followed by an SAR to identify its synthetic vulnerabilities. This study led to the disclosure of RBS-10; a small-molecule capable of differentially kill UBE2Mmut cells. Further work on its mechanism of action led to uncovering that RBS-10 is a prodrug bioactivated by NQO1, which generates metabolites that induce ROS and DNA damage. Chapter 4 showcases the ability of proximity-inducing pharmacology to modulate protein activity. We envisioned the use of heterobifunctional molecules to target the ETS2 Repressor Factor (ERF), an attractive oncogenic target that has traditionally remained undruggable. Through a high- throughput screening of an electrophilic library we identified a first-in-class covalent binder of ERF. After characterizing its binding, we designed and synthesized different bifunctional molecules to modulate ERF’s activity. On one hand, we prepared PROTACs to induce its degradation, inducing cell proliferation and differentiation. On the other hand, we worked on Phosphatase Recruiting Chimeras (PhoRCs), able to induce its dephosphorylation by proximity with a phosphatase. These molecules over-activate ERF, hijacking the cell in a non-proliferative state and acting as a tumor suppressor. Finally, we also worked on the development of Relocalization Targeting Chimeras (ReloTACs), which induce the nuclear localization of ERF through the formation of a ternary complex with a nuclear protein, p300. In summary, the work in this doctoral thesis highlights the advantages that PROTACs and proximity-inducing approaches have over traditional pharmacology. It emphasizes both their ability to target previously considered undruggable proteins, as well as their design and synthesis process. Furthermore, it displays their vast potential to modulate protein activity and develop novel therapies.
  • Miniatura
    Tesi
    Peptide-based approaches for the race against resistant bacteria
    (Universitat de Barcelona, 2024-12-05) Garcia Gros, Júlia; Rabanal Anglada, Francesc; Cajal Visa, Yolanda; Universitat de Barcelona. Departament de Química Inorgànica i Orgànica
    [eng] Antimicrobial resistance to almost all available antibiotics is on the top ten list of global public health challenges of the World Health Organization. Each year, the deaths due to AMR infections achieve the alarming numbers of 35000 in the European Economic Area (EEA) and 700000 worldwide. This problem is due to the high capacity of bacteria to multiply and mutate quickly, caused mainly by the indiscriminate use of broad-spectrum antibiotics or the excessive use of antibiotics in the veterinary and food industries. The development of new antibiotics with novel mechanisms of action faces significant challenges, both scientifically and economically. As a result, the number of antibiotics approved by the Food and Drug Administration or the European Medicines Agency has drastically decreased in recent years. This thesis presents the design, synthesis, characterization and evaluation of the in vitro activity of 18 analogues of polymyxin B and 9 analogues of murepavadin, two cyclic antimicrobial peptides. The analogues incorporate a disulfide bond in the macrocycle, aimed at maintaining the in vitro activity against bacteria, while facilitating peptide proteolysis compared to an amide bond, potentially reducing renal toxicity. The analogues have been synthesized by solid-phase peptide synthesis (SPPS) following an Fmoc/tBu protection scheme. In addition, the mode of action of two polymyxin analogues has been studied using model membranes and biophysical techniques. Finally, polymyxin B and murepavadin have also been combined with cyclodextrins, and the formation of inclusion complexes has been studied by ITC, DSC, TGA, MS, UV-Vis and NMR techniques.
  • Miniatura
    logoOpenAccessTesi
    Simulations of glycoside hydrolase and phosphorylase reaction mechanism: families GH20, GH29, GH129 and GH130
    (Universitat de Barcelona, 2024-12-04) Cuxart Sanchez, Irene; Rovira i Virgili, Carme; Universitat de Barcelona. Departament de Química Inorgànica i Orgànica
    [eng] The most abundant family of biomolecules on earth are carbohydrates. Also known as glycans, sugars or saccharides, are based on polyhydroxycarbonyl backbones with a vast array of chemical and structural modifications, which confer them different physico-chemical properties. They participate in many biological processes related to structural, energy storage and molecular signaling functions, and the many possibilities regarding structure and function of carbohydrates open questions in the field of glycobiology. The simplest form of carbohydrates, monosaccharides, assemble through glycosidic bonds to form larger structures (oligo- or polysaccharides) or glycoconjugates in combination with other families of biomolecules (like glycoproteins). Carbohydrates are flexible: from the atomic positions of the atoms forming a monosaccharide ring, to the rotation of the linkages between sugar units, it is a property that confers them the possibility to arrange their atoms in different positions resulting in different conformations, a key aspect in processes where they take part in. Carbohydrates undergo chemical changes in the form of degradation, synthesis and modifications in the several biological processes where they participate. Operating these reactions, we find the Carbohydrate Active Enzymes (CAZYmes), whose functions are increasingly being discovered. The study of CAZYmes has attracted research attention, as it opens windows in how complex metabolic pathways protagonized by carbohydrates work and paves new paths for medical, biotechnological and environmental applications. In this dissertation we uncover the catalytic mechanisms of four enzymes involved in the breakdown of saccharide chains: three via hydrolysis of glycosidic bonds, known as glycoside hydrolases (GHs), and one via sugar phosphorylation (glycoside phosphorylases or GPs), respectively. With computer simulations based in all-atoms models, combining QM/MM approaches with enhanced sampling methods, we simulate the chemical transformations that diverse saccharides undergo in the active site of the enzymes, including their conformational itineraries. The study of enzyme catalysis is an interdisciplinary field, where different techniques from structural biology to biochemistry give insights on their structure and function. Computational techniques such as molecular dynamics, give the opportunity to characterize at the atomic and molecular level states that would be otherwise difficult to capture with experimental methods, such as the short-lived transition states or the sometimes elusive native enzyme-substrate complexes. In this Thesis we aim to uncover the catalytic mechanisms of enzymes relevant for medical and biotechnological applications that have some particularity that sets them apart from other well-established GH mechanisms. This Thesis dissertation contains the following chapters: Chapter 1 - Introduction. Contextualization of the general topics covered in this dissertation, description of the scope of this Thesis and listing of the specific objectives. Chapter 2 - Methods. Section outlining the main theoretical basis of the computational techniques applied and a description of the general workflow used in this work. Chapter 3 - The catalytic mechanism of GH20 lacto-N-biosidase. We uncover the catalytic mechanism of the enzyme LnbB, involved in the degradation of human milk oligosaccharides, which 2 uses the substrate for the nucleophilic role of catalysis. Chapter 4 - The catalytic mechanism of GH130 N-glycan mannoside phosphorylase. We elucidate the catalytic mechanism of the enzyme UhgbMP, which incorporates phosphate to mannosyl substrates via a mechanism involving the substrate in a double proton transfer. Chapter 5 - The catalytic mechanism of GH129 3,6-anhydro-D-galactosidase. We characterize the catalytic mechanism of bacterial ZgGH129, which degrades the unique algal 3,6-anhydro-D-galactosidase-based carrageenan oligosaccharides via an unusual conformational itinerary. Chapter 6- Substrate recognition and catalytic mechanism of human GH29 fucosidase. We elucidate the first reaction step of the reaction mechanism of the enzyme FucA1, recognizes and degrades fucosylated glycans, and unveil structural and dynamic details of its recognition of fucosylated motifs.
  • Miniatura
    logoOpenAccessTesi
    Exploiting heterometallic lanthanide complexes for technological applications: Quantum Computing, Optical Properties and Magnetic Refrigeration
    (Universitat de Barcelona, 2024-11-29) Maniaki, Diamantoula; Aromí Bedmar, Guillem; Sañudo Zotes, Eva Carolina; Universitat de Barcelona. Departament de Química Inorgànica i Orgànica
    [eng] This thesis explores the design and synthesis of molecular heterometallic lanthanide coordination compounds, highlighting their potential applications in quantum computing, as light-emitting devices, and for magnetic refrigeration. Two molecular systems are developed using β-diketonate ligands, incorporating selectively different lanthanides at distinct sites within the same molecular scaffold. A heterometallic trinuclear [LnLn'Ln] family is introduced, resulting in highly pure molecules. The stability and chemical selectivity of these compounds are validated through experimental techniques as well as theoretical calculations. The [ErPrEr] member of this family demonstrates the necessary requirements to act as a spin-based qubit within a potential molecular quantum gate. Additionally, the optical properties and energy transfer (ET) phenomena are investigated within [YbNdYb] and [ErNdEr] complexes. The [YbNdYb] complex shows efficient Nd-to-Yb ET, while the [ErNdEr] complex represents the first example of intramolecular double ET between Nd(III) and Er(III) metals. Furthermore, [GdLn'] systems are studied to incorporate both qubit and magnetic cooling characteristics within a single molecule. The [GdEr] complex displays the first case of a self- cooling qubit operating at low temperatures. On the other hand, [GdTm] complex shows an energy level structure that limits its efficiency as a self- cooling qubit. Overall, the results obtained in the thesis emphasize the innovative potential of heterometallic lanthanide coordination compounds in advanced or future technologies.
  • Miniatura
    logoOpenAccessTesi
    Optimització de processos en la industria farmacèutica
    (Universitat de Barcelona, 2024-11-21) Cuesta Turienzo, Víctor; Ariza Piquer, Xavier; Racamonde Villanueva, Marta; Universitat de Barcelona. Departament de Química Inorgànica i Orgànica
    [cat] La indústria farmacèutica ha exercit un impacte profund en la salut global durant les últimes dècades, contribuint de manera significativa a l'augment de l’esperança de vida. La seva missió principal és el desenvolupament i producció de medicaments que millorin la qualitat de vida dels pacients, seguint estrictes regulacions que garanteixin la seguretat i eficàcia dels principis actius farmacèutics (API). Un dels objectius fonamentals d’aquesta indústria és la millora contínua dels processos implicats en la producció d’APIs. Aquesta Tesi Doctoral es centra en la investigació d’eines innovadores per a optimitzar i millorar la producció d’APIs, amb l’objectiu d’avaluar i, si escau, incorporar tecnologies noves o ja utilitzades amb èxit en altres àmbits científics, però encara incipients en la indústria farmacèutica. Entre aquestes eines destaca la qualitat pel disseny (QbD), una metodologia que permet garantir la qualitat del producte des de les primeres etapes del procés de fabricació, mitjançant una millor comprensió de les reaccions i mecanismes implicats en la síntesi d’APIs. Una de les possibles accions de QbD és l’ús de models cinètics semiempírics, que ajusten els paràmetres cinètics de les reaccions basant-se en els resultats experimentals obtinguts al laboratori. Aquesta metodologia s’ha avaluat per a la síntesi de la Duloxetina i d’un intermedi clau en la ruta de síntesi d’un API, permetent optimitzar les condicions de reacció, controlar aspectes crítics com la conversió i la formació d’impureses, i millorar l’eficàcia i la robustesa del procés de síntesi. Finalment, ambdós processos han estat validats a escala industrial. Un altre aspecte de gran rellevància per a la indústria farmacèutica és el control de les impureses elementals (EI), com ara els metalls presents en els APIs a causa de l’ús de catalitzadors o de la contaminació ambiental. La presència d’aquests metalls en els productes finals ha de ser estrictament controlada, ja que poden ser tòxics i comprometre la salut dels pacients. Aquesta tesi avalua l’ús de la fluorescència de raigs X (XRF) com a tècnica d’anàlisi alternativa al plasma d’acoblament inductiu (ICP). L’XRF ofereix avantatges significatius, com ara la rapidesa, precisió, no destrucció de les mostres i una preparació de mostra més senzilla. S’han desenvolupat i validat amb èxit mètodes de quantificació de pal·ladi en mostres sòlides i líquides mitjançant XRF, a més d’explorar l’efecte matriu dels dissolvents en l’anàlisi de pal·ladi i fòsfor. L’ús d’aquesta tècnica ha permès monitorar la distribució del pal·ladi al llarg del procés de síntesi, garantint la seva eliminació i identificant els residus amb altes concentracions d’aquest metall. El pal·ladi és un dels metalls més utilitzats en la indústria farmacèutica, especialment en reaccions d’acoblament creuat C–C i C–N, gràcies a la seva alta activitat i capacitat de fer reaccionar substrats poc reactius. Tanmateix, el pal·ladi és un element escàs a la natura i de cost elevat, fet que converteix la seva recuperació en un àmbit d’investigació de gran interès. En aquesta Tesi s’han revisat els mètodes actuals de recuperació de pal·ladi i s’ha proposat un tractament senzill i econòmic amb bisulfit de sodi per concentrar els residus líquids amb alt contingut de Pd en residus sòlids amb altes concentracions percentuals. Això facilita la seva gestió i recuperació. En dos dels casos estudiats, el procés s’ha implementat a escala industrial, assolint recuperacions al voltant del 70%.
  • Miniatura
    logoOpenAccessTesi
    Synthesis, deposition and characterization of magnetic molecules on surfaces
    (Universitat de Barcelona, 2024-11-12) Gabarró Riera, Guillem; Sañudo Zotes, Eva Carolina; Aromí Bedmar, Guillem; Universitat de Barcelona. Departament de Química Inorgànica i Orgànica
    [eng] This doctoral thesis is dedicated to studying the synthesis and deposition of compounds with interesting magnetic properties on surfaces from an experimental perspective. The compounds studied are coordination compounds with properties ranging from single-molecule magnets (SMMs) to compounds with interesting properties for quantum computing (molecular qubits). These compounds can be simple molecules or more complex structures like metal-organic frameworks (MOFs). Through rigorous and numerous characterization techniques, the obtained systems have been studied in detail, with the aim of revealing how the compounds are affected during the deposition process and once they are in contact with the substrate. The thesis begins with a general introduction, reviewing the concept of using molecules as fundamental components for new devices, focusing on the phenomenon of SMMs and molecular qubits, as well as bidimensional MOFs. The introduction also covers the different experimental methods for depositing compounds on surfaces, as well as the most relevant techniques for characterizing the obtained systems. The first experimental chapter discusses the functionalization of substrates through the reaction known as silanization. This procedure allows obtaining different substrates with functional groups, such as carboxylate or terminal pyridine groups. This chapter presents a versatile method for different silanes and various substrates, such as silicon Si(100) or aluminum oxide in the form of single crystal (Al2O3(0001)) and microparticles. In Chapter 3, one of the substrates obtained in Chapter 2 is used to perform surface chemistry and deposit two compounds formed by lanthanides. The substrate is silicon with terminal carboxylate groups. These carboxylate groups aim to coordinate with the metals of the compounds, resulting in chemisorption. One of the compounds has dysprosium as the metal, while the other contains europium. The two compounds are analogous, as is their deposition. The dysprosium compound is an SMM, while the europium has very interesting luminescent characteristics that allow studying the deposition through these properties. The characterization performed allows us to conclude that the compounds remain intact on the surface and maintain their magnetic (in the case of dysprosium) and luminescent (in the case of europium) properties. Additionally, a percentage of the molecules form ordered structures on the surface, as observed through synchrotron radiation techniques. In Chapter 4, two molecular qubits containing copper and nickel, respectively, are deposited on silicon and aluminum oxide substrates with terminal pyridines. The compounds in their crystalline structure (in the bulk) have axial pyridines. Thus, through a ligand exchange reaction, these qubits could anchor to the surface. The compounds are deposited on the substrates and analyzed using numerous characterization techniques, which suggest that the compounds remain intact on the surface, forming very thin layers across the substrates. In Chapter 5, the deposition and growth of bidimensional MOFs with lanthanides on functionalized silicon and aluminum oxide substrates are investigated. The substrates obtained in previous chapters are used. The synthesis of different MOFs with dysprosium (SMM) and gadolinium (magnetocaloric effect and molecular qudit) as central metals is detailed. The characterization of the deposited MOFs is carried out using techniques such as atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS), which confirm that the MOFs have been correctly deposited and maintain their structural and magnetic properties. Additionally, X-ray magnetic circular dichroism (XMCD) techniques are used to demonstrate that a significant portion of the MOFs are oriented. Finally, the thesis concludes with a summary and general conclusions, along with comments on future steps to be taken.
  • Miniatura
    logoOpenAccessTesi
    Multiproperty materials: luminescent and/or magnetic coordination compounds containing f-block elements. Chirality
    (Universitat de Barcelona, 2024-09-20) Tubau Ribot, Ànnia; Vicente Castillo, Ramón; Universitat de Barcelona. Departament de Química Inorgànica i Orgànica
    [eng] The main goal of this Thesis work is the obtention of new lanthanide(III) coordination compounds presenting luminescence and magnetic properties, hence presenting multiproperty behavior. Moreover, by inducing chirality to the final compound, a third property is added to two families of the lanthanide complexes presented herein. In Chapter 2, ternary 4,4,4-trifluoro-1-phenyl-1,3-butanedionate (Btfa) mononuclear lanthanide compounds are obtained. Chapter 2.2 presents a Ce3+ family with general formula [Ln(Btfa3)(L)], where L is the 1,10-phenanthroline, 2,2’-bipyridil, 2,2';6',2"- terpyridine or 4,7-Diphenyl-1,10-phenanthroline. The magnetic properties of the Ce3+ family are studied to expand the limited knowledge on the slow relaxation of the magnetization of this cation. Moreover, the discussion of their magnetic properties is supported by Ab-initio calculations. For the second Btfa family, presented in Chapter 2.3 with the current [Ln(Btfa3)(4,4-dinonyl-2,2’-bipyridil)] general formula, luminescence in the solid state as well as in 1 mM chloroform solutions were studied. From the spectroscopic analyses, great stability of the compounds in DCM is observed. Due to the outstanding luminescence properties as well as great thermal stability presented for the Eu and Yb derivatives, these two compounds could be successfully used in the emissive layer of two different Organic Light Emitting Diode (OLED) devices. Moreover, the Dysprosium analogue of this family showed Single Ion Magnet (SIM) behavior and sensitized luminescence, hence multiproperty characteristics. In Chapter 3, four families of lanthanide fluorobenzoates derived from the 2- fluorobenzoic acid (2-HFBz) and 2,6-difluorobenzoic acid (2,6-HF2Bz) are obtained. For these compounds, the main goal is to increase the emission quantum yield of the Eu and Tb derivatives by designing new synthetic routes in order to completely remove the coordinating H2O molecules from the Ln3+ chemical environment. Four different families of dinuclear compounds were obtained. Water molecules could not be totally removed from the Ln3+ coordination sphere in structures containing the 2- FBz ligand with the general formula [Ln2(μ-2FBz)4(2FBz)2(H-2FBz)2(H2O)2] and (PPh4)2[Ln2(μ-2-FBz)2(2-FBz)6(H2O)2]. Whereas in compounds derived from 2,6- F2Bz ligand, two different dinuclear anhydrous structures with the general formula (HPy)2[Ln2(μ-2,6-2FBz)4(NO3)4] and (HPy)2[Ln2(μ-2,6-2FBz)4(2,6-2FBz)4] were obtained. The Eu and Tb compounds of these flurorobenzoate families presented good luminescence properties. Moreover, synthesis with Ce, Nd, Dy, Er and Yb where also synthetized to study both properties, luminescence and slow relaxation of the magnetization. The dinuclear Dysprosium compounds derived from 2,6-F2Bz ligand, showed Single Molecular Magnet (SMM) behavior. Finally, in Chapter 4, the chirality property is added to the luminescent and magnetic characteristics of the final compounds. This is accomplished by using the enantiomerically pure R- and S--methoxyphenylacetic acid (R- and S-HMPA) and R and S-2-phenylbutanoic acids (R and S-2-HPhBut). In compounds derived from the enantiomerically pure R/S-HMPA acids and 1,10- phenathroline chromophore ligand, 1D chiral polymeric chains were obtained with the general formula [Ln(-R/S-MPA)(R/S-MPA)2(phen)]n. Circular Polarized Luminescence (CPL) and Circular Dichroism (CD) spectra are measured for the Eu and Tb analogues in the solid state. Moreover, the Ce, Nd, Dy and Er, 1D chiral chains presented slow relaxation of the magnetization added to the sensitized luminescence of the Nd, Dy and Er compounds. With the enantiomerically pure R/S-HPhBut acid and the 4,7-Diphenyl-1,10- phenanthroline chromophore ligand, dinuclear lanthanide coordination compounds with the general formula [Ln2(-R-2-PhBut)4(R-2PhBut)2(Bphen)2] were obtained. The compounds undergo a structural change (from structure a to structure b) on increasing the atomic number along the lanthanide series (Nd to Yb). For the Eu and Tb enantiomeric pairs, CD and CPL spectra were measured in solid state as well as in 1mM DCM solutions with improved chiroptical properties for the solution samples. The significant difference seen in the CD and CPL spectra from solid to solution samples, account to a structural change when dissolving the compounds into the DCM solutions. Moreover, the Nd, Dy, Yb, Sm derivatives were synthetized and all present luminescence as well as slow relaxation of the magnetization (for Nd and Yb) and SMM behaviour, for the Dy compound.
  • Miniatura
    logoOpenAccessTesi
    Triplet harvesting of gold(I) supramolecular complexes and their applications
    (Universitat de Barcelona, 2024-10-25) Aquino Samper, Araceli de; Rodríguez Raurell, Laura; Lima, João Carlos dos Santos Silva e Pereira de; Universitat de Barcelona. Departament de Química Inorgànica i Orgànica
    [eng] This thesis has been done under the supervision of Prof. Laura Rodríguez (Inorganic Chemistry Section, Universitat de Barcelona) and Prof. João Carlos Lima (LAQV REQUIMTE, Universidade Nova de Lisboa). Over these four years, several gold(I) organometallic complexes with different structural characteristics have been synthesized. The compounds present different nuclearities (number of metal atoms) and different chromophores and ancillary ligands. The different parts of the molecules play a direct influence on their resulting luminescent properties. Since gold(I) displays a linear geometry, the chromophores have been coordinated in one of these positions, in the other one, different phosphanes, and diphosphanes as ancillary ligands. The main aim of this Doctoral Thesis is to study the luminescent properties and photophysics of these compounds in order to deeply understand how to efficiently promote the harvesting of triplet excited states, Tn, which are those responsible for the resulting phosphorescence emission, in order to obtain room temperature phosphorescence materials (RTP). Other applications have been explored, such as sensing water pollutants and singlet oxygen production. The interest in preparing compounds suitable for RTP materials relies on the fact that when producing excitons through electricity, 25% of them populate the Sn states, while 75% of them harvest the Tn instead. The forbidden character of the triplet excited state and its lower energy favours non-radiative decays. Hence, the use of an efficient way to obtain luminescent materials with high phosphorescence quantum yield is a challenge. On the other hand, the high sensitivity of luminescence is of great relevance to be used to prepare luminescent chemosensors. The use of phosphorescence sensors can help detect other types of contaminants that present intrinsic fluorescence emission that appears at shorter wavelengths. Finally, the production of singlet oxygen has been widely studied in the last years, with great potential in several research fields, such as photodynamic therapy (promoting the formation of ROS species that can attack carcinogenic cells) or catalytic reactions (using the singlet oxygen specie as a green catalyst). The advantage is that singlet oxygen is generated from oxygen, O2, which is very abundant in our atmosphere and can be produced through energy transfer from triplet excited states of molecular sensitizer, leading to the quenching of these states. This energy transfer can take place because the ground state of the O2 is a triplet, which permits the simultaneous transition of both triplets (molecular sensitizer and dioxygen) to the singlet state (excited singlet state of dioxygen and ground singlet state of the molecular sensitizer). Compounds with heavy atoms in their chemical structure, that can have populated the triplet excited state, are good molecular sensitizers, favouring the production of singlet oxygen instead of giving rise to phosphorescence emission. This PhD thesis is divided in different chapters that contain different families of gold(I) complexes displaying diverse structures. The presence of the gold(I) metal unit is crucial for promoting what is called “heavy atom effect”, which induces the promotion of the population of Tn states. The phosphanes and diphosphanes used have been crucial to modulate their solubilities and, also, the intra- and intermolecular supramolecular interactions present in the complexes. These interactions can modify the luminescent properties that the compounds present. Not only π···π and C-H···π interactions can be promoted, but also the so-called aurophilic contacts. Different characterization techniques have been used to evidence the pure formation of the organic and organometallic molecules (1H and 31P NMR, IR, ESI, MALDI-TOF, and DRX). Their luminescent properties have been analysed through Uv-Vis absorption and emission spectra under different conditions such as air-equilibrated, N2-saturated, solid, low temperature, and immobilized into organic polymeric matrices. Their luminescence lifetimes and quantum yields have been also measured. All these characterization techniques have been done in our groups’ facilities at the University of Barcelona. Several photophysical characterization require the use of the laser flash photolysis equipment, and these measurements have been done at the Universidade Nova de Lisboa facilities at the LAQV@REQUIMTE (CHARM group), during a short stage period. These measurements have been crucial for this work since it helped us to calculate the quantum yields of the formation of the triplet excited states (φT). All in all, we have tried to give a bit of light on the analysis of the photophysical parameters of gold(I) complexes, mainly regarding the effects that can affect the triplet harvesting and resulting derived properties (room temperature phosphorescence vs singlet oxygen production).
  • Miniatura
    logoOpenAccessTesi
    Síntesi d’un pèptid terapèutic: Un estudi metodològic vers la producció a escala de planta pilot
    (Universitat de Barcelona, 2023-12-12) Teruel Sánchez, Carolina; Nicolás Galindo, Ernesto; Racamonde Villanueva, Marta; Universitat de Barcelona. Departament de Química Inorgànica i Orgànica
    [cat] Tradicionalment, els fàrmacs de baix pes molecular (PM < 500 Da), coneguts com “molècules petites”, han predominat en el tractament de les malalties humanes, encara que en les últimes dècades els productes biològics de pes molecular elevat (PM > 5000 Da) han anat agafant força en el mercat gràcies als avanços en la biotecnologia, al permetre sintetitzar productes com proteïnes terapèutiques, anticossos o gens. No obstant, els pèptids terapèutics, definits com a compostos que es troben en la frontera entre les molècules petites tradicionals i les macromolècules d’origen biològic, són objectius molt rellevants en la recerca de nous fàrmacs pel que fa a la diversitat de funcions biològiques en les que intervenen, i representen un 10 % dels fàrmacs aprovats per l’Administració d’Aliments i Medicaments d’Estats Units (FDA) en els darrers 7 anys. Fins a la data, l’empresa Esteve Química ha centrat les seves investigacions i produccions en fàrmacs de molècules petites, i a partir de l’interès creixent de la comunitat farmacèutica en descobrir i desenvolupar nous pèptids terapèutics, l’empresa, junt amb la col·laboració de la Universitat de Barcelona, va decidir iniciar una línia d’investigació per a desenvolupar metodologies amb l’objectiu d’arribar a produir-los i comercialitzar-los. Amb aquest propòsit, un nou pèptid terapèutic de 17 aminoàcids anomenat Fexapotide Triflutat (FT), indicat pel tractament de la hiperplàsia benigna de pròstata (HBP) i que actualment es troba en espera per ser aprovat per la FDA per la seva comercialització, va ser el pèptid escollit per a dur a terme els estudis preliminars al laboratori i el posterior escalat del procés amb l’objectiu d’arribar a produir pèptids a escala de planta pilot a l’empresa. En l’inici d’aquesta col·laboració, es va dur a terme una Tesi Doctoral realitzada per Macarena Duran on es va proposar una estratègia sintètica per preparar FT a través d’una aproximació convergent, que consisteix en un enfoc híbrid de les dues opcions que es coneixen per sintetitzar químicament pèptids: la síntesi en fase sòlida (SPPS) i la síntesi en solució (SPS). El FT es va dividir en 3 fragments peptídics protegits: un dipèptid sintetitzat en solució i un hexapèptid i un nonapèptid sintetitzats en fase sòlida. Aquests fragments es van condensar en solució fins a obtenir el pèptid d’interès totalment protegit i en l’última etapa del procés es va desprotegir per obtenir FT. Com a resultat del treball preliminar, es van obtenir unes condicions experimentals adequades per a la obtenció de FT a escala de laboratori que, en la present Tesi Doctoral, s’han intentat millorar amb l’objectiu d’obtenir un procés eficient, ràpid, econòmic i segur, a més de complir amb els requeriments de les autoritats reguladores, per tal de poder portar la síntesi del pèptid d’interès a escala de producció. En aquesta investigació, s’ha posat especial atenció en el desenvolupament de mètodes analítics pel seguiment de les reaccions en fase sòlida per tal de superar un dels majors inconvenients de l’escalat de la fase sòlida. A més, s’han dissenyat nous reactors econòmics que permeten dur a terme l’escalat de la SPPS en reactors convencionals utilitzats en Esteve Química per a la síntesi en solució. A partir dels estudis de les reaccions d’acoblament d’aminoàcid i eliminació del grup Fmoc en SPPS es va poder dur a terme l’escalat de la síntesi dels fragments peptídics protegits, obtenint 28 g de l’hexapèptid i 37 g del nonapèptid amb pureses cromatogràfiques del 95,5 % i 96,5 % respectivament. L’estudi de les condicions experimentals en els acoblaments dels fragments peptídics en solució per donar el pèptid desitjat FT van permetre obtenir 26 g del precursor del FT amb una puresa cromatogràfica del 81,8 % i les millores condicions trobades per la desprotecció del precursor i obtenció de FT van portar a obtenir el pèptid terapèutic amb una riquesa per 1H-RMN de 92,2 %.
  • Miniatura
    logoOpenAccessTesi
    Self-assembled molecules as efficient selective contacts in translucent quantum-dot light emitting diodes
    (Universitat de Barcelona, 2023-12-20) Kumari, Sarika; Martínez-Ferrero, Eugenia; Palomares-Gil, Emilio; Universitat de Barcelona. Departament de Química Inorgànica i Orgànica
    [eng] Since the last two decades, nanotechnology has been revolutionary for representing small solutions to the big problems. Nanoscience and Nanotechnology spread from the area of Electronics, Energy and Environment to Biomedicine, Food or Textile where it has made possible to selectively target the cells to repair the damaged genes. It has also made possible to convert more sunlight into energy with efficient solar panels. Nanostructured materials make faster and more efficient microchips. It also contributes to make biosensors to detect pollutants in bodies. Today, nanomaterials have made possible to fabricate the LEDs of different colours. Colloidal quantum dots technology has drawn a huge attention in the academia and industry since last decade. Quantum dots are also called “Artificial Atoms” because they have discrete energy levels just like atoms. QDs are zero dimensional particles showing quantum confinement effect which means that their size comparable to Bohr radius and their colour can change with their size which is typically between 2-10 nm. On the other hand, these materials show excellent optical properties including high absorption, strong and narrow emission with high colour purity making them suitable for various applications. Perovskites are crystalline materials with the structure of calcium titanium oxide. They are extensively used for several applications because of their easy manufacturing process, abundance, low cost, and great flexibility. Metal halide perovskites are popular for their vast range of application in optoelectronic devices while metal oxide perovskites are widely used in chemical, electrochemical and photocatalysis. Self-assembled molecules (SAMs) are a class of materials which can attach to any substrate modifying the work function of the electrode for their diverse application. They consist of three components including terminal group, spacer group and anchoring group. SAMs are used to make organic and perovskite solar cells with better efficiency and stability. Nowadays, their application in perovskite LEDs have also emerged. Light emitting diodes (LEDs) works on the principle of electroluminescence. When a forward bias is applied to the device between the anode and cathode, the electrons flows towards the cathode and the holes towards anode. Majority charge carriers from the corresponding layers flows towards the emissive layer (if they can cross the barriers) by making the emissive layer negatively charged. Direct band gap semiconductors lead to the energy difference as the electron recombines to the holes by radiative recombination leading to the generation of photons. By the annihilation of an electron and hole, one photon generates. The band gap and chemical structure of the emissive material determines the color of the electroluminescence which is released from the device. The present thesis is focused on the synthesis of perovskite nanocrystals and their application in perovskite nanocrystal LEDs (PeLEDs) and the preparation of QDLEDs based on cadmium selenide QDs. We have used SAMs as hole transporting layer in PeLEDs which is a good alternative to the conventional hole transport materials (HTMs). SAM are good for the overall performance of devices including luminance and stability but also promotes thin sized LEDs. With this regard, we have also employed a thin layer of PDINO as electron transport material (ETM) for fabricating red QDLEDs in combination with commercial CdSe@ZnS quantum dots as emissive material. Finally, we have performed doping of a rare-earth element Dysprosium (Dy) in the methylammonium bromide (MAPbBr3) Perovskite lattice at different concentration to find the optimum for our LEDs.
  • Miniatura
    logoOpenAccessTesi
    Fighting bacteria. Synthesis and study of Polymyxin derivates to improve their therapeutic properties
    (Universitat de Barcelona, 2023-11-10) Pascual i Pérez, Marina; Rabanal Anglada, Francesc; Cajal Visa, Yolanda; Universitat de Barcelona. Departament de Química Inorgànica i Orgànica
    [eng] Multidrug resistant bacteria have grown to be a significant medical concern as a result of decades of excessive antibiotic usage and overuse in human medicine, agriculture, and the animal industry. In this context, there is a pressing need for the development of new, secure, and potent antimicrobials, especially against Gram-negative bacteria. A United Nations report estimates that infections caused by antimicrobial resistance already cause at least 700,000 deaths per year and that this number could rise to 10 million deaths per year by 2050 if no action is taken. Polymyxins are cationic lipopeptides naturally produced by Gram-positive bacteria Paenibacillus polymyxa which are very selective against Gram-negative bacteria. Polymyxins were discovered in the 1940s and used for around 20 years, until its administration was interrupted in the 1970s due to the nephrotoxicity and neurotoxicity that patients experienced after intravenous administration. Despite this, the increase of resistance to antibiotics forced the restoration of polymyxin use as a last line-therapy against multidrug resistant bacteria. This thesis presents the synthesis and characterization of 18 novel polymyxin-based peptides using solid phase synthesis, including a scope to determine the best conditions to perform a scale-up. These novel peptides have been designed with a redox active disulfide bond within the peptide backbone with the aim of reducing the toxicity of natural polymyxins. Besides this, several modifications were introduced in the sequence, especially in the N-terminal fatty acid, trying to balance activity with reduction of toxicity. Various microbiological and biophysical experiments were used to investigate the biological activity and mode of action of the synthetic peptides and two peptides were selected to perform in vivo tests in mice, providing robust evidence of their potential as therapeutic agents, forming a strong foundation for further research.
  • Miniatura
    logoOpenAccessTesi
    Advances in Asymmetric Catalytic Reactions: Novel Methodologies and Synthetic Applications
    (Universitat de Barcelona, 2023-11-03) Bellido Muñoz, Marina; Riera i Escalé, Antoni; Universitat de Barcelona. Departament de Química Inorgànica i Orgànica
    [eng] This doctoral thesis aims to explore various synthetic methodologies and their corresponding applications in the field of asymmetric catalysis. More specifically, we have focused on the preparation of prochiral compounds using metal catalysts. These compounds, such as terminal olefins, have undergone asymmetric hydrogenation in order to furnish enantiomerically enriched compounds. Indeed, the developed procedures can be divided in the following: The design and synthesis of a novel chiral N-bridged diphospane ligand, named MAdPHOS. This ligand features two distinct phosphanes: a P-stereogenic atom and a achiral, bulky one. The first P* is substituted with a tert-butyl/methyl moiety, enhancing enantiotopic differentiation. Whereas the diadamantylphosphane fragment, -PAd2, incorporates crystallinity, rigidity and bulkiness. This C1- symmetric ligand was synthesized via a two-steps process as a crystalline solid. Due to the N-bridge, it allows the NH/PH tautomerization, similar to its predecessor, the MaxPHOS ligand. The enantiopure ligand has been coordinated to Rh(I), and the resulting complex has been applied in the asymmetric hydrogenation of benchmark substrates. Additionally, we have assessed MAdPHOS’s sigma donor capacity, air stability and the isolation of the free ligand. The possibility of isolating the free MAdPHOS has allowed its coordination to other sensitive metals, like Ni(0). The synthesis of homoallylic sulfones by derivatization of homoallylic alcohols analogs. The regioselective preparation of these alcohols was achieved via the oxetane ring-opening catalyzed by a borane. The replacement of the alcohol group by the sulfonyl provided crystallinity and eased the separation of the possible regioisomers through flash chromatography. Successful purifications of homoallylic sulfones allowed for their enantioselective hydrogenation using a commercially available Ir-catalyst. The results obtained for the family of 12 homoallylic sulfones were up to 98% ee. Taking advantages of the chemical versatility of the SO2R group, the developed methodology was applied to the total synthesis of (−)-⍺- curcumene. The optimization of the previously mentioned 2,2-disubstituted oxetanes ring-opening reaction towards the corresponding homoallylic alcohols. We realized that a less commonly used Lewis acid, Al(C6F5)3, significantly improved the results by reducing the formation of a dimeric specie that appeared when the borane was used for electron-rich oxetanes. This Al-based super LA is bulkier and stronger than its B analog and allows the regioselective isomerization under mild conditions with a broad substrate scope. The synthetic applicability of this novel methodology was demonstrated in the enantioselective formal synthesis of (R)-(−)-curcuquinone and the total synthesis of the σ1 receptor agonist, (R)-RC-33. The development of an one-pot Pd-catalyzed three-component tandem reaction for the preparation of 2- aryl allyl sulfones. The tandem process involves a Suzuki-Miraura reaction and an allylic substitution. The reaction was found to be regioselective, robust and modulable. A variety of boronic acids and sulfones were screened, yielding good to excellent results towards terminal olefins. The reaction mechanism was studied by means of control experiments, DFT calculations and kinetic analysis. Allylic sulfones were subsequently hydrogenated employing the commercially available threonine-derived (UbaPHOX) iridium complex, affording chiral β-methyl sulfones with up to 98% ee. Furthermore, the expansion to other nucleophiles, such as secondary amines, has also been explored to afford 2-aryl allyl amines.
  • Miniatura
    logoOpenAccessTesi
    Design of Catalytic Systems based on Halogen Bonding Interactions: Synthesis and Application in Catalytic Reactions
    (Universitat de Barcelona, 2023-09-01) Martínez Bascuñana, Alba; Vidal i Ferran, Anton; Núñez Rico, José Luis; Universitat de Barcelona. Departament de Química Inorgànica i Orgànica
    [eng] The use of supramolecular interactions in catalysis has been widely studied and exploited for the straightforward preparation of the backbones of an array of structurally diverse stereoselective catalysts. In addition to the broad application of halogen bond donors as organocatalysts, the use of this non covalent interaction has been also employed for the preparation of catalytically active complexes. Our group pioneered the use of halogen bonding interactions for the construction of bidentate phosphorus ligands by assembly of suitably designed phosphorus(III)-based complementary ligands (XBphos Rh C1). The present doctoral thesis encompasses the synthesis and study of halogen bond-assembled complexes based on rhodium(I) and iridium(I) metal centers as well as their application in catalysis. We initially directed our research efforts to the effects that modifications on the halogen bond acceptor and donor ligands cause on the structure of the final rhodium(I) complexes. Structurally diverse halogen bond acceptor and donor ligands have been designed, synthesized, and subsequently tested in the preparation of halogen bond-assembled rhodium(I) complexes. The final complexes have been fully characterized by spectroscopic techniques in solution and in the solid state. It has been demonstrated that halogen bond acceptors containing a phosphaamidine moiety efficiently lead to halogen bond assembled complexes in combination with (2-iodo-3,4,5,6-tetrafluorobenzene)phosphane-based halogen bond donor ligand L2. On the other hand, substitution of the iodo group in L2 by a bromo or fluoro group led to changes in the Rh−P complexation behavior. Afterwards, a series of XBphos-Rh C1 analogues incorporating diverse counterions were successfully synthesized and fully characterized. These halogen bonded complexes have been successfully applied in the hydroboration reaction of terminal alkynes with the aim of maximizing the regioselectivity of the hydroboration of alkynes towards the branched alkenyl boronates by variation of the counterion. We demonstrated that the stronger the coordination ability of the counterion, the higher the activity and selectivity towards hydroboration products were. Our study concluded that linear and inactivated alkyl-substituted alkynes led to the highest levels of chemo- and regio-selectivity in the hydroboration reaction. Moreover, the practicality of our synthetic method was demonstrated by developing a one-pot hydroboration/Csp2−Csp2 coupling process. Then, we expanded the use of our halogen bond-assembled rhodium complexes as a suitable catalyst in other chemical transformations of interest. Efficient intramolecular [4+2] cycloadditions of dien-γ-ynes mediated by the halogen-bonded rhodium(I) complex XBphos-Rh-BArF in combination with a silver(I) salt have been developed. The cooperative action of the Rh/Ag derivatives efficiently leads to the corresponding [4+2] cycloadducts (yields ranging from 66% to 99%) with high selectivity. The synthetic protocol features simple operation and good functional group tolerance and represents a good example of bimetallic cooperation. Studies aimed at determining the role of rhodium(I) and Ag(I) derivatives were performed and revealed that both metallic derivatives are required for the reaction to take place. Finally, research efforts were directed to the expansion of the structural diversity of the XBphos-metal complexes to iridium(I) halogen-bonded complexes. Two closely related halogen bonded iridium complexes [Ir(CO)2(κ3I,P,P L1·L2)]BArF C9 and [Ir(CO)(κ3I,P,P L1·L2)]BArF C10 have been successfully prepared and characterized in solution and in the solid state. NMR spectroscopic analysis revealed an equilibrium between both iridium complexes, involving exchange of one CO molecule taking place in solution. Crystals suitable for X-Ray analysis allowed us to unequivocally elucidate the structure of both iridium(I) complexes: trigonal bipyramidal geometry in case of C9 and a square planar geometry in the monocarbonyl derivative C10. Our halogen bond assembled complex C9 has been efficiently applied in the consecutive double intra- and intermolecular hydroalkoxylation of alkynyl alcohols for the synthesis of O,O ketal products. The best results have been achieved when using linear alkynyl alcohols and more preorganized substrates that led to the formation of O-containing spiro-type compounds.
  • Miniatura
    logoOpenAccessTesi
    Exploring the heavy atom effect and supramolecular assemblies of Au(I) and Pt(II) complexes
    (Universitat de Barcelona, 2023-07-14) Romo Islas, Guillermo; Rodríguez Raurell, Laura; Universitat de Barcelona. Departament de Química Inorgànica i Orgànica
    [eng] This thesis is mainly focused on studying the photophysical properties of Au(I), Ag(I), Cu(I), and Pt(II) coordinated compounds. This work can be divided into two parts: on the one hand, the compounds of the group 11 metals and, on the other hand, the Pt(II) compounds. In the case of the group 11 metals, Au(I) compounds with different chromophore groups have been synthesized. These compounds contain the pyridyl diphenylphosphane ligand in their structure. These compounds were designed to be used as supports. They allow the introduction of a second metal, which promotes the formation of metallophilic interactions. For the Pt(II) compounds, the synthesis of [N^N^N] ligands with different structural modifications has been carried out in order to modulate the electronic properties in the resulting coordination compounds. Various neutral ligands, such as pyridines and diphosphines, were used to study the effect of coordination at the fourth available position in the Pt(II) atoms. These ligands have been rationally chosen in order to rationalize the effects of these structures on the photophysical properties of the compounds, with the aim of modifying and/or generating supramolecular structures supported by non-covalent interactions. The design of the different compounds was aimed at promoting the generation of singlet oxygen in solution by forming structures containing a large number of metal atoms. The research group worked on the development of a new methodology for the detection of this specie in solution. The method used was a direct measurement method. This method was applied to most of the compounds synthesized in this work. It helped to lay the foundation for the design of molecules with higher activities as chemical photosensitizers.
  • Miniatura
    logoOpenAccessTesi
    Synthesis and characterization of multinary group 10-11 metal-based nanocrystals
    (Universitat de Barcelona, 2023-07-17) Lin, Mengxi; Figuerola i Silvestre, Albert; Rodríguez Raurell, Laura; Universitat de Barcelona. Departament de Química Inorgànica i Orgànica
    [eng] Nanostructured semiconductors have gained significant importance due to their size- and morphology-tunable physical properties, and their ability to play a critical role in various fields such as energy conversion and theragnostic. Hybrid and multinary nanocrystals (NCs) have further enhanced the design complexity of nanostructures, offering new properties and synergies beyond those of individual materials. The thesis focuses on the synthesis and characterization of multinary group 10-11 metal-based chalcogenide nanocrystals, consisting of an introduction chapter and six chapters of results regarding different studied systems. Chapter 2 presents a new and easy colloidal synthetic method to form Au–Ag2X (X = S, Se) heterodimers. The method involves mixing pre-synthesized faceted Ag2S or hexagonally-shaped Ag2Se NPs with Au NPs by stirring at room temperature. The final product is observed and measured using transmission electron microscopy (TEM) and x- ray diffraction diffractometer (XRD) techniques for preliminary morphological and structural characterization. In-depth chemical and structural characterization is performed using high-resolution TEM and scanning transmission electron microscopy-energy dispersive x- ray spectroscopy (STEM-EDS). The size, shape, ligand and solvent dependence of the reported method are also studied. Chapter 3 describes the synthesis of the hybrid/multinary Au-Cu-S system using cation exchange (CE) reactions between pre-synthesized Cu2-xS NCs and HAuCl4. The Au/Cu molar ratio and surfactant nature are the key factors for controlling the crystallographic structures of the final products. The use of non-reducing surfactant (tetraoctylammonium bromide, TOAB) promotes mainly the CE between two precursors, resulting in the formation of void nanostructures. The use of reducing surfactant (dodecylamine, DDA) results in the growth of metallic Au domain on the surface of Cu2-xS NCs NCs. At the highest Au/Cu ratio, Au2S phase is presented, indicating the completion of the full CE reaction. In addition, at an Au/Cu ratio of 6, the ternary phase composed of Au-Cu-S is formed with either of the above-mentioned surfactants. Chapter 4 focuses on the synthesis of the Ag-Cu-Se ternary system by a reaction between premade Ag2Se NPs and CuIPPh3 under stirring at room temperature. Two ternary phases are observed in the final product at different Cu/Ag molar ratios, one of which is eucairite AgCuSe and the other one is a new, unreported ternary phase composed of Ag, Cu, and Se. A quaternary system is also synthesized based on the reaction of the obtained ternary Ag-Cu-Se phase with an Au(I)-complex. Chapter 5 includes the reproduction of ternary Pt-Cu-Se NPs with two different Pt/Cu molar ratios and assessments of their catalytic activities as photocatalysts for the production of hydrogen from aqueous ethanolic solutions. The synthesis of photocatalysts is carried out by a ligand-assisted CE reaction, and their activities are measured using UV-visible absorption spectroscopy, XRD, TEM, and photoelectrochemical measurements. In conclusion, the thesis provides valuable insights into the synthesis and characterization of multinary group 10-11 metal-based chalcogenide nanocrystals. The studies reveal the importance of controlling the crystallographic structures of the final products by tuning the Au/Cu molar ratio and surfactant nature in the hybrid/multinary Au-Cu-S system. The synthesis of new ternary phases and quaternary systems highlights the potential
  • Miniatura
    logoOpenAccessTesi
    Cyclometallated platinum compounds: optical and biological applications
    (Universitat de Barcelona, 2023-05-05) Lázaro Palacios, Ariadna; Rodríguez Raurell, Laura; Crespo Vicente, Margarita Ma.; Universitat de Barcelona. Departament de Química Inorgànica i Orgànica
    [eng] This Doctoral Thesis is focused on the synthesis of cyclometallated platinum compounds with different structural modifications rationally designed specifically for biological or optical applications. Specifically, tridentate [C,N,N’] and [N,C,N] cyclometallated compounds have been synthesised, differing in their oxidation state, the nature of the cyclometallated ligand, with variations in the rigidity and aromaticity, and with a variety of ancillary ligands. Several synthetic methodologies have been employed and the correct formation of the compounds has been checked by a great variety of techniques such as NMR and infrared spectroscopy, mass spectrometry elemental analysis and single crystal X-ray diffraction. Concerning biological applications, several compounds with anticancer properties have been successfully synthesised, obtaining some species with a high efficacy and minimal toxicity studied through cell viability assays. Additionally, several of the designed compounds presented a complete absence of cross-resistance and thanks to additional testing such as cyclic voltammetry, DNA interaction studies and cell-cycle phase distribution experiments, it has been observed that they present mechanisms of action not analogous to those of the clinically approved drugs. Concerning optical applications, the tuning of the structure of the compounds, especially in the cyclometallating ligands, has been key to achieve efficient phosphorescent platinum(II) compounds with various emissive states. Both emission quantum yields and lifetimes have been determined and DFT calculations have allowed a further understanding of the molecules excited states. Additionally, modification of the ancillary ligands, the solvent, the concentration or the presence of an additional metallic cation have been used as a strategy to promote a red-shift in the emission through the formation of aggregates or heterometallic compounds. Finally, one compound has been selected and tested for the preparation of a Light-Emitting Electrochemical Cell (LEEC) obtaining novel results for a platinum-doped device which are competitive with those reported in the literature for other metals and, to the best of our knowledge, the most efficient platinum system used for LEEC applications.