Hydrophobic ions for biomolecular intracellular delivery
Authorship
I.M.M.
Master in Chemistry at the Interface of Biology and Materials Science
I.M.M.
Master in Chemistry at the Interface of Biology and Materials Science
Defense date
02.12.2023 10:00
02.12.2023 10:00
Summary
The translocation of hydrophilic cargos across the cell membrane poses a significant challenge for their application as therapeutic compounds. Due to the amphiphilic nature of the phospholipid bilayer, peptides face barriers preventing their cellular entry. To address this, artificial membrane transporters have been developed. Carrier-mediated transport has garnered attention, with various methods and carriers including cell-penetrating peptides, ionophores, macrocycles, nanoparticles, lipids, liposomes, dendrimers, and boron clusters. While most strategies adopt an amphiphilic approach, they may lead to issues such as aggregation and non-specific membrane lysis. Notably, hydrophobic ions, situated near the superchaotropic ions in the extended Hofmeister series, present chemical properties that position them as promising candidates for facilitating the translocation of various cargos across the plasma membrane. To explore their potential, two hydrophobic ions are studied for their carrier activity in living cells. To achieve this goal, the first step involves measuring the cytotoxicity of these carriers in HeLa cells using a viability assay. Subsequently, the cell membrane transport of impermeable cargos is assessed. For this purpose, hydrophobic ions have been proved as carriers for both a cationic cytotoxic peptide (KLAK peptide) and a zwitterionic peptide (phalloidin toxin), which labels the cytoskeleton of cells. Utilising these cationic and zwitterionic peptides, the effective transport is analysed through cell viability assays and confocal fluorescence microscopy.
The translocation of hydrophilic cargos across the cell membrane poses a significant challenge for their application as therapeutic compounds. Due to the amphiphilic nature of the phospholipid bilayer, peptides face barriers preventing their cellular entry. To address this, artificial membrane transporters have been developed. Carrier-mediated transport has garnered attention, with various methods and carriers including cell-penetrating peptides, ionophores, macrocycles, nanoparticles, lipids, liposomes, dendrimers, and boron clusters. While most strategies adopt an amphiphilic approach, they may lead to issues such as aggregation and non-specific membrane lysis. Notably, hydrophobic ions, situated near the superchaotropic ions in the extended Hofmeister series, present chemical properties that position them as promising candidates for facilitating the translocation of various cargos across the plasma membrane. To explore their potential, two hydrophobic ions are studied for their carrier activity in living cells. To achieve this goal, the first step involves measuring the cytotoxicity of these carriers in HeLa cells using a viability assay. Subsequently, the cell membrane transport of impermeable cargos is assessed. For this purpose, hydrophobic ions have been proved as carriers for both a cationic cytotoxic peptide (KLAK peptide) and a zwitterionic peptide (phalloidin toxin), which labels the cytoskeleton of cells. Utilising these cationic and zwitterionic peptides, the effective transport is analysed through cell viability assays and confocal fluorescence microscopy.
Direction
MONTENEGRO GARCIA, JAVIER (Tutorships)
MONTENEGRO GARCIA, JAVIER (Tutorships)
Court
RIVADULLA FERNANDEZ, JOSE FRANCISCO (Chairman)
NAPPI , MANUEL (Secretary)
PELAZ GARCIA, BEATRIZ (Member)
RIVADULLA FERNANDEZ, JOSE FRANCISCO (Chairman)
NAPPI , MANUEL (Secretary)
PELAZ GARCIA, BEATRIZ (Member)
Zinc: The Master Regulator of Cell Signalling
Authorship
A.F.R.
Master in Chemistry at the Interface of Biology and Materials Science
A.F.R.
Master in Chemistry at the Interface of Biology and Materials Science
Defense date
02.16.2024 10:00
02.16.2024 10:00
Summary
Zinc is essential for the growth and development of microorganisms, plants, and animals. Serving as a cofactor in over 300 enzymes, zinc is crucial for stabilizing the structure of various proteins, including signaling enzymes, transcription factors, and zinc finger proteins. Many of these proteins are components of the ubiquitin pathway, such as E3 ligases and ubiquitin-binding domains (UBDs), which utilize zinc for both structural and functional purposes. Ubiquitination is vital for regulating cellular functions, and dysregulation of this process has been implicated in various diseases, including cancer. Understanding the mechanisms of ubiquitination is essential for elucidating the molecular basis of these pathologies as well as for design novel therapies. This study focuses on the RING domain, a conserved zinc-coordinated domain in E3 ligases, and the RanBP and A20 domains, ubiquitin-binding domains containing zinc-coordinated domains. Our project aims to develop synthetic RING and UBD variants by substituting zinc with less abundant metals to enable controlled activation. By structurally characterizing the RING domain of BRCA1, Npl4 NZF domain, and Rabex5 A20 domain, and investigating zinc affinity, we gain insights into metal and ubiquitin coordination. Understanding metalloproteins and synthetic UBDs development paves the way for targeted therapeutic interventions.
Zinc is essential for the growth and development of microorganisms, plants, and animals. Serving as a cofactor in over 300 enzymes, zinc is crucial for stabilizing the structure of various proteins, including signaling enzymes, transcription factors, and zinc finger proteins. Many of these proteins are components of the ubiquitin pathway, such as E3 ligases and ubiquitin-binding domains (UBDs), which utilize zinc for both structural and functional purposes. Ubiquitination is vital for regulating cellular functions, and dysregulation of this process has been implicated in various diseases, including cancer. Understanding the mechanisms of ubiquitination is essential for elucidating the molecular basis of these pathologies as well as for design novel therapies. This study focuses on the RING domain, a conserved zinc-coordinated domain in E3 ligases, and the RanBP and A20 domains, ubiquitin-binding domains containing zinc-coordinated domains. Our project aims to develop synthetic RING and UBD variants by substituting zinc with less abundant metals to enable controlled activation. By structurally characterizing the RING domain of BRCA1, Npl4 NZF domain, and Rabex5 A20 domain, and investigating zinc affinity, we gain insights into metal and ubiquitin coordination. Understanding metalloproteins and synthetic UBDs development paves the way for targeted therapeutic interventions.
Direction
Mascareñas Cid, Jose Luis (Tutorships)
Mascareñas Cid, Jose Luis (Tutorships)
Court
RIVADULLA FERNANDEZ, JOSE FRANCISCO (Chairman)
NAPPI , MANUEL (Secretary)
PELAZ GARCIA, BEATRIZ (Member)
RIVADULLA FERNANDEZ, JOSE FRANCISCO (Chairman)
NAPPI , MANUEL (Secretary)
PELAZ GARCIA, BEATRIZ (Member)
Photooxidation of aromatic pollulants catalyzed by Atomic Quantum Clusters
Authorship
C.S.D.
Master's Degree in Chemical Research and Industrial Chemistry
C.S.D.
Master's Degree in Chemical Research and Industrial Chemistry
Defense date
07.18.2024 09:00
07.18.2024 09:00
Summary
Currently there is a large amount of non-biodegradable contaminants caused by intense anthropogenic activity, which cause a negative impact on human health and the environment. In recent decades, global production of Bisphenol A (BPA) has increased dramatically, which is why it is speculated that it will become the largest water contaminant in the future. To date, conventional water treatment methods have not been sufficiently effective in removing BPA. For this reason, in the present project the photooxidation of BPA catalyzed by atomic quantum clusters (AQCs) deposited in titanium oxide was studied. The results obtained in the degradation of BPA by varying the time, radiation source, type, charge and concentration of the different catalysts functionalized with silver atomic quantum clusters demonstrated to be a promising method to efficiently, economically and sustainably eliminate the levels of BPA in water.
Currently there is a large amount of non-biodegradable contaminants caused by intense anthropogenic activity, which cause a negative impact on human health and the environment. In recent decades, global production of Bisphenol A (BPA) has increased dramatically, which is why it is speculated that it will become the largest water contaminant in the future. To date, conventional water treatment methods have not been sufficiently effective in removing BPA. For this reason, in the present project the photooxidation of BPA catalyzed by atomic quantum clusters (AQCs) deposited in titanium oxide was studied. The results obtained in the degradation of BPA by varying the time, radiation source, type, charge and concentration of the different catalysts functionalized with silver atomic quantum clusters demonstrated to be a promising method to efficiently, economically and sustainably eliminate the levels of BPA in water.
Direction
VAZQUEZ VAZQUEZ, CARLOS (Tutorships)
BUCETA FERNANDEZ, DAVID (Co-tutorships)
VAZQUEZ VAZQUEZ, CARLOS (Tutorships)
BUCETA FERNANDEZ, DAVID (Co-tutorships)
Court
Sanmartin Matalobos, Jesus (Coordinator)
SOTO CASTINHEIRA, MANUEL (Chairman)
BELLO BUGALLO, PASTORA MARIA (Secretary)
Leao Martins, José Manuel (Member)
Sanmartin Matalobos, Jesus (Coordinator)
SOTO CASTINHEIRA, MANUEL (Chairman)
BELLO BUGALLO, PASTORA MARIA (Secretary)
Leao Martins, José Manuel (Member)
Visible-light photocatalysis in biological media
Authorship
A.R.S.
Master in Chemistry at the Interface of Biology and Materials Science
A.R.S.
Master in Chemistry at the Interface of Biology and Materials Science
Defense date
02.12.2023 10:00
02.12.2023 10:00
Summary
From a molecular perspective, biological chemistry delves into the chemical processes unfolding within living organisms. A comprehensive grasp of the cellular and molecular mechanisms that underlie biological functions is imperative for the diagnosis and treatment of various diseases. The capability to manipulate, observe, and modify cellular behavior stands as a vital component in advancing modern medicine. Nevertheless, the intervention in cellular machinery poses a significant challenge, necessitating tools capable of transforming substances within the cell interior, whether they are exogenous or endogenous. In pursuit of this, chemically pre-designed intracellular reactions, facilitating the introduction of unconventional functions into living cells, referred to as bioorthogonal reactions, have been devised. These reactions present a formidable task for the field of chemical biology. Despite the inherent challenges, the realm of bioorthogonal chemistry has witnessed substantial growth in recent decades, incorporating indispensable tools for manipulating biological settings. Emerging methods for executing biocompatible reactions through photocatalysis, propelled by visible light, have come to the forefront. These photochemical transformations align with the principles of bioorthogonal chemistry, giving rise to a new and exhilarating area of research known as bioorthogonal photochemistry. This work optimises and translates visible light photocatalytic reactions into aqueous and biological environments, advancing in the field of bioorthogonal chemistry and laying the foundations for synthetic bioorthogonal photocatalysis. The power of this development is exemplified by the application of the optimized system in the synthesis of an anticancer drug.
From a molecular perspective, biological chemistry delves into the chemical processes unfolding within living organisms. A comprehensive grasp of the cellular and molecular mechanisms that underlie biological functions is imperative for the diagnosis and treatment of various diseases. The capability to manipulate, observe, and modify cellular behavior stands as a vital component in advancing modern medicine. Nevertheless, the intervention in cellular machinery poses a significant challenge, necessitating tools capable of transforming substances within the cell interior, whether they are exogenous or endogenous. In pursuit of this, chemically pre-designed intracellular reactions, facilitating the introduction of unconventional functions into living cells, referred to as bioorthogonal reactions, have been devised. These reactions present a formidable task for the field of chemical biology. Despite the inherent challenges, the realm of bioorthogonal chemistry has witnessed substantial growth in recent decades, incorporating indispensable tools for manipulating biological settings. Emerging methods for executing biocompatible reactions through photocatalysis, propelled by visible light, have come to the forefront. These photochemical transformations align with the principles of bioorthogonal chemistry, giving rise to a new and exhilarating area of research known as bioorthogonal photochemistry. This work optimises and translates visible light photocatalytic reactions into aqueous and biological environments, advancing in the field of bioorthogonal chemistry and laying the foundations for synthetic bioorthogonal photocatalysis. The power of this development is exemplified by the application of the optimized system in the synthesis of an anticancer drug.
Direction
Mascareñas Cid, Jose Luis (Tutorships)
Mascareñas Cid, Jose Luis (Tutorships)
Court
RIVADULLA FERNANDEZ, JOSE FRANCISCO (Chairman)
NAPPI , MANUEL (Secretary)
PELAZ GARCIA, BEATRIZ (Member)
RIVADULLA FERNANDEZ, JOSE FRANCISCO (Chairman)
NAPPI , MANUEL (Secretary)
PELAZ GARCIA, BEATRIZ (Member)
dendritic complex coacervates as multiphase systems.
Authorship
J.M.R.H.
Master in Organic Chemistry (3ª ed)
J.M.R.H.
Master in Organic Chemistry (3ª ed)
Defense date
07.18.2024 09:00
07.18.2024 09:00
Summary
Cells are involved in numerous biomolecular reactions and processes that need precise regulation and organization to function effectively. Recently, coacervates have been used as a promising platform to create cell-like compartments called membraneless organelles (MLOs). Complex coacervates, formed by liquid-liquid phase separation (LLPS) of oppositely charged polyelectrolytes, are used as synthetic cellular compartments. Inspired by complex structures, researchers are now focusing on developing multiphase coacervates with similar hierarchical arrangements. In this study, we describe the formation of complex coacervates using two or three polycations in varying ratios, combined with an anionic dendrimer. By adjusting the charge ratio of one polycation we analyzed the formation of three-phase systems, allowing us to control multicompartmentation in these cell-like structures.
Cells are involved in numerous biomolecular reactions and processes that need precise regulation and organization to function effectively. Recently, coacervates have been used as a promising platform to create cell-like compartments called membraneless organelles (MLOs). Complex coacervates, formed by liquid-liquid phase separation (LLPS) of oppositely charged polyelectrolytes, are used as synthetic cellular compartments. Inspired by complex structures, researchers are now focusing on developing multiphase coacervates with similar hierarchical arrangements. In this study, we describe the formation of complex coacervates using two or three polycations in varying ratios, combined with an anionic dendrimer. By adjusting the charge ratio of one polycation we analyzed the formation of three-phase systems, allowing us to control multicompartmentation in these cell-like structures.
Direction
FERNANDEZ MEGIA, EDUARDO (Tutorships)
ESTEVEZ CABANAS, JUAN CARLOS (Co-tutorships)
FERNANDEZ MEGIA, EDUARDO (Tutorships)
ESTEVEZ CABANAS, JUAN CARLOS (Co-tutorships)
Court
VARELA CARRETE, JESUS ANGEL (Chairman)
Vela Gallego, Sonia (Secretary)
Martínez del Campo, Teresa (Member)
VARELA CARRETE, JESUS ANGEL (Chairman)
Vela Gallego, Sonia (Secretary)
Martínez del Campo, Teresa (Member)
Obtaining triaxial ceramic catalyst supports by 3D printing
Authorship
C.A.C.S.
Master's Degree in Chemical Research and Industrial Chemistry
C.A.C.S.
Master's Degree in Chemical Research and Industrial Chemistry
Defense date
09.16.2024 09:00
09.16.2024 09:00
Summary
The production/manufacturing of catalyst supports from triaxial ceramics using 3D printing technology is a cutting-edge technique in the porcelain industry. The study and preparation of samples for this work were conducted at the AFICEGA laboratory, where ceramic pastes undergo quality control (using various analysis methods) to determine their suitability for the production of ceramic materials. The results of these analyses verify that the raw materials meet the necessary conditions for porcelain manufacturing. Once the analysis phases are approved, rectangular test specimens are prepared to assess the mechanical behavior of the material, as well as its porosity at different firing temperatures. By determining the optimal firing temperature, the catalyst supports are then fabricated using a 3D printer, which provides the desired structure, enhancing the hardness of the material and its suitability for use as a catalyst. This study provides a detailed insight into the methodology employed for the production of porcelain materials and the significant advancements in this field through the use of new technological tools such as 3D printing, as an alternative for materials to support metal catalysts. The fabricated porcelain material offers significant benefits for use in the chemical industry, as it allows for the variation of porosity in its structure based on the firing temperature, facilitates the easy positioning of catalysts within its structure, and is easy to manufacture as it does not require complex preparations to be used as ink in 3D printers. Moreover, it offers the mechanical and thermal properties characteristic of porcelain ceramics, adding significant benefits for the chemical industry and the porcelain ceramics sector.
The production/manufacturing of catalyst supports from triaxial ceramics using 3D printing technology is a cutting-edge technique in the porcelain industry. The study and preparation of samples for this work were conducted at the AFICEGA laboratory, where ceramic pastes undergo quality control (using various analysis methods) to determine their suitability for the production of ceramic materials. The results of these analyses verify that the raw materials meet the necessary conditions for porcelain manufacturing. Once the analysis phases are approved, rectangular test specimens are prepared to assess the mechanical behavior of the material, as well as its porosity at different firing temperatures. By determining the optimal firing temperature, the catalyst supports are then fabricated using a 3D printer, which provides the desired structure, enhancing the hardness of the material and its suitability for use as a catalyst. This study provides a detailed insight into the methodology employed for the production of porcelain materials and the significant advancements in this field through the use of new technological tools such as 3D printing, as an alternative for materials to support metal catalysts. The fabricated porcelain material offers significant benefits for use in the chemical industry, as it allows for the variation of porosity in its structure based on the firing temperature, facilitates the easy positioning of catalysts within its structure, and is easy to manufacture as it does not require complex preparations to be used as ink in 3D printers. Moreover, it offers the mechanical and thermal properties characteristic of porcelain ceramics, adding significant benefits for the chemical industry and the porcelain ceramics sector.
Direction
FONDO BUSTO, MARIA MATILDE (Tutorships)
GUITIAN RIVERA, FRANCISCO (Co-tutorships)
FONDO BUSTO, MARIA MATILDE (Tutorships)
GUITIAN RIVERA, FRANCISCO (Co-tutorships)
Court
Sanmartin Matalobos, Jesus (Coordinator)
FIOL LOPEZ, SARAH (Chairman)
MOSQUERA MOSQUERA, JESUS (Secretary)
Rosales Villanueva, Emilio (Member)
Sanmartin Matalobos, Jesus (Coordinator)
FIOL LOPEZ, SARAH (Chairman)
MOSQUERA MOSQUERA, JESUS (Secretary)
Rosales Villanueva, Emilio (Member)
Diastereoselective Synthesis of Highly-Substituted Methylene Cyclobutanes via Pd-catalysis: Scope of the Reaction
Authorship
J.M.M.D.
Master in Chemistry at the Interface of Biology and Materials Science
J.M.M.D.
Master in Chemistry at the Interface of Biology and Materials Science
Defense date
02.12.2023 10:00
02.12.2023 10:00
Summary
Methylene cyclobutanes are insteresting structures that can be used in different targeted molecules in medicinal chemistry. Their inclusion in the core of pharmaceutical precursors supposes advantages such as conformational restriction of the molecule, capability of blocking metabolically labile sites or increase the binding affinities due to spatial arrangements of target proteins. Moreover, their use as bioisosteres of phenyl rings could reduce the melting point and increase the solubility of the precursors, one of the main issues in modern medicinal chemistry. Despite their interest, these structures have not been deeply studied due to the scarcity of efficient synthetic methods to access such strained cores. From literature precedents, most of the attempts to synthesize them is through Pd-catalyzed intramolecular cyclization of 1,5-dienes. During the Initiation Research Project, a stereoselective method that addresses these structures via Pd-catalyzed coupling between borylated 1,5-diene and 1-iodo-4-methoxybenzene was optimized, obtaining a set of preliminary conditions. Through this Master Dissertation Project, the final optimal conditions were set, and the scope of the reaction was studied. The results achieved in this research probe the applicability of the transformation, its functional group tolerance and the parameters that govern the mechanism of this reaction.
Methylene cyclobutanes are insteresting structures that can be used in different targeted molecules in medicinal chemistry. Their inclusion in the core of pharmaceutical precursors supposes advantages such as conformational restriction of the molecule, capability of blocking metabolically labile sites or increase the binding affinities due to spatial arrangements of target proteins. Moreover, their use as bioisosteres of phenyl rings could reduce the melting point and increase the solubility of the precursors, one of the main issues in modern medicinal chemistry. Despite their interest, these structures have not been deeply studied due to the scarcity of efficient synthetic methods to access such strained cores. From literature precedents, most of the attempts to synthesize them is through Pd-catalyzed intramolecular cyclization of 1,5-dienes. During the Initiation Research Project, a stereoselective method that addresses these structures via Pd-catalyzed coupling between borylated 1,5-diene and 1-iodo-4-methoxybenzene was optimized, obtaining a set of preliminary conditions. Through this Master Dissertation Project, the final optimal conditions were set, and the scope of the reaction was studied. The results achieved in this research probe the applicability of the transformation, its functional group tolerance and the parameters that govern the mechanism of this reaction.
Direction
FAÑANAS MASTRAL, MARTIN (Tutorships)
FAÑANAS MASTRAL, MARTIN (Tutorships)
Court
RIVADULLA FERNANDEZ, JOSE FRANCISCO (Chairman)
NAPPI , MANUEL (Secretary)
PELAZ GARCIA, BEATRIZ (Member)
RIVADULLA FERNANDEZ, JOSE FRANCISCO (Chairman)
NAPPI , MANUEL (Secretary)
PELAZ GARCIA, BEATRIZ (Member)
Synthesis and Self-assembly studies of Cyclic peptides: towards their Biorthogonal Formation Inside Living Cells.
Authorship
K.S.
Master in Chemistry at the Interface of Biology and Materials Science
K.S.
Master in Chemistry at the Interface of Biology and Materials Science
Defense date
02.12.2023 10:00
02.12.2023 10:00
Summary
As the need arises for more effective drug delivery to increase the effectiveness of conventional drugs for various diseases such as cancer, the controlled generation of bioactive molecules and drugs within living cells emerge as an alternative of great interest. In this regard, the in-situ formation of self-assembly cyclic peptide nanotubes appears as a powerful strategy due to their remarkable therapeutic capabilities. In addition, they could also be used as simple model of fibrillar structures present in cells. The long-term objective of this work is the development of a simple chemical protocol that allow the in cell catalyzed formation of peptide nanotubes using abiotic machinery. In this project, we begin by studying all elementary steps that can trigger the selective cyclization of linear peptides and the subsequent nanotube formation. To carry out this study, peptides with different structural characteristics were designed and synthesized that allowed addressing the most important stages of the process. Therefore, derivatives protected at their N-terminal ends with Alloc or Fmoc groups were prepared. These peptides should contain a carbonyl aldehyde at the C-terminus for which a solid phase methodology was developed that would allow their synthesis to be carried out efficiently. The synthesized peptides were cleaved from the resin, but we decided to leave the amino terminus group protected to be able to generate the cyclic derivatives in a controlled manner. In other to carry out the cyclization of the linear peptide under metal-catalyzed conditions, the Alloc protecting group was selected. Special conditions for its removal were developed using a Ruthenium (III) complex {[Cp(allyl)(HQ)Ru]+PF6-}. Once this group is removed the fast thiazolidine formation by reaction of the amino and thiol group of terminal Cysteine and the carbonyl moiety provided the cyclization of the peptides. Additionally, the subsequence self-assembly of the cyclic peptides into nanotubes in solution was also studied. The thioflavin T fluorescence assay provides clear evidence of the formation of b-sheet-type structures in aqueous solution, a key feature of cyclic peptide nanotubes. The influence of pH on the formation of tubular structures was evaluated to clarify the importance of balancing the cyclic peptide charges and the thiazolidine stability. The STEM images fail to show nanotubes structures, and the self-assembly of the cyclic peptides into nanotube is yet to be fully established in the content of this work. However, more investigation is need in this regard.
As the need arises for more effective drug delivery to increase the effectiveness of conventional drugs for various diseases such as cancer, the controlled generation of bioactive molecules and drugs within living cells emerge as an alternative of great interest. In this regard, the in-situ formation of self-assembly cyclic peptide nanotubes appears as a powerful strategy due to their remarkable therapeutic capabilities. In addition, they could also be used as simple model of fibrillar structures present in cells. The long-term objective of this work is the development of a simple chemical protocol that allow the in cell catalyzed formation of peptide nanotubes using abiotic machinery. In this project, we begin by studying all elementary steps that can trigger the selective cyclization of linear peptides and the subsequent nanotube formation. To carry out this study, peptides with different structural characteristics were designed and synthesized that allowed addressing the most important stages of the process. Therefore, derivatives protected at their N-terminal ends with Alloc or Fmoc groups were prepared. These peptides should contain a carbonyl aldehyde at the C-terminus for which a solid phase methodology was developed that would allow their synthesis to be carried out efficiently. The synthesized peptides were cleaved from the resin, but we decided to leave the amino terminus group protected to be able to generate the cyclic derivatives in a controlled manner. In other to carry out the cyclization of the linear peptide under metal-catalyzed conditions, the Alloc protecting group was selected. Special conditions for its removal were developed using a Ruthenium (III) complex {[Cp(allyl)(HQ)Ru]+PF6-}. Once this group is removed the fast thiazolidine formation by reaction of the amino and thiol group of terminal Cysteine and the carbonyl moiety provided the cyclization of the peptides. Additionally, the subsequence self-assembly of the cyclic peptides into nanotubes in solution was also studied. The thioflavin T fluorescence assay provides clear evidence of the formation of b-sheet-type structures in aqueous solution, a key feature of cyclic peptide nanotubes. The influence of pH on the formation of tubular structures was evaluated to clarify the importance of balancing the cyclic peptide charges and the thiazolidine stability. The STEM images fail to show nanotubes structures, and the self-assembly of the cyclic peptides into nanotube is yet to be fully established in the content of this work. However, more investigation is need in this regard.
Direction
Granja Guillán, Juan Ramón (Tutorships)
Granja Guillán, Juan Ramón (Tutorships)
Court
RIVADULLA FERNANDEZ, JOSE FRANCISCO (Chairman)
NAPPI , MANUEL (Secretary)
PELAZ GARCIA, BEATRIZ (Member)
RIVADULLA FERNANDEZ, JOSE FRANCISCO (Chairman)
NAPPI , MANUEL (Secretary)
PELAZ GARCIA, BEATRIZ (Member)
Towards an external dual chiral topology through orthogonal functionalization of alpha helical peptides
Authorship
A.F.B.
Master in Chemistry at the Interface of Biology and Materials Science
A.F.B.
Master in Chemistry at the Interface of Biology and Materials Science
Defense date
02.12.2023 10:00
02.12.2023 10:00
Summary
Alpha Helix is the most abundant secondary structure motif in nature, playing a crucial role in various biological processes. It often presents specific patterns of side chains within the alpha helix that gives distinct structural topologies, which determine its interactions with other molecules. However, visualizing these topologies in solution remains challenging, often requiring crystallization for X-ray diffraction analysis. Circular dichroism (CD) spectroscopy provides an easy and non-destructive way to observe chiral structures in solution. To investigate the external structural patterns of the alpha helix using CD spectroscopy, it is necessary to introduce chromophores that do not interfere with the characteristic amide signal of the alpha helix. One such class of chromophores is the SCOTfluors, which are based on the NBD. The final objective of this master project is the spectroscopic characterization of two topologies of inverse chirality within a single alpha helical backbone using circular dichroism. This involves the functionalization of the backbone with distinct chromophores thus allowing the observation of two exo-helices with opposite chirality. The synthesis of non-commercial SCOTFluors chromophores was performed to study the possible spectroscopic coupling and further explore hetero-chromophore interactions Control peptides were functionalized for the selection of the best chromophore pair for both exo-helixes. Once the chromophore pair was chosen, a double helix containing the two exo-helixes was synthesized. Despite the inherent complexity in the synthesis and purification processes, initial confirmation of a peptide containing the two exo-helices was obtained through a preliminary CD spectrum.
Alpha Helix is the most abundant secondary structure motif in nature, playing a crucial role in various biological processes. It often presents specific patterns of side chains within the alpha helix that gives distinct structural topologies, which determine its interactions with other molecules. However, visualizing these topologies in solution remains challenging, often requiring crystallization for X-ray diffraction analysis. Circular dichroism (CD) spectroscopy provides an easy and non-destructive way to observe chiral structures in solution. To investigate the external structural patterns of the alpha helix using CD spectroscopy, it is necessary to introduce chromophores that do not interfere with the characteristic amide signal of the alpha helix. One such class of chromophores is the SCOTfluors, which are based on the NBD. The final objective of this master project is the spectroscopic characterization of two topologies of inverse chirality within a single alpha helical backbone using circular dichroism. This involves the functionalization of the backbone with distinct chromophores thus allowing the observation of two exo-helices with opposite chirality. The synthesis of non-commercial SCOTFluors chromophores was performed to study the possible spectroscopic coupling and further explore hetero-chromophore interactions Control peptides were functionalized for the selection of the best chromophore pair for both exo-helixes. Once the chromophore pair was chosen, a double helix containing the two exo-helixes was synthesized. Despite the inherent complexity in the synthesis and purification processes, initial confirmation of a peptide containing the two exo-helices was obtained through a preliminary CD spectrum.
Direction
BERGUEIRO ALVAREZ, JULIAN (Tutorships)
BERGUEIRO ALVAREZ, JULIAN (Tutorships)
Court
RIVADULLA FERNANDEZ, JOSE FRANCISCO (Chairman)
NAPPI , MANUEL (Secretary)
PELAZ GARCIA, BEATRIZ (Member)
RIVADULLA FERNANDEZ, JOSE FRANCISCO (Chairman)
NAPPI , MANUEL (Secretary)
PELAZ GARCIA, BEATRIZ (Member)
Supramolecular redesign of amyloid peptides as antimicrobials
Authorship
A.H.G.
Master in Chemistry at the Interface of Biology and Materials Science
A.H.G.
Master in Chemistry at the Interface of Biology and Materials Science
Defense date
02.12.2023 10:00
02.12.2023 10:00
Summary
Amyloid fibers constitute one of the most abundant and important natural self-assembled structures. These supramolecular arrangements enable versatile assembly of diverse protein and peptide molecules under different conditions, which gives them promising potential as building blocks for the design of novel nanomaterials, for example as antibacterial agents or hydrogels. Our investigation occured at CiQUS from January to December 2023, focusing on the synthesis and characterization of two distinct amyloid peptides derived from the natural Amyloid Beta-42 peptide: Ac-GGVVIAK-NH2 and Ac-FFK-NH2 and the study of its ability to control supramolecular fibrillation by reversible decoration with glycan units. We have found that peptide Ac-GGVVIAJ-NH2 aggregates amorphously while Ac-FFK-NH2 aggregates in a star-like shape with higher fiber prevalence in slightly acidic pH (5.5). Several synthetic approaches to conjugate glycans of interest (i.e. reversible fibrillation inhibitors) to these peptides have been explored. We have demonstrated that the aggregation of AB fragments can be influenced by both amino acid sequence and pH values. By carefully controlling these two parameters, we aim to assemble innovative amyloid-based anomaterials for antimicrobial application and stimuli-responsive self-assembly in the future.
Amyloid fibers constitute one of the most abundant and important natural self-assembled structures. These supramolecular arrangements enable versatile assembly of diverse protein and peptide molecules under different conditions, which gives them promising potential as building blocks for the design of novel nanomaterials, for example as antibacterial agents or hydrogels. Our investigation occured at CiQUS from January to December 2023, focusing on the synthesis and characterization of two distinct amyloid peptides derived from the natural Amyloid Beta-42 peptide: Ac-GGVVIAK-NH2 and Ac-FFK-NH2 and the study of its ability to control supramolecular fibrillation by reversible decoration with glycan units. We have found that peptide Ac-GGVVIAJ-NH2 aggregates amorphously while Ac-FFK-NH2 aggregates in a star-like shape with higher fiber prevalence in slightly acidic pH (5.5). Several synthetic approaches to conjugate glycans of interest (i.e. reversible fibrillation inhibitors) to these peptides have been explored. We have demonstrated that the aggregation of AB fragments can be influenced by both amino acid sequence and pH values. By carefully controlling these two parameters, we aim to assemble innovative amyloid-based anomaterials for antimicrobial application and stimuli-responsive self-assembly in the future.
Direction
MONTENEGRO GARCIA, JAVIER (Tutorships)
MONTENEGRO GARCIA, JAVIER (Tutorships)
Court
RIVADULLA FERNANDEZ, JOSE FRANCISCO (Chairman)
NAPPI , MANUEL (Secretary)
PELAZ GARCIA, BEATRIZ (Member)
RIVADULLA FERNANDEZ, JOSE FRANCISCO (Chairman)
NAPPI , MANUEL (Secretary)
PELAZ GARCIA, BEATRIZ (Member)
Initiation of Vitamin D precursor synthesis with restricted side-chain mobility
Authorship
X.F.D.
Master in Organic Chemistry (3ª ed)
X.F.D.
Master in Organic Chemistry (3ª ed)
Defense date
09.13.2024 09:00
09.13.2024 09:00
Summary
As part of a programme aimed at initiating the synthesis of 1,25D3 hormone analogues with restricted mobility in the side chain at positions C20 and C22, and with possible selective properties in particular low calcemic action, molecular docking calculations and the synthesis of an intermediate compound of the synthetic plan were performed to arrive at a hormone analogue possessing a tricyclic CDE system which restricts mobility, all this starting from commercial Vitamin D2. Docking calculations were performed on different analogues, with the tricyclic system as a common structure, and differing in the side chain at position C22. They were carried out using the GOLD program and analysing the interactions between the ligand and the most important amino acids of the hVDR receptor binding domain.
As part of a programme aimed at initiating the synthesis of 1,25D3 hormone analogues with restricted mobility in the side chain at positions C20 and C22, and with possible selective properties in particular low calcemic action, molecular docking calculations and the synthesis of an intermediate compound of the synthetic plan were performed to arrive at a hormone analogue possessing a tricyclic CDE system which restricts mobility, all this starting from commercial Vitamin D2. Docking calculations were performed on different analogues, with the tricyclic system as a common structure, and differing in the side chain at position C22. They were carried out using the GOLD program and analysing the interactions between the ligand and the most important amino acids of the hVDR receptor binding domain.
Direction
PAZ CASTAÑAL, MANUEL MARIA (Tutorships)
MOURIÑO MOSQUERA, ANTONIO (Co-tutorships)
PAZ CASTAÑAL, MANUEL MARIA (Tutorships)
MOURIÑO MOSQUERA, ANTONIO (Co-tutorships)
Court
VARELA CARRETE, JESUS ANGEL (Chairman)
Vela Gallego, Sonia (Secretary)
Filippone , Salvatore (Member)
VARELA CARRETE, JESUS ANGEL (Chairman)
Vela Gallego, Sonia (Secretary)
Filippone , Salvatore (Member)
Analysis of feed and raw material
Authorship
M.D.C.V.P.
Master's Degree in Chemical Research and Industrial Chemistry
M.D.C.V.P.
Master's Degree in Chemical Research and Industrial Chemistry
Defense date
07.18.2024 09:00
07.18.2024 09:00
Summary
The main objective of this project is to be integrated in Nanfor's quality control department to learn about its core activities and analysis procedures. The objectives include understanding and actively participating in the tests carried out in the department. In the first part of this project, the company is presented, contextualising its history and describing the types of raw materials and feed it manufactures. In addition, its operation is detailed, and an exhaustive study of quality is carried out, going in depth into the different certifications that distinguish the company in this field. The second part focuses on the study of the different techniques used daily in the laboratory, both from a theoretical and experimental point of view. A complete understanding of the methods and the importance of the analyses to guarantee quality within the company is sought.
The main objective of this project is to be integrated in Nanfor's quality control department to learn about its core activities and analysis procedures. The objectives include understanding and actively participating in the tests carried out in the department. In the first part of this project, the company is presented, contextualising its history and describing the types of raw materials and feed it manufactures. In addition, its operation is detailed, and an exhaustive study of quality is carried out, going in depth into the different certifications that distinguish the company in this field. The second part focuses on the study of the different techniques used daily in the laboratory, both from a theoretical and experimental point of view. A complete understanding of the methods and the importance of the analyses to guarantee quality within the company is sought.
Direction
ABOAL SOMOZA, MANUEL (Tutorships)
Señarís Fraga, Natalia (Co-tutorships)
ABOAL SOMOZA, MANUEL (Tutorships)
Señarís Fraga, Natalia (Co-tutorships)
Court
Sanmartin Matalobos, Jesus (Coordinator)
SOTO CASTINHEIRA, MANUEL (Chairman)
BELLO BUGALLO, PASTORA MARIA (Secretary)
Leao Martins, José Manuel (Member)
Sanmartin Matalobos, Jesus (Coordinator)
SOTO CASTINHEIRA, MANUEL (Chairman)
BELLO BUGALLO, PASTORA MARIA (Secretary)
Leao Martins, José Manuel (Member)
Photooxidation of Heavy Metals by Atomic Quantum Cluster
Authorship
L.D.C.G.B.
Master's Degree in Chemical Research and Industrial Chemistry
L.D.C.G.B.
Master's Degree in Chemical Research and Industrial Chemistry
Defense date
07.18.2024 09:00
07.18.2024 09:00
Summary
Industrial wastewater represents one of the primary global sources of pollution due to the persistent presence of heavy metals and emerging contaminants such as Cr(VI) and BPA, even after conventional treatments. This complex and highly toxic composition underscores the urgent need for developing additional treatments enabling the effective removal of these pollutants through simultaneous oxidation and reduction processes within a redox system. This study focuses on the photocatalytic reduction of hexavalent chromium Cr (VI) using AQCs made of a few silver atoms, Ag M-M, supported on TiO2, which alter the electronic configuration of TiO2 , thereby enhancing the efficiency of the photocatalytic process. This approach highlights the potential of AgMM@TiO2 catalysts in Cr (VI) reduction, emphasizing the critical role of hole scavengers like BPA in improving photocatalytic efficiency. These findings provide a robust foundation for further research aimed at optimizing photocatalysis as an effective strategy in remediating industrial wastewater contaminated with heavy metals.
Industrial wastewater represents one of the primary global sources of pollution due to the persistent presence of heavy metals and emerging contaminants such as Cr(VI) and BPA, even after conventional treatments. This complex and highly toxic composition underscores the urgent need for developing additional treatments enabling the effective removal of these pollutants through simultaneous oxidation and reduction processes within a redox system. This study focuses on the photocatalytic reduction of hexavalent chromium Cr (VI) using AQCs made of a few silver atoms, Ag M-M, supported on TiO2, which alter the electronic configuration of TiO2 , thereby enhancing the efficiency of the photocatalytic process. This approach highlights the potential of AgMM@TiO2 catalysts in Cr (VI) reduction, emphasizing the critical role of hole scavengers like BPA in improving photocatalytic efficiency. These findings provide a robust foundation for further research aimed at optimizing photocatalysis as an effective strategy in remediating industrial wastewater contaminated with heavy metals.
Direction
VAZQUEZ VAZQUEZ, CARLOS (Tutorships)
BUCETA FERNANDEZ, DAVID (Co-tutorships)
VAZQUEZ VAZQUEZ, CARLOS (Tutorships)
BUCETA FERNANDEZ, DAVID (Co-tutorships)
Court
Sanmartin Matalobos, Jesus (Coordinator)
SOTO CASTINHEIRA, MANUEL (Chairman)
BELLO BUGALLO, PASTORA MARIA (Secretary)
Leao Martins, José Manuel (Member)
Sanmartin Matalobos, Jesus (Coordinator)
SOTO CASTINHEIRA, MANUEL (Chairman)
BELLO BUGALLO, PASTORA MARIA (Secretary)
Leao Martins, José Manuel (Member)
Validation of an autofluorescence model for the early aggregation of amyloid peptides
Authorship
J.S.C.
Master in Chemistry at the Interface of Biology and Materials Science
J.S.C.
Master in Chemistry at the Interface of Biology and Materials Science
Defense date
02.12.2023 10:00
02.12.2023 10:00
Summary
Amyloids, composed of aggregated proteins, are associated with neurodegenerative diseases like Alzheimer's and Parkinson's. Early detection of Alzheimer's disease poses a challenge due to its subtle symptoms, often mistaken for normal aging or other medical conditions. Amyloid aggregation state on each person can be a marker to its suffering from Alzheimer's disease on the early stages. Given that both Ab40 and Ab42 (the two most common amyloids) have naturally fluorescent amino-acids, this work has the aim of being a preliminary study on the use of amyloids autofluorescence for the determination of its own aggregation state. This study was centered on the use of Ab40 intrinsic fluorescence to determine its aggregation fraction. With this method, an easier way of study was also achieved, as not only the original amyloid without an external fluorophore attached can be used, but also only an adequate fluorimeter is needed, which is present in most laboratories. This study found significant differences on the fluorescence of aggregated and monomeric Ab40. The first found difference was a change on the tyrosine emission, that emits around 350 nm when amyloids are on monomeric state, due to suffering excited state ionization, while when Ab40 is aggregated, tyrosine has its usual emission around 300 nm. The other important change observed on emission was the presence of a band at 520 nm that only appeared with aggregates. Ratiometric fluorescence was also proved to be useful to determine the Ab40 aggregation state, in combination with the study of the short-wavelength emission peak position. Finally, a mechanism for the photophysical behavior of the Ab40 amyloids has been proposed, that is able to explain all the behaviors observed on the experiments.
Amyloids, composed of aggregated proteins, are associated with neurodegenerative diseases like Alzheimer's and Parkinson's. Early detection of Alzheimer's disease poses a challenge due to its subtle symptoms, often mistaken for normal aging or other medical conditions. Amyloid aggregation state on each person can be a marker to its suffering from Alzheimer's disease on the early stages. Given that both Ab40 and Ab42 (the two most common amyloids) have naturally fluorescent amino-acids, this work has the aim of being a preliminary study on the use of amyloids autofluorescence for the determination of its own aggregation state. This study was centered on the use of Ab40 intrinsic fluorescence to determine its aggregation fraction. With this method, an easier way of study was also achieved, as not only the original amyloid without an external fluorophore attached can be used, but also only an adequate fluorimeter is needed, which is present in most laboratories. This study found significant differences on the fluorescence of aggregated and monomeric Ab40. The first found difference was a change on the tyrosine emission, that emits around 350 nm when amyloids are on monomeric state, due to suffering excited state ionization, while when Ab40 is aggregated, tyrosine has its usual emission around 300 nm. The other important change observed on emission was the presence of a band at 520 nm that only appeared with aggregates. Ratiometric fluorescence was also proved to be useful to determine the Ab40 aggregation state, in combination with the study of the short-wavelength emission peak position. Finally, a mechanism for the photophysical behavior of the Ab40 amyloids has been proposed, that is able to explain all the behaviors observed on the experiments.
Direction
Rodríguez Prieto, María de la Flor (Tutorships)
NOVO RODRIGUEZ, MARIA DE LA MERCED (Co-tutorships)
Rodríguez Prieto, María de la Flor (Tutorships)
NOVO RODRIGUEZ, MARIA DE LA MERCED (Co-tutorships)
Court
RIVADULLA FERNANDEZ, JOSE FRANCISCO (Chairman)
NAPPI , MANUEL (Secretary)
PELAZ GARCIA, BEATRIZ (Member)
RIVADULLA FERNANDEZ, JOSE FRANCISCO (Chairman)
NAPPI , MANUEL (Secretary)
PELAZ GARCIA, BEATRIZ (Member)
Assessing the synthesis parameters for scale-up of biomimetic cell membrane nanoparticles in advancing drug delivery
Authorship
F.J.
Master in Chemistry at the Interface of Biology and Materials Science
F.J.
Master in Chemistry at the Interface of Biology and Materials Science
Defense date
02.12.2023 10:00
02.12.2023 10:00
Summary
Within the realm of such nano drug delivery vehicles, biomimetic nanoparticles have emerged as a fast-rising class of nanoparticles (NPs) that amalgamate the functional characteristic of biological materials with the pliability of synthetic materials to attain advantageous effects in complex biological systems. One such type of biomimetic nanoparticle is nanovesicles derived from cell membrane structures. These endogenous biomaterial source, are instrumental in designing advanced delivery systems. A noteworthy advancement in this domain is the emergence of cancer cell derived biomimetic nanoparticles, referred to as cellsomes, which hold immense potential for targeted drug delivery and cancer therapy. Scaling up the synthetic processes for these biomimetic cell membrane nanoparticles presents a formidable challenge, particularly concerning their application in targeted drug delivery and cancer therapy. This research project seeks to address this challenge by delving into the intricacies of scaling up nanoparticles derived specifically from cancer cells. This project carefully evaluates the potential of the gas-aided jacketed liposome extruder, analysing synthesis parameters impacting the scale-up of cellsomes nanovesicles for drug delivery applications. The critical synthesis parameters under investigation include pressure, yield, concentration, particle size, and drug loading efficiency. By systematically investigating these factors, the research aims to optimize the scale-up process, overcoming the inherent complexities associated with biological systems and molecular stability. Insights derived from this research are expected to furnish valuable knowledge on optimizing the synthesis process, thereby laying the groundwork for the larger-scale production of these biomimetic nanoparticles. This research endeavour to bridge the gap between the laboratory and clinical applications. The goal is to translate the optimized synthesis process into scalable production methodologies, facilitating the seamless integration of cellsomes into potential clinical applications in targeted and efficient drug delivery.
Within the realm of such nano drug delivery vehicles, biomimetic nanoparticles have emerged as a fast-rising class of nanoparticles (NPs) that amalgamate the functional characteristic of biological materials with the pliability of synthetic materials to attain advantageous effects in complex biological systems. One such type of biomimetic nanoparticle is nanovesicles derived from cell membrane structures. These endogenous biomaterial source, are instrumental in designing advanced delivery systems. A noteworthy advancement in this domain is the emergence of cancer cell derived biomimetic nanoparticles, referred to as cellsomes, which hold immense potential for targeted drug delivery and cancer therapy. Scaling up the synthetic processes for these biomimetic cell membrane nanoparticles presents a formidable challenge, particularly concerning their application in targeted drug delivery and cancer therapy. This research project seeks to address this challenge by delving into the intricacies of scaling up nanoparticles derived specifically from cancer cells. This project carefully evaluates the potential of the gas-aided jacketed liposome extruder, analysing synthesis parameters impacting the scale-up of cellsomes nanovesicles for drug delivery applications. The critical synthesis parameters under investigation include pressure, yield, concentration, particle size, and drug loading efficiency. By systematically investigating these factors, the research aims to optimize the scale-up process, overcoming the inherent complexities associated with biological systems and molecular stability. Insights derived from this research are expected to furnish valuable knowledge on optimizing the synthesis process, thereby laying the groundwork for the larger-scale production of these biomimetic nanoparticles. This research endeavour to bridge the gap between the laboratory and clinical applications. The goal is to translate the optimized synthesis process into scalable production methodologies, facilitating the seamless integration of cellsomes into potential clinical applications in targeted and efficient drug delivery.
Direction
DEL PINO GONZALEZ DE LA HIGUERA, PABLO ALFONSO (Tutorships)
DEL PINO GONZALEZ DE LA HIGUERA, PABLO ALFONSO (Tutorships)
Court
RIVADULLA FERNANDEZ, JOSE FRANCISCO (Chairman)
NAPPI , MANUEL (Secretary)
PELAZ GARCIA, BEATRIZ (Member)
RIVADULLA FERNANDEZ, JOSE FRANCISCO (Chairman)
NAPPI , MANUEL (Secretary)
PELAZ GARCIA, BEATRIZ (Member)
Content of plastics additives, phthalates and bisphenol in bivalve mollusk samples from the Galician estuaries
Authorship
A.P.C.
Master's Degree in Chemical Research and Industrial Chemistry
A.P.C.
Master's Degree in Chemical Research and Industrial Chemistry
Defense date
07.18.2024 09:00
07.18.2024 09:00
Summary
Phthalates and bisphenol compounds are additives widely used in the manufacture of plastic objects that provide specific properties improving the performance, stability or durability of the plastic. Many studies indicate that exposure to these compounds can be harmful to humans and ecosystems. Due to this, the need arises to optimize methods for the determination of these compounds in different environmental and food samples, to investigate their content in order to know if they are a risk to human health and to develop legislation to control exposure to these pollutants. The aim of this project is know the content of phthalate and bisphenol compounds in samples of several species of bivalve mollusks from the Galician estuaries by the application of two already optimized and validated methods based on the miniaturization of the MSPD (Matrix Solid Phase Dispersión). A comparative study was carried out on concentrations found in the different species studied and the area of origin (estuaries). Subsequently, a human health risk assessment was carried out.
Phthalates and bisphenol compounds are additives widely used in the manufacture of plastic objects that provide specific properties improving the performance, stability or durability of the plastic. Many studies indicate that exposure to these compounds can be harmful to humans and ecosystems. Due to this, the need arises to optimize methods for the determination of these compounds in different environmental and food samples, to investigate their content in order to know if they are a risk to human health and to develop legislation to control exposure to these pollutants. The aim of this project is know the content of phthalate and bisphenol compounds in samples of several species of bivalve mollusks from the Galician estuaries by the application of two already optimized and validated methods based on the miniaturization of the MSPD (Matrix Solid Phase Dispersión). A comparative study was carried out on concentrations found in the different species studied and the area of origin (estuaries). Subsequently, a human health risk assessment was carried out.
Direction
PEÑA VAZQUEZ, ELENA MARIA (Tutorships)
Carro Mariño, Maria de las Nieves (Co-tutorships)
PEÑA VAZQUEZ, ELENA MARIA (Tutorships)
Carro Mariño, Maria de las Nieves (Co-tutorships)
Court
Sanmartin Matalobos, Jesus (Coordinator)
SOTO CASTINHEIRA, MANUEL (Chairman)
BELLO BUGALLO, PASTORA MARIA (Secretary)
Leao Martins, José Manuel (Member)
Sanmartin Matalobos, Jesus (Coordinator)
SOTO CASTINHEIRA, MANUEL (Chairman)
BELLO BUGALLO, PASTORA MARIA (Secretary)
Leao Martins, José Manuel (Member)
Recognition of DNA Holliday junctions by cyclopeptides and peptide helicates
Authorship
A.J.B.
Master's Degree in Chemical Research and Industrial Chemistry
A.J.B.
Master's Degree in Chemical Research and Industrial Chemistry
Defense date
07.18.2024 09:00
07.18.2024 09:00
Summary
DNA is one of the most important biological targets for anticancer drugs, and the development of new chemical systems capable of its selective recognition is a hot topic in biological chemistry. Its best-known conformation is the canonical duplex structure (B-DNA), but this arrangement is usually present when DNA is not involved in any molecular process. When this is the case, non-canonical structures are formed. In this context, four-way junctions, or Holliday junctions (4WJs), are one of the most important non-canonical DNA structures. They are dynamic and fluctuate between an open and a closed conformation, with the former being the biologically active one. 4WJs are formed transiently during DNA insertion, recombination and repair processes, which are deregulated in cancer cells. The development of chemical systems capable of selectively recognizing these non-canonical structures within the cell nucleus is a critical objective, as it could subsequently allow efficient interference in the functioning of these cellular processes and, therefore, provide a new battery of anticancer drugs with an alternative mechanism of action. In this Master Thesis we describe the development of a new family of selective 4WJ recognition agents based on cyclopeptides and peptide helicates derived from the T4Ff motif. After their structural characterization by mass spectrometry and nuclear magnetic resonance, the study of their selective 4WJ recognition properties was carried out by fluorescence spectroscopy.
DNA is one of the most important biological targets for anticancer drugs, and the development of new chemical systems capable of its selective recognition is a hot topic in biological chemistry. Its best-known conformation is the canonical duplex structure (B-DNA), but this arrangement is usually present when DNA is not involved in any molecular process. When this is the case, non-canonical structures are formed. In this context, four-way junctions, or Holliday junctions (4WJs), are one of the most important non-canonical DNA structures. They are dynamic and fluctuate between an open and a closed conformation, with the former being the biologically active one. 4WJs are formed transiently during DNA insertion, recombination and repair processes, which are deregulated in cancer cells. The development of chemical systems capable of selectively recognizing these non-canonical structures within the cell nucleus is a critical objective, as it could subsequently allow efficient interference in the functioning of these cellular processes and, therefore, provide a new battery of anticancer drugs with an alternative mechanism of action. In this Master Thesis we describe the development of a new family of selective 4WJ recognition agents based on cyclopeptides and peptide helicates derived from the T4Ff motif. After their structural characterization by mass spectrometry and nuclear magnetic resonance, the study of their selective 4WJ recognition properties was carried out by fluorescence spectroscopy.
Direction
VAZQUEZ LOPEZ, MIGUEL (Tutorships)
Granja Guillán, Juan Ramón (Co-tutorships)
VAZQUEZ LOPEZ, MIGUEL (Tutorships)
Granja Guillán, Juan Ramón (Co-tutorships)
Court
Sanmartin Matalobos, Jesus (Coordinator)
Valencia Matarranz, Laura Mª (Chairman)
FERNANDEZ TRILLO, FRANCISCO (Secretary)
GONZALEZ NOYA, ANA MARIA (Member)
Sanmartin Matalobos, Jesus (Coordinator)
Valencia Matarranz, Laura Mª (Chairman)
FERNANDEZ TRILLO, FRANCISCO (Secretary)
GONZALEZ NOYA, ANA MARIA (Member)
Synthesis of chiral ligands and application to the enantioselective activation of C-H bonds by catalysis with palladium complexes
Authorship
D.C.T.
Master in Organic Chemistry (3ª ed)
D.C.T.
Master in Organic Chemistry (3ª ed)
Defense date
07.18.2024 09:00
07.18.2024 09:00
Summary
Transition metal-catalyzed C-H bond functionalization represents an important methodology for constructing relevant and complex scaffolds. In the las two decades one of the main goals is performing these transformations under milder conditions, increasing the complexity, efficiency and achieving enantioselective. The primary impetus for advancing enantioselective C-H activation has been the development of chiral ligands. These ligands bind to transition metal catalysts, creating a steric environment that enables stereocontrol and enhances the catalyst's reactivity. The preferred ligands in asymmetric palladium-catalyzed C-H activation are MPAAs (mono-N-protected amino acids). However, due to their geometric flexibility, the chiral induction is not always optimal. To address this issue, new ligands such as NOBINAc have been developed in recent years. NOBINAc ligands combine the axial chirality of binaphthyl scaffolds with the bifunctional and bidentate coordination properties of MPAAs. The objective of this work is to develop and synthesize two new types of ligands. Firstly, derivatives of NOBINAc have been designed and synthesized with various substitutions on the ring and modifications to the protecting group. Secondly, a new type of ligands called MAMPO (mono-N-protected aminophenol ligands) has been developed. These ligands feature point chirality and exhibit bifunctionality and bidentate coordination. Both types of ligands were applied to different enantioselective palladium-catalyzed C-H activation reactions.
Transition metal-catalyzed C-H bond functionalization represents an important methodology for constructing relevant and complex scaffolds. In the las two decades one of the main goals is performing these transformations under milder conditions, increasing the complexity, efficiency and achieving enantioselective. The primary impetus for advancing enantioselective C-H activation has been the development of chiral ligands. These ligands bind to transition metal catalysts, creating a steric environment that enables stereocontrol and enhances the catalyst's reactivity. The preferred ligands in asymmetric palladium-catalyzed C-H activation are MPAAs (mono-N-protected amino acids). However, due to their geometric flexibility, the chiral induction is not always optimal. To address this issue, new ligands such as NOBINAc have been developed in recent years. NOBINAc ligands combine the axial chirality of binaphthyl scaffolds with the bifunctional and bidentate coordination properties of MPAAs. The objective of this work is to develop and synthesize two new types of ligands. Firstly, derivatives of NOBINAc have been designed and synthesized with various substitutions on the ring and modifications to the protecting group. Secondly, a new type of ligands called MAMPO (mono-N-protected aminophenol ligands) has been developed. These ligands feature point chirality and exhibit bifunctionality and bidentate coordination. Both types of ligands were applied to different enantioselective palladium-catalyzed C-H activation reactions.
Direction
GULIAS COSTA, MOISES (Tutorships)
GULIAS COSTA, MOISES (Tutorships)
Court
VARELA CARRETE, JESUS ANGEL (Chairman)
Vela Gallego, Sonia (Secretary)
Martínez del Campo, Teresa (Member)
VARELA CARRETE, JESUS ANGEL (Chairman)
Vela Gallego, Sonia (Secretary)
Martínez del Campo, Teresa (Member)
Synthesis of delta-amino acids for the creation of supramolecular structures: Nanotubes, dimers and capsules.
Authorship
R.F.L.
Master in Organic Chemistry (3ª ed)
R.F.L.
Master in Organic Chemistry (3ª ed)
Defense date
07.18.2024 09:00
07.18.2024 09:00
Summary
In the present project, the synthesis of tripeptide Boc-D-Tyr(OMe)-MeN-delta-Ach-L-MeN-Ala-OFm and the optimization of the synthesis of the methyl ester of (1R,3R,4R)-4-azido-3-hydroxy cyclohexanecarboxylic acid were carried out. Both compounds are precursors of an alfa,delta-cyclopeptide (CP) capable of forming supramolecular dimers through a self-assembly process. The novel characteristic of this CP is the presence of three hydroxyl groups that will be oriented toward the internal cavity of the supramolecular dimer. This hydroxyl group would allow other functionalizations and the possibility of encapsulating polar molecules such as amino acids, oligosaccharides, nucleic acids... The tetrapeptide Cbz-D-Leu-tBuOAcN-delta-Ach-L-MeN-Ala-delta-Ach-OMe was also synthesized. This compound is the precursor of an alfa,delta-cyclopeptide to which a subphthalocyanine cap will be attached to create a novel peptide capsule with a large hydrophobic internal cavity that will be used to encapsulate fullerene derivatives.
In the present project, the synthesis of tripeptide Boc-D-Tyr(OMe)-MeN-delta-Ach-L-MeN-Ala-OFm and the optimization of the synthesis of the methyl ester of (1R,3R,4R)-4-azido-3-hydroxy cyclohexanecarboxylic acid were carried out. Both compounds are precursors of an alfa,delta-cyclopeptide (CP) capable of forming supramolecular dimers through a self-assembly process. The novel characteristic of this CP is the presence of three hydroxyl groups that will be oriented toward the internal cavity of the supramolecular dimer. This hydroxyl group would allow other functionalizations and the possibility of encapsulating polar molecules such as amino acids, oligosaccharides, nucleic acids... The tetrapeptide Cbz-D-Leu-tBuOAcN-delta-Ach-L-MeN-Ala-delta-Ach-OMe was also synthesized. This compound is the precursor of an alfa,delta-cyclopeptide to which a subphthalocyanine cap will be attached to create a novel peptide capsule with a large hydrophobic internal cavity that will be used to encapsulate fullerene derivatives.
Direction
AMORIN LOPEZ, MANUEL (Tutorships)
Granja Guillán, Juan Ramón (Co-tutorships)
AMORIN LOPEZ, MANUEL (Tutorships)
Granja Guillán, Juan Ramón (Co-tutorships)
Court
VARELA CARRETE, JESUS ANGEL (Chairman)
Vela Gallego, Sonia (Secretary)
Martínez del Campo, Teresa (Member)
VARELA CARRETE, JESUS ANGEL (Chairman)
Vela Gallego, Sonia (Secretary)
Martínez del Campo, Teresa (Member)
Study of microphysiological systems (organs on a chip, OOAC) to evaluate the toxicity of NPs in foods
Authorship
O.J.M.
Master's Degree in Chemical Research and Industrial Chemistry
O.J.M.
Master's Degree in Chemical Research and Industrial Chemistry
Defense date
07.18.2024 09:00
07.18.2024 09:00
Summary
Currently, the use of nanoparticles (NPs) and nanomaterials (NMs) is constantly expanding in various industrial sectors. The increase in the application of silver (Ag) and titanium dioxide (TiO2) nanoparticles in food processing and packaging is notable, which poses a new route of exposure to these particles in our body. Therefore, there is a pressing need to evaluate the possible toxicological risks associated with the use of nanoparticles in these products, through in vitro studies prior to conducting in vivo toxicity tests. The in vitro gastrointestinal digestion models used to date present limitations in accurately reproducing intestinal physiology. In this context, an emerging field has developed: microphysiological systems, also known as 'organs-on-a-chip' (OoC), which allow for more precise recreation of the physiological conditions of various cells. In this research, the study of the bioavailability of silver nanoparticles (Ag NPs) and titanium dioxide nanoparticles (TiO2 NPs) in food additives E-171 (TiO2-based) and E-174 (silver-based) was addressed using an organs-on-a-chip system. It was observed that TiO2 NPs have greater bioaccessibility than Ag NPs, although with a high margin of error. In both cases, the sample type does not affect bioaccessibility. On the other hand, TiO2 NPs are less bioavailable than Ag NPs, which vary depending on the sample.
Currently, the use of nanoparticles (NPs) and nanomaterials (NMs) is constantly expanding in various industrial sectors. The increase in the application of silver (Ag) and titanium dioxide (TiO2) nanoparticles in food processing and packaging is notable, which poses a new route of exposure to these particles in our body. Therefore, there is a pressing need to evaluate the possible toxicological risks associated with the use of nanoparticles in these products, through in vitro studies prior to conducting in vivo toxicity tests. The in vitro gastrointestinal digestion models used to date present limitations in accurately reproducing intestinal physiology. In this context, an emerging field has developed: microphysiological systems, also known as 'organs-on-a-chip' (OoC), which allow for more precise recreation of the physiological conditions of various cells. In this research, the study of the bioavailability of silver nanoparticles (Ag NPs) and titanium dioxide nanoparticles (TiO2 NPs) in food additives E-171 (TiO2-based) and E-174 (silver-based) was addressed using an organs-on-a-chip system. It was observed that TiO2 NPs have greater bioaccessibility than Ag NPs, although with a high margin of error. In both cases, the sample type does not affect bioaccessibility. On the other hand, TiO2 NPs are less bioavailable than Ag NPs, which vary depending on the sample.
Direction
MOREDA PIÑEIRO, ANTONIO (Tutorships)
Domínguez González, María Raquel (Co-tutorships)
MOREDA PIÑEIRO, ANTONIO (Tutorships)
Domínguez González, María Raquel (Co-tutorships)
Court
Sanmartin Matalobos, Jesus (Coordinator)
YEBRA BIURRUN, MARIA DEL CARMEN (Chairman)
Prieto Jiménez, Inmaculada (Secretary)
Carlosena Zubieta, Alatzne (Member)
Sanmartin Matalobos, Jesus (Coordinator)
YEBRA BIURRUN, MARIA DEL CARMEN (Chairman)
Prieto Jiménez, Inmaculada (Secretary)
Carlosena Zubieta, Alatzne (Member)
Development and application of an analytical methodology for the determination of herbicides in agricultural soils
Authorship
A.B.S.
Master's Degree in Chemical Research and Industrial Chemistry
A.B.S.
Master's Degree in Chemical Research and Industrial Chemistry
Defense date
07.18.2024 09:00
07.18.2024 09:00
Summary
The study of the environmental impact of herbicides has been under investigation for years, due to data of their presence in many environmental matrices, and their potential effects on non-target organisms. Both administration and the chemical industry continuously review the list of authorized compounds for application and develop new formulations that are theoretically more effective against target organisms, and more selective. In summary, the trend is to have a suite of effective herbicides for the control of unwanted vegetation, while limiting their persistence in environmental conditions, their migration to other compartments (different from the topsoil layer), and their effects on other organisms. In this study, an analytical procedure for extracting herbicides from different chemical families in agricultural soil samples was optimized and validated. After that, the developed method was applied to study their distribution in vineyard soils collected from different Designations of Origin or sub-regions, both in Galicia and La Rioja, at different times of the year. The selection of herbicides includes compounds whose use is authorized, as well as others that have lost their authorization but may persist in agricultural soils. The main objective of the study is to detect the presence and persistence of these compounds in the soils of the different plots considered. The list of selected compounds does not include ionic herbicides, such as glyphosate, whose analysis requires separation conditions different from those used in reversed-phase liquid chromatography, which was employed in this study.
The study of the environmental impact of herbicides has been under investigation for years, due to data of their presence in many environmental matrices, and their potential effects on non-target organisms. Both administration and the chemical industry continuously review the list of authorized compounds for application and develop new formulations that are theoretically more effective against target organisms, and more selective. In summary, the trend is to have a suite of effective herbicides for the control of unwanted vegetation, while limiting their persistence in environmental conditions, their migration to other compartments (different from the topsoil layer), and their effects on other organisms. In this study, an analytical procedure for extracting herbicides from different chemical families in agricultural soil samples was optimized and validated. After that, the developed method was applied to study their distribution in vineyard soils collected from different Designations of Origin or sub-regions, both in Galicia and La Rioja, at different times of the year. The selection of herbicides includes compounds whose use is authorized, as well as others that have lost their authorization but may persist in agricultural soils. The main objective of the study is to detect the presence and persistence of these compounds in the soils of the different plots considered. The list of selected compounds does not include ionic herbicides, such as glyphosate, whose analysis requires separation conditions different from those used in reversed-phase liquid chromatography, which was employed in this study.
Direction
RODRIGUEZ PEREIRO, ISAAC (Tutorships)
RAMIL CRIADO, MARIA (Co-tutorships)
RODRIGUEZ PEREIRO, ISAAC (Tutorships)
RAMIL CRIADO, MARIA (Co-tutorships)
Court
Sanmartin Matalobos, Jesus (Coordinator)
YEBRA BIURRUN, MARIA DEL CARMEN (Chairman)
Prieto Jiménez, Inmaculada (Secretary)
Carlosena Zubieta, Alatzne (Member)
Sanmartin Matalobos, Jesus (Coordinator)
YEBRA BIURRUN, MARIA DEL CARMEN (Chairman)
Prieto Jiménez, Inmaculada (Secretary)
Carlosena Zubieta, Alatzne (Member)
Thiosemicarbazone ligands functionalized with iminophosphorane groups.
Authorship
M.D.L.F.M.A.
Master's Degree in Chemical Research and Industrial Chemistry
M.D.L.F.M.A.
Master's Degree in Chemical Research and Industrial Chemistry
Defense date
07.18.2024 09:00
07.18.2024 09:00
Summary
Thiosemicarbazones are organosulfur compounds that possess an imine bond, while iminophosphoranes are organic compounds with the general composition R3PNR. The ease of varying the molecular structures of thiosemicarbazones has expanded their utility as ligands because additional donor groups can be added to provide greater stability to metal complexes through the formation of chelate rings. Despite this, derivatives of this type functionalized with iminophosphorane groups have never been synthesized. In this work, two thiosemicarbazone ligands functionalized with iminophosphorane were synthesized, containing two (N, N, S) coordination domains connected through a flexible spacer (flexible ligand) and a rigid spacer (rigid ligand). These ligands were used to obtain polynuclear metal complexes. The synthesis of the ligands was carried out in three stages. It began with the synthesis of the precursor 4,4'-diazidodiphenylmethane and 1,3-diazidobenzene by reacting 4,4'-diaminodiphenylmethane and 1,3-diaminobenzene with sodium azide. The precursor (2-(diphenylphosphino)benzyl)-N-methylthiosemicarbazone was obtained by reacting 2-diphenylphosphinobenzaldehyde with 4-methyl-3-thiosemicarbazide, and finally, they were condensed via the Staudinger reaction. Coordination compounds of copper, zinc, palladium, and ruthenium with the synthesized bis(thiosemicarbazone-iminophosphorane) ligands were sought to study their behavior as ligands. It was found that in the case of copper, both the rigid and flexible ligands coordinate as ionic ligands, occurring in the presence and/or absence of the coligand dppe. For zinc, neither of the ligands coordinates to the metal. Palladium does not coordinate with the flexible ligand; only a mixture of the ligand with palladium (0) particles is obtained, but with the rigid ligand, it coordinates as a neutral ligand. The flexible ligand coordinates ionically to ruthenium, while the rigid ligand coordinates in its neutral form. In all cases, the rigid and flexible ligands, whether free and/or coordinated, show a tendency to hydrolyze, as evidenced by the signals of the phosphine-thiosemicarbazone oxide in the obtained solids. The structures of any of the obtained complexes could not be confirmed as the appropriate recrystallization conditions were not found.
Thiosemicarbazones are organosulfur compounds that possess an imine bond, while iminophosphoranes are organic compounds with the general composition R3PNR. The ease of varying the molecular structures of thiosemicarbazones has expanded their utility as ligands because additional donor groups can be added to provide greater stability to metal complexes through the formation of chelate rings. Despite this, derivatives of this type functionalized with iminophosphorane groups have never been synthesized. In this work, two thiosemicarbazone ligands functionalized with iminophosphorane were synthesized, containing two (N, N, S) coordination domains connected through a flexible spacer (flexible ligand) and a rigid spacer (rigid ligand). These ligands were used to obtain polynuclear metal complexes. The synthesis of the ligands was carried out in three stages. It began with the synthesis of the precursor 4,4'-diazidodiphenylmethane and 1,3-diazidobenzene by reacting 4,4'-diaminodiphenylmethane and 1,3-diaminobenzene with sodium azide. The precursor (2-(diphenylphosphino)benzyl)-N-methylthiosemicarbazone was obtained by reacting 2-diphenylphosphinobenzaldehyde with 4-methyl-3-thiosemicarbazide, and finally, they were condensed via the Staudinger reaction. Coordination compounds of copper, zinc, palladium, and ruthenium with the synthesized bis(thiosemicarbazone-iminophosphorane) ligands were sought to study their behavior as ligands. It was found that in the case of copper, both the rigid and flexible ligands coordinate as ionic ligands, occurring in the presence and/or absence of the coligand dppe. For zinc, neither of the ligands coordinates to the metal. Palladium does not coordinate with the flexible ligand; only a mixture of the ligand with palladium (0) particles is obtained, but with the rigid ligand, it coordinates as a neutral ligand. The flexible ligand coordinates ionically to ruthenium, while the rigid ligand coordinates in its neutral form. In all cases, the rigid and flexible ligands, whether free and/or coordinated, show a tendency to hydrolyze, as evidenced by the signals of the phosphine-thiosemicarbazone oxide in the obtained solids. The structures of any of the obtained complexes could not be confirmed as the appropriate recrystallization conditions were not found.
Direction
SOUSA PEDRARES, ANTONIO (Tutorships)
SOUSA PEDRARES, ANTONIO (Tutorships)
Court
Sanmartin Matalobos, Jesus (Coordinator)
Valencia Matarranz, Laura Mª (Chairman)
FERNANDEZ TRILLO, FRANCISCO (Secretary)
GONZALEZ NOYA, ANA MARIA (Member)
Sanmartin Matalobos, Jesus (Coordinator)
Valencia Matarranz, Laura Mª (Chairman)
FERNANDEZ TRILLO, FRANCISCO (Secretary)
GONZALEZ NOYA, ANA MARIA (Member)
Towards the synthesis of azulene-based nanographenes through organometallic catalysis and aryne chemistry
Authorship
A.B.M.
Master in Chemistry at the Interface of Biology and Materials Science
A.B.M.
Master in Chemistry at the Interface of Biology and Materials Science
Defense date
02.12.2023 10:00
02.12.2023 10:00
Summary
Interest in nanographene materials has grown in recent years, owing to their optoelectronic properties. These properties can be modified with the introduction of non-hexagonal rings in their structure such as azulene motifs. These structural modifications create the challenge of synthesizing such compounds to study their behaviour. In this regard, new bottom-up synthetic tools, such as metal-catalyzed C-H activation, can be useful for preparing complex structures from commercially available compounds of low molecular weight. In this project, we employed a route that makes use of a rhodium-catalyzed [3+2] annulation as the key step to synthesize small polycyclic aromatic hydrocarbons containing the azulene moiety and then explored its derivatization to prepare nanographenes.
Interest in nanographene materials has grown in recent years, owing to their optoelectronic properties. These properties can be modified with the introduction of non-hexagonal rings in their structure such as azulene motifs. These structural modifications create the challenge of synthesizing such compounds to study their behaviour. In this regard, new bottom-up synthetic tools, such as metal-catalyzed C-H activation, can be useful for preparing complex structures from commercially available compounds of low molecular weight. In this project, we employed a route that makes use of a rhodium-catalyzed [3+2] annulation as the key step to synthesize small polycyclic aromatic hydrocarbons containing the azulene moiety and then explored its derivatization to prepare nanographenes.
Direction
GULIAS COSTA, MOISES (Tutorships)
PEÑA GIL, DIEGO (Co-tutorships)
GULIAS COSTA, MOISES (Tutorships)
PEÑA GIL, DIEGO (Co-tutorships)
Court
RIVADULLA FERNANDEZ, JOSE FRANCISCO (Chairman)
NAPPI , MANUEL (Secretary)
PELAZ GARCIA, BEATRIZ (Member)
RIVADULLA FERNANDEZ, JOSE FRANCISCO (Chairman)
NAPPI , MANUEL (Secretary)
PELAZ GARCIA, BEATRIZ (Member)
New precision antibiotics through allosteric inhibition of the enzyme glutamate-5-kinase
Authorship
A.C.F.
Master in Organic Chemistry (3ª ed)
A.C.F.
Master in Organic Chemistry (3ª ed)
Defense date
09.13.2024 09:00
09.13.2024 09:00
Summary
Tuberculosis (TB) remains one of the leading causes of mortality worldwide. Despite the availability of existing treatments, the emergence of extensively drugresistant strains (XDR-TB), for which there are no effective therapeutic options, highlights the urgent need for new therapeutic approaches. Natural products have been instrumental in the discovery and development of new drugs, with many of these products, as well as semi-synthetic compounds, successfully making their way into clinical practice. In this context, our research group is focusing on the therapeutic potential of 3H-pyrrolo[2,3-c]quinolines as potential anti-TB agents. Recently, we identified two derivatives, compounds 8 and 9, which have shown excellent in vitro activity against M. tuberculosis. In this project, we synthesized a series of compounds, 10-19, inspired by the structural core of 3H-pyrrolo[2,3-c]quinolines. Analogues of compounds 8 and 9 were synthesized by chemical modification at different positions of the aromatic ring. This series of compounds will be tested in vitro to assess their therapeutic potential against M. tuberculosis.
Tuberculosis (TB) remains one of the leading causes of mortality worldwide. Despite the availability of existing treatments, the emergence of extensively drugresistant strains (XDR-TB), for which there are no effective therapeutic options, highlights the urgent need for new therapeutic approaches. Natural products have been instrumental in the discovery and development of new drugs, with many of these products, as well as semi-synthetic compounds, successfully making their way into clinical practice. In this context, our research group is focusing on the therapeutic potential of 3H-pyrrolo[2,3-c]quinolines as potential anti-TB agents. Recently, we identified two derivatives, compounds 8 and 9, which have shown excellent in vitro activity against M. tuberculosis. In this project, we synthesized a series of compounds, 10-19, inspired by the structural core of 3H-pyrrolo[2,3-c]quinolines. Analogues of compounds 8 and 9 were synthesized by chemical modification at different positions of the aromatic ring. This series of compounds will be tested in vitro to assess their therapeutic potential against M. tuberculosis.
Direction
GONZALEZ BELLO, CONCEPCION (Tutorships)
GONZALEZ BELLO, CONCEPCION (Tutorships)
Court
VARELA CARRETE, JESUS ANGEL (Chairman)
Vela Gallego, Sonia (Secretary)
Filippone , Salvatore (Member)
VARELA CARRETE, JESUS ANGEL (Chairman)
Vela Gallego, Sonia (Secretary)
Filippone , Salvatore (Member)
Fotooxidación de contaminantes farmacéuticos catalizada por Clústeres Cuánticos Atómicos
Authorship
F.O.H.
Master's Degree in Chemical Research and Industrial Chemistry
F.O.H.
Master's Degree in Chemical Research and Industrial Chemistry
Defense date
07.18.2024 09:00
07.18.2024 09:00
Summary
Emerging pollutants (EPs) are a concern for the environment because conventional water treatment methods are not capable of removing them. New technologies, such as advanced oxidation processes using TiO2-based photocatalysts, have shown photodegradative activity against various EPs, thus offering a solution to this problem as an alternative for water remediation. In this study, the application of a series of photocatalysts AgMM@TiO2 based on atomic quantum clusters (AQCs) developed by the company Nanogap, regarding a possible use in the photodegradation of diclofenac and ibuprofen will be evaluated. To investigate this, several photodegradation experiments were conducted to assess the impact of different catalysts and light sources on the degradation rate of the pollutants, including ultraviolet light (high-intensity UVC or UV-LED) and solar radiation (solar simulators). This was carried out by monitoring the evolution of the UV-Vis spectra of the pollutants through UV-Vis spectrophotometry and quantifying the amounts of remaining pollutants and degradation intermediates using high-performance liquid chromatography (HPLC). Based on the results of these experiments, it was confirmed that the presence of AQCs improved the degradation capabilities of the catalysts compared to TiO2. Experiments with ibuprofen showed degradation under solar simulation, indicating potential for future studies on solar photocatalysis. Additional studies will be conducted using HPLC or total organic carbon (TOC) analysis to consolidate these conclusions due to the concerning presence of recalcitrant intermediates with known toxicity.
Emerging pollutants (EPs) are a concern for the environment because conventional water treatment methods are not capable of removing them. New technologies, such as advanced oxidation processes using TiO2-based photocatalysts, have shown photodegradative activity against various EPs, thus offering a solution to this problem as an alternative for water remediation. In this study, the application of a series of photocatalysts AgMM@TiO2 based on atomic quantum clusters (AQCs) developed by the company Nanogap, regarding a possible use in the photodegradation of diclofenac and ibuprofen will be evaluated. To investigate this, several photodegradation experiments were conducted to assess the impact of different catalysts and light sources on the degradation rate of the pollutants, including ultraviolet light (high-intensity UVC or UV-LED) and solar radiation (solar simulators). This was carried out by monitoring the evolution of the UV-Vis spectra of the pollutants through UV-Vis spectrophotometry and quantifying the amounts of remaining pollutants and degradation intermediates using high-performance liquid chromatography (HPLC). Based on the results of these experiments, it was confirmed that the presence of AQCs improved the degradation capabilities of the catalysts compared to TiO2. Experiments with ibuprofen showed degradation under solar simulation, indicating potential for future studies on solar photocatalysis. Additional studies will be conducted using HPLC or total organic carbon (TOC) analysis to consolidate these conclusions due to the concerning presence of recalcitrant intermediates with known toxicity.
Direction
VAZQUEZ VAZQUEZ, CARLOS (Tutorships)
Rodríguez Arias, Iria (Co-tutorships)
VAZQUEZ VAZQUEZ, CARLOS (Tutorships)
Rodríguez Arias, Iria (Co-tutorships)
Court
Sanmartin Matalobos, Jesus (Coordinator)
SOTO CASTINHEIRA, MANUEL (Chairman)
BELLO BUGALLO, PASTORA MARIA (Secretary)
Leao Martins, José Manuel (Member)
Sanmartin Matalobos, Jesus (Coordinator)
SOTO CASTINHEIRA, MANUEL (Chairman)
BELLO BUGALLO, PASTORA MARIA (Secretary)
Leao Martins, José Manuel (Member)
Synthesis of superchaotropic boron clusters coupled to cargo molecules for transport through membranes.
Authorship
A.L.R.
Master in Organic Chemistry (3ª ed)
A.L.R.
Master in Organic Chemistry (3ª ed)
Defense date
07.18.2024 09:00
07.18.2024 09:00
Summary
The Montenegro Lab recently introduced the concept of using superchaotropic dodecaborate boron clusters for transporting a wide range of hydrophilic substances across lipid membranes and into cells. This transport is enabled by the superchaotropic properties of the cluster, which disrupt the hydrogen bonding network of water more effectively than standard chaotropic ions in the Hofmeister series. These carriers offers distinct advantages over their amphiphilic counterparts, including high water solubility, preventing aggregation, and great stability. Currently, these carriers operate through weak supramolecular interactions, which facilitate the release of the cargo within the cell. However, the exact mechanism and specificity of this transport, as well as the cargo capacity and potential for co-transport of other substances, remain unclear. To address this knowledge gap, this project aims to covalently attach a cargo molecule to the dodecaborate cluster, ensuring exclusive transport of the desired cargo. Two potential synthetic routes will be explored: the formation of a reversible ester bond between the cargo and the cluster, cleavable by intracellular esterases, and the formation of a triazole group using Copper(I)-catalyzed Azide-Alkyne Cycloaddition (CuAAC) Click Chemistry to link the cargo and the cluster.
The Montenegro Lab recently introduced the concept of using superchaotropic dodecaborate boron clusters for transporting a wide range of hydrophilic substances across lipid membranes and into cells. This transport is enabled by the superchaotropic properties of the cluster, which disrupt the hydrogen bonding network of water more effectively than standard chaotropic ions in the Hofmeister series. These carriers offers distinct advantages over their amphiphilic counterparts, including high water solubility, preventing aggregation, and great stability. Currently, these carriers operate through weak supramolecular interactions, which facilitate the release of the cargo within the cell. However, the exact mechanism and specificity of this transport, as well as the cargo capacity and potential for co-transport of other substances, remain unclear. To address this knowledge gap, this project aims to covalently attach a cargo molecule to the dodecaborate cluster, ensuring exclusive transport of the desired cargo. Two potential synthetic routes will be explored: the formation of a reversible ester bond between the cargo and the cluster, cleavable by intracellular esterases, and the formation of a triazole group using Copper(I)-catalyzed Azide-Alkyne Cycloaddition (CuAAC) Click Chemistry to link the cargo and the cluster.
Direction
MONTENEGRO GARCIA, JAVIER (Tutorships)
QUEME PEÑA, MAYRA MARITZA (Co-tutorships)
MONTENEGRO GARCIA, JAVIER (Tutorships)
QUEME PEÑA, MAYRA MARITZA (Co-tutorships)
Court
VARELA CARRETE, JESUS ANGEL (Chairman)
Vela Gallego, Sonia (Secretary)
Martínez del Campo, Teresa (Member)
VARELA CARRETE, JESUS ANGEL (Chairman)
Vela Gallego, Sonia (Secretary)
Martínez del Campo, Teresa (Member)
New Mechanisms of Conformational Communication in Macromolecular Gears based on Meta-substituted Chiral Poly(phenylacetylene)s
Authorship
B.H.V.
Master's Degree in Chemical Research and Industrial Chemistry
B.H.V.
Master's Degree in Chemical Research and Industrial Chemistry
Defense date
07.18.2024 09:30
07.18.2024 09:30
Summary
Stimuli-responsive chiral helical polymers usually bear a pendant group whose conformational composition can be altered by the presence of an external stimuli. This structural change at the pendant group led to a different spatial arrangement of the substituents at the chiral center that can result in a helix inversion, asymmetry amplification or helical excess depletion of the polymer. In this work, we show an unexplored conformational communication mechanism triggered by steric effects at the helical scaffold and where more than one bond is involved in a helix inversion process. Thus, by using three different meta-substituted PPAs, poly-[(S)-Val-(R)-MPA], m-poly-[(S)-Val-(S)-MPA] and m-poly-[(S)-Val-(S/R)-MPA], we demonstrate how variations in the conformational composition at the chiral pendant by solvent polarity or metal ions, triggers a second conformational change at the linker used to connect the chiral pendant and the poly(phenylacetylene). Moreover, while variations at the conformational composition in the pendant does not affect to the helical sense of the PPA, the subsequent rotation at the linker triggered to release the steric hindrance generated in the PPA results in a final helix inversion process. Thus, this work opens a new scenario to create stimuli responsive polymers based on complex adaptive conformational communication mechanisms.
Stimuli-responsive chiral helical polymers usually bear a pendant group whose conformational composition can be altered by the presence of an external stimuli. This structural change at the pendant group led to a different spatial arrangement of the substituents at the chiral center that can result in a helix inversion, asymmetry amplification or helical excess depletion of the polymer. In this work, we show an unexplored conformational communication mechanism triggered by steric effects at the helical scaffold and where more than one bond is involved in a helix inversion process. Thus, by using three different meta-substituted PPAs, poly-[(S)-Val-(R)-MPA], m-poly-[(S)-Val-(S)-MPA] and m-poly-[(S)-Val-(S/R)-MPA], we demonstrate how variations in the conformational composition at the chiral pendant by solvent polarity or metal ions, triggers a second conformational change at the linker used to connect the chiral pendant and the poly(phenylacetylene). Moreover, while variations at the conformational composition in the pendant does not affect to the helical sense of the PPA, the subsequent rotation at the linker triggered to release the steric hindrance generated in the PPA results in a final helix inversion process. Thus, this work opens a new scenario to create stimuli responsive polymers based on complex adaptive conformational communication mechanisms.
Direction
FREIRE IRIBARNE, FELIX MANUEL (Tutorships)
RODRIGUEZ RIEGO, RAFAEL (Co-tutorships)
FREIRE IRIBARNE, FELIX MANUEL (Tutorships)
RODRIGUEZ RIEGO, RAFAEL (Co-tutorships)
Court
Sanmartin Matalobos, Jesus (Coordinator)
CID FERNANDEZ, MARIA MAGDALENA (Chairman)
Bermúdez García, Juan Manuel (Secretary)
GULIAS COSTA, MOISES (Member)
Sanmartin Matalobos, Jesus (Coordinator)
CID FERNANDEZ, MARIA MAGDALENA (Chairman)
Bermúdez García, Juan Manuel (Secretary)
GULIAS COSTA, MOISES (Member)
Towards the enantioselective synthesis of Dictyopterene A via copper-catalyzed asymmetric allylboration of acetylene gas
Authorship
C.M.A.B.
Master in Organic Chemistry (3ª ed)
C.M.A.B.
Master in Organic Chemistry (3ª ed)
Defense date
07.18.2024 09:00
07.18.2024 09:00
Summary
Dictyopterene A is a natural product that belongs to a family of chemical compounds called dictyopterenes that can be found in marine and freshwater environments. Currently, there is a great interest in the development of new methodologies that allow the synthesis of this type of compounds. However, the previous synthetic strategies in this field usually involve multistep processes which are typically associated to low yields and selectivity. Recently, in our group we have developed methodologies for the copper-catalyzed enantioselective allylboration of alkynes to obtain versatile multifunctional building blocks. Based on this strategy, we envisioned that the use of acetylene gas as a starting material would produce an intermediate for the total synthesis of dictyopterene A. We here report the optimization of the asymmetric three-component coupling between acetylene, 1,4-dibromobutene and bis(pinacolato)diboron. Synthetic efforts to convert the resulting product into Dictyopterene A in a 2-step process are also presented.
Dictyopterene A is a natural product that belongs to a family of chemical compounds called dictyopterenes that can be found in marine and freshwater environments. Currently, there is a great interest in the development of new methodologies that allow the synthesis of this type of compounds. However, the previous synthetic strategies in this field usually involve multistep processes which are typically associated to low yields and selectivity. Recently, in our group we have developed methodologies for the copper-catalyzed enantioselective allylboration of alkynes to obtain versatile multifunctional building blocks. Based on this strategy, we envisioned that the use of acetylene gas as a starting material would produce an intermediate for the total synthesis of dictyopterene A. We here report the optimization of the asymmetric three-component coupling between acetylene, 1,4-dibromobutene and bis(pinacolato)diboron. Synthetic efforts to convert the resulting product into Dictyopterene A in a 2-step process are also presented.
Direction
FAÑANAS MASTRAL, MARTIN (Tutorships)
FAÑANAS MASTRAL, MARTIN (Tutorships)
Court
VARELA CARRETE, JESUS ANGEL (Chairman)
Vela Gallego, Sonia (Secretary)
Martínez del Campo, Teresa (Member)
VARELA CARRETE, JESUS ANGEL (Chairman)
Vela Gallego, Sonia (Secretary)
Martínez del Campo, Teresa (Member)
New Precision Antibiotics Based on the Inhibition of Shikimate Kinase Enzyme
Authorship
B.E.P.V.
Master in Organic Chemistry (3ª ed)
B.E.P.V.
Master in Organic Chemistry (3ª ed)
Defense date
09.13.2024 09:00
09.13.2024 09:00
Summary
The ability of antibiotics to effectively treat bacterial diseases is increasingly compromised due to the widespread use of broad-spectrum drugs and the rise of bacterial resistance. Consequently, strains of bacteria that are resistant to multiple drugs (superbugs) have emerged, making conventional treatments ineffective. Worldwide, bacterial resistance presents significant public health and economic challenges. Despite the urgency, pharmaceutical research into new antibiotics has decreased over the years. Precision antibiotics, which have targeted and specific actions, are emerging as a way to address infections without harming microbiomes or encouraging resistance. Identifying new classes of compounds that show no cross-resistance with existing antibiotics and operate via new mechanisms is proving to be a successful strategy. This master's thesis focuses on the shikimate kinase (SK, aroK gene) enzyme, the fifth enzyme in the shikimic acid pathway.Using a less common 'motion-based design approach,' we have explored the inhibition of the SK enzyme by ligands that can block the closure of the active site by reducing the flexibility of the LID and SB domains. In this master's project, the potential of hydroxylamines will be studied
The ability of antibiotics to effectively treat bacterial diseases is increasingly compromised due to the widespread use of broad-spectrum drugs and the rise of bacterial resistance. Consequently, strains of bacteria that are resistant to multiple drugs (superbugs) have emerged, making conventional treatments ineffective. Worldwide, bacterial resistance presents significant public health and economic challenges. Despite the urgency, pharmaceutical research into new antibiotics has decreased over the years. Precision antibiotics, which have targeted and specific actions, are emerging as a way to address infections without harming microbiomes or encouraging resistance. Identifying new classes of compounds that show no cross-resistance with existing antibiotics and operate via new mechanisms is proving to be a successful strategy. This master's thesis focuses on the shikimate kinase (SK, aroK gene) enzyme, the fifth enzyme in the shikimic acid pathway.Using a less common 'motion-based design approach,' we have explored the inhibition of the SK enzyme by ligands that can block the closure of the active site by reducing the flexibility of the LID and SB domains. In this master's project, the potential of hydroxylamines will be studied
Direction
GONZALEZ BELLO, CONCEPCION (Tutorships)
GONZALEZ BELLO, CONCEPCION (Tutorships)
Court
VARELA CARRETE, JESUS ANGEL (Chairman)
Vela Gallego, Sonia (Secretary)
Filippone , Salvatore (Member)
VARELA CARRETE, JESUS ANGEL (Chairman)
Vela Gallego, Sonia (Secretary)
Filippone , Salvatore (Member)
Photocatalytic hydroalkylation of trifluoromethyl alkenes with propane
Authorship
H.J.C.
Master in Organic Chemistry (3ª ed)
H.J.C.
Master in Organic Chemistry (3ª ed)
Defense date
07.18.2024 09:00
07.18.2024 09:00
Summary
Gaseous alkanes are widely available and affordable feedstocks with a highly underestimated potential as alkylating reagents. Photocatalytic processes based on hydrogen atom transfer (HAT) offer a sustainable approach to harness this potential. Using gaseous alkanes for synthesizing trifluoromethyl alkanes is particularly challenging, yet crucial, for drug discovery due to the beneficial properties of these fluorinated molecules. This Master’s thesis presents the development of a catalytic methodology for the direct hydroalkylation of trifluoroalkenes with propane based on HAT photocatalysis. The reaction affords trifluoromethyl alkanes with high selectivity and efficiency. Systematic screening of catalysts (FeCl3·6H2O and TBADT) and reaction conditions, according to the reduction potentials of the species involved, allowed making the reaction general and broadly applicable to the hydroalkylation of a range of substrates.
Gaseous alkanes are widely available and affordable feedstocks with a highly underestimated potential as alkylating reagents. Photocatalytic processes based on hydrogen atom transfer (HAT) offer a sustainable approach to harness this potential. Using gaseous alkanes for synthesizing trifluoromethyl alkanes is particularly challenging, yet crucial, for drug discovery due to the beneficial properties of these fluorinated molecules. This Master’s thesis presents the development of a catalytic methodology for the direct hydroalkylation of trifluoroalkenes with propane based on HAT photocatalysis. The reaction affords trifluoromethyl alkanes with high selectivity and efficiency. Systematic screening of catalysts (FeCl3·6H2O and TBADT) and reaction conditions, according to the reduction potentials of the species involved, allowed making the reaction general and broadly applicable to the hydroalkylation of a range of substrates.
Direction
FAÑANAS MASTRAL, MARTIN (Tutorships)
FAÑANAS MASTRAL, MARTIN (Tutorships)
Court
VARELA CARRETE, JESUS ANGEL (Chairman)
Vela Gallego, Sonia (Secretary)
Martínez del Campo, Teresa (Member)
VARELA CARRETE, JESUS ANGEL (Chairman)
Vela Gallego, Sonia (Secretary)
Martínez del Campo, Teresa (Member)
Determination of benzodiazepines in blood by GC-MS
Authorship
S.N.V.
Master's Degree in Chemical Research and Industrial Chemistry
S.N.V.
Master's Degree in Chemical Research and Industrial Chemistry
Defense date
07.18.2024 09:00
07.18.2024 09:00
Summary
Benzodiazepines are a class of central nervous system depressant medications, used for the treatment of anxiety and as muscle relaxants. Benzodiazepines are currently widely consumed in the global population and numerous cases of addiction and intoxication by these substances have appeared. In order to identify and quantify the presence of 7 benzodiazepines in the blood (diazepam, nordiazepam, midazolam, oxazepam, flurazepam, temazepam and lorazepam), a simple, fast and efficient extraction method has been adapted and validated, based on liquid-liquid extraction using ammonium buffer and chlorobutane as organic solvent. Subsequently, gas chromatography coupled with mass spectrometry was used for the detection and quantification of the analytes under study. This technique will allow us to separate all the analytes present in the sample and identify each one by its most representative ions. The developed method has been validated according to the requirements of the Food and Drug Administration (FDA) achieving a high sensitivity with limits of detection (LOD) and quantification (LOQ) of 2 ng/mL and 5 ng/mL respectively. Finally, the method was applied to 21 real samples received at the Forensic Toxicology Service of the USC.
Benzodiazepines are a class of central nervous system depressant medications, used for the treatment of anxiety and as muscle relaxants. Benzodiazepines are currently widely consumed in the global population and numerous cases of addiction and intoxication by these substances have appeared. In order to identify and quantify the presence of 7 benzodiazepines in the blood (diazepam, nordiazepam, midazolam, oxazepam, flurazepam, temazepam and lorazepam), a simple, fast and efficient extraction method has been adapted and validated, based on liquid-liquid extraction using ammonium buffer and chlorobutane as organic solvent. Subsequently, gas chromatography coupled with mass spectrometry was used for the detection and quantification of the analytes under study. This technique will allow us to separate all the analytes present in the sample and identify each one by its most representative ions. The developed method has been validated according to the requirements of the Food and Drug Administration (FDA) achieving a high sensitivity with limits of detection (LOD) and quantification (LOQ) of 2 ng/mL and 5 ng/mL respectively. Finally, the method was applied to 21 real samples received at the Forensic Toxicology Service of the USC.
Direction
BERMEJO BARRERA, ANA MARIA (Tutorships)
CABARCOS FERNANDEZ, PAMELA (Co-tutorships)
BERMEJO BARRERA, ANA MARIA (Tutorships)
CABARCOS FERNANDEZ, PAMELA (Co-tutorships)
Court
Sanmartin Matalobos, Jesus (Coordinator)
YEBRA BIURRUN, MARIA DEL CARMEN (Chairman)
Prieto Jiménez, Inmaculada (Secretary)
Carlosena Zubieta, Alatzne (Member)
Sanmartin Matalobos, Jesus (Coordinator)
YEBRA BIURRUN, MARIA DEL CARMEN (Chairman)
Prieto Jiménez, Inmaculada (Secretary)
Carlosena Zubieta, Alatzne (Member)
Synthesis and Characterization of a Porous Molecular Material Based on Tetraphenylmethane
Authorship
C.C.G.
Master in Organic Chemistry (3ª ed)
C.C.G.
Master in Organic Chemistry (3ª ed)
Defense date
09.13.2024 09:00
09.13.2024 09:00
Summary
The aim of this work was to synthesize and characterize a porous molecular material based on tetraphenylmethane, which contains a three-dimensional network of carbon-carbon bonds. Optimization and scaling of the synthetic route was carried out to obtain enough material to allow its characterization and detailed study of porosity. The synthesis, whose key stage consists of an alkene metathesis reaction, was carried out through a series of five reactions starting from trityl chloride (three from tetraphenylmethane), adjusting the conditions to improve the yield and purity of the product at each stage. The final material was characterized by IR and Raman spectroscopy, and a porosity analysis based on the adsorption of N2 and CO2 was performed. The results indicated that the material presents a high proportion of ultramicropores, which could be indicative of a crystalline structure with well-defined pores, a relevant characteristic for applications in gas storage and other fields.
The aim of this work was to synthesize and characterize a porous molecular material based on tetraphenylmethane, which contains a three-dimensional network of carbon-carbon bonds. Optimization and scaling of the synthetic route was carried out to obtain enough material to allow its characterization and detailed study of porosity. The synthesis, whose key stage consists of an alkene metathesis reaction, was carried out through a series of five reactions starting from trityl chloride (three from tetraphenylmethane), adjusting the conditions to improve the yield and purity of the product at each stage. The final material was characterized by IR and Raman spectroscopy, and a porosity analysis based on the adsorption of N2 and CO2 was performed. The results indicated that the material presents a high proportion of ultramicropores, which could be indicative of a crystalline structure with well-defined pores, a relevant characteristic for applications in gas storage and other fields.
Direction
TORNEIRO ABUIN, MERCEDES (Tutorships)
LAZZARI , MASSIMO (Co-tutorships)
TORNEIRO ABUIN, MERCEDES (Tutorships)
LAZZARI , MASSIMO (Co-tutorships)
Court
VARELA CARRETE, JESUS ANGEL (Chairman)
Vela Gallego, Sonia (Secretary)
Filippone , Salvatore (Member)
VARELA CARRETE, JESUS ANGEL (Chairman)
Vela Gallego, Sonia (Secretary)
Filippone , Salvatore (Member)
Towards antibacterial hydrogels. Synthesis, structural studies and biological activity
Authorship
M.C.D.D.
Master in Chemistry at the Interface of Biology and Materials Science
M.C.D.D.
Master in Chemistry at the Interface of Biology and Materials Science
Defense date
02.12.2023 10:00
02.12.2023 10:00
Summary
The controlled release of bioactive molecules and the encapsulation of living cells are active areas of research in drug discovery. Hydrogels are attracting significant attention in the medical field, particularly in drug delivery applications, due to their unique physical and chemical properties. This study focuses on the design and study of three new low molecular weight gelators (LMWGs) derived from N-alkylamides derived from beta-cyclohexanic amino acids. The study of their gel-forming properties was carried out by determining their minimum gelation concentration (mgc) in 14 solvents through a heating-cooling inversion test. Due to their potential applicability as drug delivery systems, the possibility of forming hydrogels was investigated, and it was only possible with two of the three gel-forming agents: Gt12-COOH and Gt12-NHNH2. These two hydrogels underwent structural studies using Infrared, X-ray and Scanning Electron Microscopy (SEM) to further understand their supramolecular organization and three-dimensional structures. Additionally, they were subjected to studies on the release of a model antibiotic, Ampicillin. These studies determined that the Gt12-COOH hydrogel formed with D-gluconolactone established temporal control in drug release, prolonging its activity over time and positioning itself as a promising candidate for drug delivery applications. To conclude, the activity of both hydrogels was studied in biological cultures. A surprising inhibitory effect in the negative control of Gt12-COOH-GdL led to the consideration of various hypotheses regarding its interaction with different bacterial strains in the study. This antibacterial activity was ultimately linked to a tendency towards filamentation, observed exclusively in Gram-negative microorganisms.
The controlled release of bioactive molecules and the encapsulation of living cells are active areas of research in drug discovery. Hydrogels are attracting significant attention in the medical field, particularly in drug delivery applications, due to their unique physical and chemical properties. This study focuses on the design and study of three new low molecular weight gelators (LMWGs) derived from N-alkylamides derived from beta-cyclohexanic amino acids. The study of their gel-forming properties was carried out by determining their minimum gelation concentration (mgc) in 14 solvents through a heating-cooling inversion test. Due to their potential applicability as drug delivery systems, the possibility of forming hydrogels was investigated, and it was only possible with two of the three gel-forming agents: Gt12-COOH and Gt12-NHNH2. These two hydrogels underwent structural studies using Infrared, X-ray and Scanning Electron Microscopy (SEM) to further understand their supramolecular organization and three-dimensional structures. Additionally, they were subjected to studies on the release of a model antibiotic, Ampicillin. These studies determined that the Gt12-COOH hydrogel formed with D-gluconolactone established temporal control in drug release, prolonging its activity over time and positioning itself as a promising candidate for drug delivery applications. To conclude, the activity of both hydrogels was studied in biological cultures. A surprising inhibitory effect in the negative control of Gt12-COOH-GdL led to the consideration of various hypotheses regarding its interaction with different bacterial strains in the study. This antibacterial activity was ultimately linked to a tendency towards filamentation, observed exclusively in Gram-negative microorganisms.
Direction
ESTEVEZ CABANAS, JUAN CARLOS (Tutorships)
ESTEVEZ CABANAS, JUAN CARLOS (Tutorships)
Court
RIVADULLA FERNANDEZ, JOSE FRANCISCO (Chairman)
NAPPI , MANUEL (Secretary)
PELAZ GARCIA, BEATRIZ (Member)
RIVADULLA FERNANDEZ, JOSE FRANCISCO (Chairman)
NAPPI , MANUEL (Secretary)
PELAZ GARCIA, BEATRIZ (Member)
Study of National Population Exposure to Plastic-Related Chemical Compounds through Wastewater Analysis for Epidemiological Purposes.
Authorship
H.M.G.L.
Master's Degree in Chemical Research and Industrial Chemistry
H.M.G.L.
Master's Degree in Chemical Research and Industrial Chemistry
Defense date
09.16.2024 09:00
09.16.2024 09:00
Summary
Plasticizers are chemical compounds used as additives or property modulators in the production of plastics for a wide range of applications. These compounds are found in numerous everyday products, from food packaging to electrical cables and supermarket bags, resulting in involuntary human exposure through various routes such as ingestion or inhalation. Given the potential of some of these plasticizers to disrupt the endocrine system and the unknown toxicity of others, it is crucial to develop effective methods for their monitoring and evaluation. This master’s Thesis (TFM) focused on the application of WBE (wastewater-based epidemiology) methodology. WBE is an analytical methodology that uses wastewater collected at wastewater treatment plants (WWTPs) as a biological sample of diluted urine from a population, allowing the estimation of human exposure to various chemical agents, specifically plasticizers, by monitoring various biomarkers present in the water resulting from human metabolism. Using the WBE methodology, plasticizer concentrations were estimated in different regions of two autonomous communities in Spain. Furthermore, the daily excretion load of metabolites per person was calculated, which allowed the determination of human exposure to these plasticizers in a population group, with elevated values observed for some of the studied metabolites. Finally, plasticizer levels were compared with the established Tolerable Daily Intake (TDI) values, providing a detailed insight into population exposure to these chemical compounds and assessing whether this exposure constitutes a significant health risk.
Plasticizers are chemical compounds used as additives or property modulators in the production of plastics for a wide range of applications. These compounds are found in numerous everyday products, from food packaging to electrical cables and supermarket bags, resulting in involuntary human exposure through various routes such as ingestion or inhalation. Given the potential of some of these plasticizers to disrupt the endocrine system and the unknown toxicity of others, it is crucial to develop effective methods for their monitoring and evaluation. This master’s Thesis (TFM) focused on the application of WBE (wastewater-based epidemiology) methodology. WBE is an analytical methodology that uses wastewater collected at wastewater treatment plants (WWTPs) as a biological sample of diluted urine from a population, allowing the estimation of human exposure to various chemical agents, specifically plasticizers, by monitoring various biomarkers present in the water resulting from human metabolism. Using the WBE methodology, plasticizer concentrations were estimated in different regions of two autonomous communities in Spain. Furthermore, the daily excretion load of metabolites per person was calculated, which allowed the determination of human exposure to these plasticizers in a population group, with elevated values observed for some of the studied metabolites. Finally, plasticizer levels were compared with the established Tolerable Daily Intake (TDI) values, providing a detailed insight into population exposure to these chemical compounds and assessing whether this exposure constitutes a significant health risk.
Direction
QUINTANA ALVAREZ, JOSE BENITO (Tutorships)
RODIL RODRIGUEZ, MARIA DEL ROSARIO (Co-tutorships)
QUINTANA ALVAREZ, JOSE BENITO (Tutorships)
RODIL RODRIGUEZ, MARIA DEL ROSARIO (Co-tutorships)
Court
Sanmartin Matalobos, Jesus (Coordinator)
FIOL LOPEZ, SARAH (Chairman)
MOSQUERA MOSQUERA, JESUS (Secretary)
Rosales Villanueva, Emilio (Member)
Sanmartin Matalobos, Jesus (Coordinator)
FIOL LOPEZ, SARAH (Chairman)
MOSQUERA MOSQUERA, JESUS (Secretary)
Rosales Villanueva, Emilio (Member)
Influence of the spacer on the formation of complexes with bishydrazone ligands
Authorship
A.M.B.C.
Master's Degree in Chemical Research and Industrial Chemistry
A.M.B.C.
Master's Degree in Chemical Research and Industrial Chemistry
Defense date
07.18.2024 09:00
07.18.2024 09:00
Summary
The present Master´s Dissertation has focused on the design and synthesis of two bishydrazone ligands that are potentially precursors of helicate-type systems: H2L1, a tetradentate [N2O2] ligand without a donor atom in the spacer; and H2L2, a pentadentate [N3O2] ligand that features an nitrogen donor atom in the spacer. Once isolated and characterised, the coordination chemistry of the ligands was studied with zinc (II), copper (II), nickel (II), cobalt (II), iron (II) and manganese (II) metal ions using an electrochemical methodology. The Fe(II), Co(II), Ni(II), Cu(II), and Zn(II) complexes are dinuclear species with a helicate-type structure, while the only isolated Mn(II) complex is a monomer with a pentagonal pyramidal structure.
The present Master´s Dissertation has focused on the design and synthesis of two bishydrazone ligands that are potentially precursors of helicate-type systems: H2L1, a tetradentate [N2O2] ligand without a donor atom in the spacer; and H2L2, a pentadentate [N3O2] ligand that features an nitrogen donor atom in the spacer. Once isolated and characterised, the coordination chemistry of the ligands was studied with zinc (II), copper (II), nickel (II), cobalt (II), iron (II) and manganese (II) metal ions using an electrochemical methodology. The Fe(II), Co(II), Ni(II), Cu(II), and Zn(II) complexes are dinuclear species with a helicate-type structure, while the only isolated Mn(II) complex is a monomer with a pentagonal pyramidal structure.
Direction
PEDRIDO CASTIÑEIRAS, ROSA MARIA (Tutorships)
MARTINEZ CALVO, MIGUEL (Co-tutorships)
PEDRIDO CASTIÑEIRAS, ROSA MARIA (Tutorships)
MARTINEZ CALVO, MIGUEL (Co-tutorships)
Court
Sanmartin Matalobos, Jesus (Coordinator)
Valencia Matarranz, Laura Mª (Chairman)
FERNANDEZ TRILLO, FRANCISCO (Secretary)
GONZALEZ NOYA, ANA MARIA (Member)
Sanmartin Matalobos, Jesus (Coordinator)
Valencia Matarranz, Laura Mª (Chairman)
FERNANDEZ TRILLO, FRANCISCO (Secretary)
GONZALEZ NOYA, ANA MARIA (Member)
First studies about the photodegradation of emerging contaminants from tire rubber
Authorship
V.C.F.
Master's Degree in Chemical Research and Industrial Chemistry
V.C.F.
Master's Degree in Chemical Research and Industrial Chemistry
Defense date
07.18.2024 09:00
07.18.2024 09:00
Summary
Concern about the use of microplastics derived from tire recycling in facilities such as sports fields and other leisure spaces is a scientific topic of great interest today. Tire rubber contains numerous chemical substances added to improve its properties that, due to wear, are introduced into the environment, generating a serious threat. Among these compounds are the antiozonant 6PPD (N(1,3dimethylbutyl)Nphenyl p phenylenediamine) and its derivative product 6PPDquinone, recently linked to the death of aquatic species. The main objective of this work is to investigate the photochemical behavior of antioxidants, vulcanizers and other contaminants present in tire rubber, including 6PPD and 6PPDq. To extract the compounds from water, the solid phase microextraction (SPME) technique is used. The determination and quantification is carried out using gas chromatography coupled to tandem mass spectrometry (GC MSMS), which allows subsequent reliable analysis of real samples. The photodegradation of the compounds is studied both in water and on a solid support using the extraction fiber (photo-SPME). The kinetic results show that the photodegradation process occurs in both media, but at different rates depending on the analyte. This demonstrates that photodegradation can occur naturally in the environment, and is shown to be an effective process for the purification of contaminated water. This study is novel due to the small number of studies that exist with this topic. No studies have been found for DMDA, DMTDA, DPPD, IPPD and MBTZ.
Concern about the use of microplastics derived from tire recycling in facilities such as sports fields and other leisure spaces is a scientific topic of great interest today. Tire rubber contains numerous chemical substances added to improve its properties that, due to wear, are introduced into the environment, generating a serious threat. Among these compounds are the antiozonant 6PPD (N(1,3dimethylbutyl)Nphenyl p phenylenediamine) and its derivative product 6PPDquinone, recently linked to the death of aquatic species. The main objective of this work is to investigate the photochemical behavior of antioxidants, vulcanizers and other contaminants present in tire rubber, including 6PPD and 6PPDq. To extract the compounds from water, the solid phase microextraction (SPME) technique is used. The determination and quantification is carried out using gas chromatography coupled to tandem mass spectrometry (GC MSMS), which allows subsequent reliable analysis of real samples. The photodegradation of the compounds is studied both in water and on a solid support using the extraction fiber (photo-SPME). The kinetic results show that the photodegradation process occurs in both media, but at different rates depending on the analyte. This demonstrates that photodegradation can occur naturally in the environment, and is shown to be an effective process for the purification of contaminated water. This study is novel due to the small number of studies that exist with this topic. No studies have been found for DMDA, DMTDA, DPPD, IPPD and MBTZ.
Direction
LLOMPART VIZOSO, MARIA PILAR (Tutorships)
LLOMPART VIZOSO, MARIA PILAR (Tutorships)
Court
Sanmartin Matalobos, Jesus (Coordinator)
YEBRA BIURRUN, MARIA DEL CARMEN (Chairman)
Prieto Jiménez, Inmaculada (Secretary)
Carlosena Zubieta, Alatzne (Member)
Sanmartin Matalobos, Jesus (Coordinator)
YEBRA BIURRUN, MARIA DEL CARMEN (Chairman)
Prieto Jiménez, Inmaculada (Secretary)
Carlosena Zubieta, Alatzne (Member)
Octahydroisoindoles derived from (-)-shikimic acid, glucosidase inhibitors
Authorship
S.G.U.
Master in Organic Chemistry (3ª ed)
S.G.U.
Master in Organic Chemistry (3ª ed)
Defense date
07.18.2024 09:00
07.18.2024 09:00
Summary
Iminosugars represent a class of monosaccharides where the endocyclic oxygen atom is replaced by a nitrogen atom. This alteration gives them the ability to interfere with the action of natural glycosidases, which makes them relevant elements in the metabolism of glycoproteins, glycogen and the control of some genetic diseases, such as lysosomal accumulation diseases. In addition to iminosugars, numerous polyhydroxylated molecules containing amino groups in their structure exhibit similar properties, which underlines the importance of synthesizing and studying these substances as new compounds with biological activity, useful in the field of Medicinal Chemistry. Polyhydroxylated isoindoles are notable for their properties and are consequently considered potential inhibitors of glycosidases. This Master's Thesis focuses on the synthesis of new polyhydroxylated isoindoles using (-)-shikimic acid as a starting product, a natural compound currently commercially available at affordable prices.
Iminosugars represent a class of monosaccharides where the endocyclic oxygen atom is replaced by a nitrogen atom. This alteration gives them the ability to interfere with the action of natural glycosidases, which makes them relevant elements in the metabolism of glycoproteins, glycogen and the control of some genetic diseases, such as lysosomal accumulation diseases. In addition to iminosugars, numerous polyhydroxylated molecules containing amino groups in their structure exhibit similar properties, which underlines the importance of synthesizing and studying these substances as new compounds with biological activity, useful in the field of Medicinal Chemistry. Polyhydroxylated isoindoles are notable for their properties and are consequently considered potential inhibitors of glycosidases. This Master's Thesis focuses on the synthesis of new polyhydroxylated isoindoles using (-)-shikimic acid as a starting product, a natural compound currently commercially available at affordable prices.
Direction
ESTEVEZ CABANAS, JUAN CARLOS (Tutorships)
ESTEVEZ CABANAS, RAMON JOSE (Co-tutorships)
ESTEVEZ CABANAS, JUAN CARLOS (Tutorships)
ESTEVEZ CABANAS, RAMON JOSE (Co-tutorships)
Court
VARELA CARRETE, JESUS ANGEL (Chairman)
Vela Gallego, Sonia (Secretary)
Martínez del Campo, Teresa (Member)
VARELA CARRETE, JESUS ANGEL (Chairman)
Vela Gallego, Sonia (Secretary)
Martínez del Campo, Teresa (Member)
Synthesis of Dendrímers by Thermal Azide - Alkyne Cicloadition with internal Alkynes
Authorship
H.E.F.P.
Master in Organic Chemistry (3ª ed)
H.E.F.P.
Master in Organic Chemistry (3ª ed)
Defense date
07.18.2024 09:00
07.18.2024 09:00
Summary
Dendrimers are tree like molecules that have gained significant interest in various research areas because of a characteristic known as Multivalency, which makes them have more and more applications and, therefore, it is necessary to develop fast and efficient synthesis methods. In this study, we aim to synthesize a new dendrimer using a divergent pathway starting with common reagents and short, efficient, and green synthesis pathways, using atom economic and metal free reactions. Our plan relies on leveraging the potential of AAC to obtain clean reaction products quickly, in gram scale and under mild conditions. Additionally, we will attempt to investigate through NMR experiments the origin of aggregate formation during dendrimer synthesis, a common issue across all dendrimer families.
Dendrimers are tree like molecules that have gained significant interest in various research areas because of a characteristic known as Multivalency, which makes them have more and more applications and, therefore, it is necessary to develop fast and efficient synthesis methods. In this study, we aim to synthesize a new dendrimer using a divergent pathway starting with common reagents and short, efficient, and green synthesis pathways, using atom economic and metal free reactions. Our plan relies on leveraging the potential of AAC to obtain clean reaction products quickly, in gram scale and under mild conditions. Additionally, we will attempt to investigate through NMR experiments the origin of aggregate formation during dendrimer synthesis, a common issue across all dendrimer families.
Direction
FERNANDEZ MEGIA, EDUARDO (Tutorships)
FERNANDEZ MEGIA, EDUARDO (Tutorships)
Court
VARELA CARRETE, JESUS ANGEL (Chairman)
Vela Gallego, Sonia (Secretary)
Martínez del Campo, Teresa (Member)
VARELA CARRETE, JESUS ANGEL (Chairman)
Vela Gallego, Sonia (Secretary)
Martínez del Campo, Teresa (Member)
Straightforward synthesis of spirolactones via photocatalytic CO2 fixation
Authorship
M.R.M.
Master in Organic Chemistry (3ª ed)
M.R.M.
Master in Organic Chemistry (3ª ed)
Defense date
07.18.2024 09:00
07.18.2024 09:00
Summary
Spirocyclic lactones are prevalent structural motifs in bioactive molecules, owing to the presence of the spirocenter which directly impacts their biodynamic properties. Due to the importance of these structures, different methodologies have been developed for their synthesis, requiring previously functionalized starting materials, metal catalysts, or even the use of highly toxic compounds. In this context, it is of great interest to develop new, gentler and environmentally friendly strategies. Within the framework of this line of research, a new photocatalytic method is proposed that allows the formation of gamma-spirolactones from simple cyclic ketones and carbon dioxide, without the use of toxic and expensive metal complexes. In this project we will proceed to finalize the optimization and study the scope of this methodology, observing the formation of gamma-spirolactones through a wide variety of substrates.
Spirocyclic lactones are prevalent structural motifs in bioactive molecules, owing to the presence of the spirocenter which directly impacts their biodynamic properties. Due to the importance of these structures, different methodologies have been developed for their synthesis, requiring previously functionalized starting materials, metal catalysts, or even the use of highly toxic compounds. In this context, it is of great interest to develop new, gentler and environmentally friendly strategies. Within the framework of this line of research, a new photocatalytic method is proposed that allows the formation of gamma-spirolactones from simple cyclic ketones and carbon dioxide, without the use of toxic and expensive metal complexes. In this project we will proceed to finalize the optimization and study the scope of this methodology, observing the formation of gamma-spirolactones through a wide variety of substrates.
Direction
SAA RODRIGUEZ, CARLOS EUGENIO (Tutorships)
NAPPI , MANUEL (Co-tutorships)
SAA RODRIGUEZ, CARLOS EUGENIO (Tutorships)
NAPPI , MANUEL (Co-tutorships)
Court
VARELA CARRETE, JESUS ANGEL (Chairman)
Vela Gallego, Sonia (Secretary)
Martínez del Campo, Teresa (Member)
VARELA CARRETE, JESUS ANGEL (Chairman)
Vela Gallego, Sonia (Secretary)
Martínez del Campo, Teresa (Member)
Metal complexes derived from bid8nido-imine-carboranes)
Authorship
B.L.L.
Master's Degree in Chemical Research and Industrial Chemistry
B.L.L.
Master's Degree in Chemical Research and Industrial Chemistry
Defense date
07.18.2024 09:00
07.18.2024 09:00
Summary
The development of metallodrugs derived from carborane is a recent field with promising medical applications, due to the peculiarities that this cluster presents. As a contribution, the synthesis of different ligands derived from nido-carborane was designed, all of them functionalized with a Schiff base (C=N) on one of the carbons of the carborane cluster. The presence of these potentially donor groups (N) combined with the properties of nido-carborane, will help the coordination of metal centers. The imine ligand nido-B1 is monodentate and was obtained by deboronation of the closo derivative, obtained in turn by the aza-Wittig reaction. Its coordinative capacity was studied with ruthenium precursors. The imine ligand nido-B2 was obtained in an analogous way. It presents two units similar to the nido-B1 imine connected by an aromatic spacer, so it is bidentate (N, N). Its coordinative capacity was studied with ruthenium and palladium precursors. The nido-B3 and B4 imine ligands are analogous to B2 but with an aliphatic linker. This variant did not allow the closo derivatives to be obtained by the aza-Wittig reaction, so they could not be obtained.
The development of metallodrugs derived from carborane is a recent field with promising medical applications, due to the peculiarities that this cluster presents. As a contribution, the synthesis of different ligands derived from nido-carborane was designed, all of them functionalized with a Schiff base (C=N) on one of the carbons of the carborane cluster. The presence of these potentially donor groups (N) combined with the properties of nido-carborane, will help the coordination of metal centers. The imine ligand nido-B1 is monodentate and was obtained by deboronation of the closo derivative, obtained in turn by the aza-Wittig reaction. Its coordinative capacity was studied with ruthenium precursors. The imine ligand nido-B2 was obtained in an analogous way. It presents two units similar to the nido-B1 imine connected by an aromatic spacer, so it is bidentate (N, N). Its coordinative capacity was studied with ruthenium and palladium precursors. The nido-B3 and B4 imine ligands are analogous to B2 but with an aliphatic linker. This variant did not allow the closo derivatives to be obtained by the aza-Wittig reaction, so they could not be obtained.
Direction
SOUSA PEDRARES, ANTONIO (Tutorships)
SOUSA PEDRARES, ANTONIO (Tutorships)
Court
Sanmartin Matalobos, Jesus (Coordinator)
Valencia Matarranz, Laura Mª (Chairman)
FERNANDEZ TRILLO, FRANCISCO (Secretary)
GONZALEZ NOYA, ANA MARIA (Member)
Sanmartin Matalobos, Jesus (Coordinator)
Valencia Matarranz, Laura Mª (Chairman)
FERNANDEZ TRILLO, FRANCISCO (Secretary)
GONZALEZ NOYA, ANA MARIA (Member)
Design and synthesis of cyclometallated compounds with tridentate [C,N,S] and [C,N,O] ligands
Authorship
X.H.V.
Master's Degree in Chemical Research and Industrial Chemistry
X.H.V.
Master's Degree in Chemical Research and Industrial Chemistry
Defense date
07.18.2024 09:00
07.18.2024 09:00
Summary
In this work a study was fulfilled related to different modes of coordination between carbon and palladium or platinum when synthesizing cyclometallated compounds from tridentate ligands [C,N,S] and [C,N,O] derived from thiosemicarbazones and Schiff bases. These ligands were obtained by the condensation reaction between thiosemicarbazides or aniline derivatives with benzaldehydes and are reacted with different palladium salts and a platinum salt. When thiosemicarbazones, acting as tridented ligands [C,N,S], react with potassium tetrachloropalate complexes are obtained where the metal is forming a 5 members ring and metalation involves a sp2 carbon, while when palladium acetate is used, it is observed that in the product palladium forms a 6 members ring and is linked to a sp3 carbon. In the case of Schiff bases, it was not possible to obtain the expected products for the ligand [C,N,S], whereas for the ligand [C,N,O] the obtaining of the cyclometallated complex by the sp2 carbon is checked by using palladium acetate. Finally, platinum derivatives are synthesized using triphenylphosphine and a short-chain diphosphine, the latter with the aim of forming an intermetallic bridge to link palladacycles to give heterodinuclear compounds. The results obtained for the latter complexes showed the presence of a mixture of species that did not allow for correct characterization.
In this work a study was fulfilled related to different modes of coordination between carbon and palladium or platinum when synthesizing cyclometallated compounds from tridentate ligands [C,N,S] and [C,N,O] derived from thiosemicarbazones and Schiff bases. These ligands were obtained by the condensation reaction between thiosemicarbazides or aniline derivatives with benzaldehydes and are reacted with different palladium salts and a platinum salt. When thiosemicarbazones, acting as tridented ligands [C,N,S], react with potassium tetrachloropalate complexes are obtained where the metal is forming a 5 members ring and metalation involves a sp2 carbon, while when palladium acetate is used, it is observed that in the product palladium forms a 6 members ring and is linked to a sp3 carbon. In the case of Schiff bases, it was not possible to obtain the expected products for the ligand [C,N,S], whereas for the ligand [C,N,O] the obtaining of the cyclometallated complex by the sp2 carbon is checked by using palladium acetate. Finally, platinum derivatives are synthesized using triphenylphosphine and a short-chain diphosphine, the latter with the aim of forming an intermetallic bridge to link palladacycles to give heterodinuclear compounds. The results obtained for the latter complexes showed the presence of a mixture of species that did not allow for correct characterization.
Direction
DURAN CARRIL, MARIA LUZ (Tutorships)
VILA ABAD, JOSE MANUEL (Co-tutorships)
DURAN CARRIL, MARIA LUZ (Tutorships)
VILA ABAD, JOSE MANUEL (Co-tutorships)
Court
Sanmartin Matalobos, Jesus (Coordinator)
Valencia Matarranz, Laura Mª (Chairman)
FERNANDEZ TRILLO, FRANCISCO (Secretary)
GONZALEZ NOYA, ANA MARIA (Member)
Sanmartin Matalobos, Jesus (Coordinator)
Valencia Matarranz, Laura Mª (Chairman)
FERNANDEZ TRILLO, FRANCISCO (Secretary)
GONZALEZ NOYA, ANA MARIA (Member)
Development of electrochemical methods for the synthesis of functional PAHs
Authorship
C.L.V.
Master in Organic Chemistry (3ª ed)
C.L.V.
Master in Organic Chemistry (3ª ed)
Defense date
07.18.2024 09:00
07.18.2024 09:00
Summary
Polycyclic aromatic hydrocarbons (PAHs) occupy a prominent position in the field of organic molecular materials due to the interesting electronic, optical and self-assembly properties presented by some of these compounds. The bottom-up approaches for the synthesis of PAHs usually require the previous construction of non-planar precursors, soluble in common organic solvents, preceding a final step that often involves either an oxidation or a reduction process. This final step may include a Scholl type cyclodehydrogenation, or a reductive aromatization reaction from an adequate precursor. Recently, electrochemical methods for the synthesis of PAHs through oxidative cyclodehydrogenation reactions have been developed, but there are no significant precedents of electrochemical reductions leading to polyarenes. The experience of our group in the synthesis of acenes and other PAHs by means of cycloaddition reactions of arynes with furans and isobenzofurans, led us to study the electrochemical deoxygenation of epoxyarenes. With this aim, a family of epoxyarenes with diverse structures have been synthetized, their reduction potentials were determined by cyclic voltammetry and/or square wave voltammetry and conditions for the deoxygenation under electrochemical reduction were investigated, obtaining the corresponding aromatic hydrocarbon or/and the formation of dihydro-derivative(s) depending on the structure of the polycyclic system.
Polycyclic aromatic hydrocarbons (PAHs) occupy a prominent position in the field of organic molecular materials due to the interesting electronic, optical and self-assembly properties presented by some of these compounds. The bottom-up approaches for the synthesis of PAHs usually require the previous construction of non-planar precursors, soluble in common organic solvents, preceding a final step that often involves either an oxidation or a reduction process. This final step may include a Scholl type cyclodehydrogenation, or a reductive aromatization reaction from an adequate precursor. Recently, electrochemical methods for the synthesis of PAHs through oxidative cyclodehydrogenation reactions have been developed, but there are no significant precedents of electrochemical reductions leading to polyarenes. The experience of our group in the synthesis of acenes and other PAHs by means of cycloaddition reactions of arynes with furans and isobenzofurans, led us to study the electrochemical deoxygenation of epoxyarenes. With this aim, a family of epoxyarenes with diverse structures have been synthetized, their reduction potentials were determined by cyclic voltammetry and/or square wave voltammetry and conditions for the deoxygenation under electrochemical reduction were investigated, obtaining the corresponding aromatic hydrocarbon or/and the formation of dihydro-derivative(s) depending on the structure of the polycyclic system.
Direction
PEREZ MEIRAS, MARIA DOLORES (Tutorships)
PEREZ MEIRAS, MARIA DOLORES (Tutorships)
Court
VARELA CARRETE, JESUS ANGEL (Chairman)
Vela Gallego, Sonia (Secretary)
Martínez del Campo, Teresa (Member)
VARELA CARRETE, JESUS ANGEL (Chairman)
Vela Gallego, Sonia (Secretary)
Martínez del Campo, Teresa (Member)
Evaluation of computerized tools for the development of liquid chromatography-mass spectrometry separations.
Authorship
E.G.D.P.
Master's Degree in Chemical Research and Industrial Chemistry
E.G.D.P.
Master's Degree in Chemical Research and Industrial Chemistry
Defense date
09.16.2024 09:00
09.16.2024 09:00
Summary
The present Master's Thesis (TFM) addresses the evaluation of computerized tools for developing separations by liquid chromatography coupled with mass spectrometry (LC-MS) using the Mchrom Scout program from Mestrelab Research S.L. With a particular focus on reverse-phase chromatography and target-type projects, where the primary goal is the separation of mixtures to isolate a specific component of interest. Various computerized tools for experimental design, retention modeling, and separation optimization are explored. The study analyzes the development of computer-aided method development (CAMD) to optimize chromatographic conditions, using different multi-objective optimization strategies (MOOP). Additionally, advanced techniques for evaluating peak purity will be used, including Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) and direct fragment ion assignment methods, to ensure the homogeneity and precision of chromatographic peaks.
The present Master's Thesis (TFM) addresses the evaluation of computerized tools for developing separations by liquid chromatography coupled with mass spectrometry (LC-MS) using the Mchrom Scout program from Mestrelab Research S.L. With a particular focus on reverse-phase chromatography and target-type projects, where the primary goal is the separation of mixtures to isolate a specific component of interest. Various computerized tools for experimental design, retention modeling, and separation optimization are explored. The study analyzes the development of computer-aided method development (CAMD) to optimize chromatographic conditions, using different multi-objective optimization strategies (MOOP). Additionally, advanced techniques for evaluating peak purity will be used, including Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) and direct fragment ion assignment methods, to ensure the homogeneity and precision of chromatographic peaks.
Direction
SARDINA LOPEZ, FRANCISCO JAVIER (Tutorships)
SARDINA LOPEZ, FRANCISCO JAVIER (Tutorships)
Court
Sanmartin Matalobos, Jesus (Coordinator)
FIOL LOPEZ, SARAH (Chairman)
MOSQUERA MOSQUERA, JESUS (Secretary)
Rosales Villanueva, Emilio (Member)
Sanmartin Matalobos, Jesus (Coordinator)
FIOL LOPEZ, SARAH (Chairman)
MOSQUERA MOSQUERA, JESUS (Secretary)
Rosales Villanueva, Emilio (Member)
Computational tools in cancer and infection studies: the cellular membrane as a therapeutic target
Authorship
P.R.L.
Master in Organic Chemistry (3ª ed)
P.R.L.
Master in Organic Chemistry (3ª ed)
Defense date
07.18.2024 09:00
07.18.2024 09:00
Summary
The rising number of antibiotic resistant pathogens is a global problem that has concerned the World Health Organization (WHO) and scientists alike for the last couple of decades. This threat has made evident the need of developing new drugs capable of fighting these pathogens without developing new resistance mechanisms. Antimicrobial peptides arise as a promising alternative thanks to their capability of being able to differentiate between bacteria and healthy cells by the different lipidic composition of their membranes. Among them, cyclic peptides, planar structures which alternate D- and L-amino acids and can self-assemble into nanotubes, the active species in favourable conditions such as in the presence of a pathogen; are specially enticing. Molecular dynamic (DM) simulations have been key to understanding the interactions between cyclopeptides (CPs), though coarse grain (CG) models such as MARTINI can´t model properly the hydrogen bonds between atoms. Trying to fix this problem, MARTINI 2.2 was extended with the MA(R/S)TINI parametrization, which includes the quirality of each residue, reproducing the expected self-assembling patterns without an increased computational cost. The goal of this work is to adapt this implementation to MARTINI 3, validating it with various peptide sequences in different lipidic membranes, manifesting that the interactions are sensitive to the chirality of peptide and the results compare favourably with previous results.
The rising number of antibiotic resistant pathogens is a global problem that has concerned the World Health Organization (WHO) and scientists alike for the last couple of decades. This threat has made evident the need of developing new drugs capable of fighting these pathogens without developing new resistance mechanisms. Antimicrobial peptides arise as a promising alternative thanks to their capability of being able to differentiate between bacteria and healthy cells by the different lipidic composition of their membranes. Among them, cyclic peptides, planar structures which alternate D- and L-amino acids and can self-assemble into nanotubes, the active species in favourable conditions such as in the presence of a pathogen; are specially enticing. Molecular dynamic (DM) simulations have been key to understanding the interactions between cyclopeptides (CPs), though coarse grain (CG) models such as MARTINI can´t model properly the hydrogen bonds between atoms. Trying to fix this problem, MARTINI 2.2 was extended with the MA(R/S)TINI parametrization, which includes the quirality of each residue, reproducing the expected self-assembling patterns without an increased computational cost. The goal of this work is to adapt this implementation to MARTINI 3, validating it with various peptide sequences in different lipidic membranes, manifesting that the interactions are sensitive to the chirality of peptide and the results compare favourably with previous results.
Direction
GARCIA FANDIÑO, REBECA (Tutorships)
GARCIA FANDIÑO, REBECA (Tutorships)
Court
VARELA CARRETE, JESUS ANGEL (Chairman)
Vela Gallego, Sonia (Secretary)
Martínez del Campo, Teresa (Member)
VARELA CARRETE, JESUS ANGEL (Chairman)
Vela Gallego, Sonia (Secretary)
Martínez del Campo, Teresa (Member)
Determination of fentanyl in plasma by gas chromatography coupled to mass spectrometry.
Authorship
R.F.V.
Master's Degree in Chemical Research and Industrial Chemistry
R.F.V.
Master's Degree in Chemical Research and Industrial Chemistry
Defense date
07.18.2024 09:00
07.18.2024 09:00
Summary
Fentanyl is an approved opioid drug for clinical use as an analgesic and anaesthetic. In recent years, the use of so-called illegal fentanyl has skyrocketed, especially in the United States and, consequently, an increasing number of poisonings, some of them lethal, are occurring. This is why efficient analytical methods are needed for its determination in biological samples. The objective of this master's thesis is to develop, optimize and validate an analytical method for the determination of the opioid fentanyl and the adulterant xylazine in plasma by gas chromatography coupled to mass spectrometry (GC-MS). Optimization is carried out first for the chromatographic conditions and then for the liquid-liquid extraction (LLE) technique selected from several procedures. The optimization of the extraction procedure aims to improve and develop a more sustainable method. The validation of the analytical method is carried out according to FDA (Food and Drug Administration) and ANSI/ASB (American National Standard Institute/Academy Standards Board) guidelines. Finally, the analytical method is applied for the determination of fentanyl in 11 postmortem samples of real cases received at the USC Institute of Forensic Sciences.
Fentanyl is an approved opioid drug for clinical use as an analgesic and anaesthetic. In recent years, the use of so-called illegal fentanyl has skyrocketed, especially in the United States and, consequently, an increasing number of poisonings, some of them lethal, are occurring. This is why efficient analytical methods are needed for its determination in biological samples. The objective of this master's thesis is to develop, optimize and validate an analytical method for the determination of the opioid fentanyl and the adulterant xylazine in plasma by gas chromatography coupled to mass spectrometry (GC-MS). Optimization is carried out first for the chromatographic conditions and then for the liquid-liquid extraction (LLE) technique selected from several procedures. The optimization of the extraction procedure aims to improve and develop a more sustainable method. The validation of the analytical method is carried out according to FDA (Food and Drug Administration) and ANSI/ASB (American National Standard Institute/Academy Standards Board) guidelines. Finally, the analytical method is applied for the determination of fentanyl in 11 postmortem samples of real cases received at the USC Institute of Forensic Sciences.
Direction
SÁNCHEZ SELLERO, INÉS (Tutorships)
Álvarez Freire, Iván (Co-tutorships)
SÁNCHEZ SELLERO, INÉS (Tutorships)
Álvarez Freire, Iván (Co-tutorships)
Court
Sanmartin Matalobos, Jesus (Coordinator)
YEBRA BIURRUN, MARIA DEL CARMEN (Chairman)
Prieto Jiménez, Inmaculada (Secretary)
Carlosena Zubieta, Alatzne (Member)
Sanmartin Matalobos, Jesus (Coordinator)
YEBRA BIURRUN, MARIA DEL CARMEN (Chairman)
Prieto Jiménez, Inmaculada (Secretary)
Carlosena Zubieta, Alatzne (Member)
Ru(II) catalysed [2+2+1] cycloadditions between alkynes and azides
Authorship
M.P.C.
Master in Organic Chemistry (3ª ed)
M.P.C.
Master in Organic Chemistry (3ª ed)
Defense date
07.18.2024 09:00
07.18.2024 09:00
Summary
Five-, six-, and seven-membered azaheterocycles are common nuclei in many drugs and pharmaceuticals. An attractive and sustainable strategy to their synthesis is based on metal-catalyzed cycloadditions of easily available partners. Thus, thermal and/or photoirradiated metal -(Co(I), Rh (I), Ru(II), Fe(II))- catalyzed [2+2+2] cycloadditions of alkynes and nitriles have been widely studied and successfully applied to the synthesis of pyridines. However, access to the pyrrole ring through metal-catalyzed [2+2+1] cycloadditions of readily available unsaturated partners has been more restricted. Having in mind the advantages of ruthenium over other transition metals and the availability of azides as nitrene precursors, in this project we would like to explore the Ru(II)-catalyzed [2+2+1] cycloadditions between alkynes and azides as nitrene sources to obtain pyrroles in a sustainable and efficient way.
Five-, six-, and seven-membered azaheterocycles are common nuclei in many drugs and pharmaceuticals. An attractive and sustainable strategy to their synthesis is based on metal-catalyzed cycloadditions of easily available partners. Thus, thermal and/or photoirradiated metal -(Co(I), Rh (I), Ru(II), Fe(II))- catalyzed [2+2+2] cycloadditions of alkynes and nitriles have been widely studied and successfully applied to the synthesis of pyridines. However, access to the pyrrole ring through metal-catalyzed [2+2+1] cycloadditions of readily available unsaturated partners has been more restricted. Having in mind the advantages of ruthenium over other transition metals and the availability of azides as nitrene precursors, in this project we would like to explore the Ru(II)-catalyzed [2+2+1] cycloadditions between alkynes and azides as nitrene sources to obtain pyrroles in a sustainable and efficient way.
Direction
SAA RODRIGUEZ, CARLOS EUGENIO (Tutorships)
VARELA CARRETE, JESUS ANGEL (Co-tutorships)
SAA RODRIGUEZ, CARLOS EUGENIO (Tutorships)
VARELA CARRETE, JESUS ANGEL (Co-tutorships)
Court
VARELA CARRETE, JESUS ANGEL (Chairman)
Vela Gallego, Sonia (Secretary)
Martínez del Campo, Teresa (Member)
VARELA CARRETE, JESUS ANGEL (Chairman)
Vela Gallego, Sonia (Secretary)
Martínez del Campo, Teresa (Member)
Development of a ceramic monolithic catalyst surface functionalized with MOF(Pd) and sodium silicate composite. Application in the synthesis of isatin type drugs.
Authorship
R.B.C.
Master's Degree in Chemical Research and Industrial Chemistry
R.B.C.
Master's Degree in Chemical Research and Industrial Chemistry
Defense date
07.18.2024 09:30
07.18.2024 09:30
Summary
Currently, due to environmental considerations, catalysis has gained even greater relevance than before, becoming one of the main sources of advancements in our society. Our research team developed a previous cermet catalyst based on Pd and alumina . The design of this research aims to improve the limitations of previously developed ceramic monolithic catalysts, where the necessary sintering process in a furnace at one thousand 1500 degrees Celsius eliminates much of the surface porosity. This review focuses on the synthesis of a catalytic system, using a silica monolith obtained through 3D printing. This system was functionalized with the MOF ZIF8 on the surface via direct impregnation techniques and subsequent functionalization with palladium nanoparticles and sodium silicate. Finally, the surface composite of the monolith was calcined, creating a nanoporous surface system with immobilized palladium. Using scanning electron microscopy, we observed the different stages of impregnation. Additionally, an X ray diffraction analysis was conducted to confirm the identity of the MOF, verifying it was ZIF 8. Furthermore, EDS analysis confirmed the presence of the various elements in the system. Subsequently, the final system was evaluated by synthesizing isatin type biomolecules. The biomolecules were characterized by mass spectrometry and nuclear magnetic resonance.
Currently, due to environmental considerations, catalysis has gained even greater relevance than before, becoming one of the main sources of advancements in our society. Our research team developed a previous cermet catalyst based on Pd and alumina . The design of this research aims to improve the limitations of previously developed ceramic monolithic catalysts, where the necessary sintering process in a furnace at one thousand 1500 degrees Celsius eliminates much of the surface porosity. This review focuses on the synthesis of a catalytic system, using a silica monolith obtained through 3D printing. This system was functionalized with the MOF ZIF8 on the surface via direct impregnation techniques and subsequent functionalization with palladium nanoparticles and sodium silicate. Finally, the surface composite of the monolith was calcined, creating a nanoporous surface system with immobilized palladium. Using scanning electron microscopy, we observed the different stages of impregnation. Additionally, an X ray diffraction analysis was conducted to confirm the identity of the MOF, verifying it was ZIF 8. Furthermore, EDS analysis confirmed the presence of the various elements in the system. Subsequently, the final system was evaluated by synthesizing isatin type biomolecules. The biomolecules were characterized by mass spectrometry and nuclear magnetic resonance.
Direction
Coelho Cotón, Alberto José (Tutorships)
AMORIN LOPEZ, MANUEL (Co-tutorships)
Coelho Cotón, Alberto José (Tutorships)
AMORIN LOPEZ, MANUEL (Co-tutorships)
Court
Sanmartin Matalobos, Jesus (Coordinator)
CID FERNANDEZ, MARIA MAGDALENA (Chairman)
Bermúdez García, Juan Manuel (Secretary)
GULIAS COSTA, MOISES (Member)
Sanmartin Matalobos, Jesus (Coordinator)
CID FERNANDEZ, MARIA MAGDALENA (Chairman)
Bermúdez García, Juan Manuel (Secretary)
GULIAS COSTA, MOISES (Member)
Pyrazol containing supramolecular polymers: towards the preparation of chiro-luminescent metallo-supramolecular architectures
Authorship
D.N.P.
Master in Organic Chemistry (3ª ed)
D.N.P.
Master in Organic Chemistry (3ª ed)
Defense date
07.18.2024 09:00
07.18.2024 09:00
Summary
Supramolecular polymers, bonded by non-covalent interactions such as hydrogen bonds and Van der Waals forces, exhibit unique and dynamic properties. The incorporation of metal ions introduces characteristics like phosphorescence. This work focuses on the synthesis and study of the self-assembly of pyrazole-based ligands, which combine self-assembly and metal coordination units. The designed molecules have two benzamides linked by an ethyl chain, introducing chirality to analyze its effect on self-assembly and polymer formation. One of the benzamides has a trisubstitution of O-dodecyl chains, which act as a solubilizer and provide hydrophobicity to the ligand. The coordinating part of the monomer is ethynyl-pyrazole. Self-assembly was studied using spectroscopic techniques such as NMR (Nuclear Magnetic Resonance), FT-IR (Fourier-transform infrared spectroscopy), UV-Vis (ultraviolet-visible spectroscopy), ECD (electronic circular dichroism), fluorescence, and microscopy techniques such as SEM (scanning electron microscopy) and AFM (atomic force microscopy). Preliminary studies reveal fibrous structures whose chirality can be controlled by the point chirality of the building block. Future research will explore coordination with metal ions to form metallo-supramolecular polymers.
Supramolecular polymers, bonded by non-covalent interactions such as hydrogen bonds and Van der Waals forces, exhibit unique and dynamic properties. The incorporation of metal ions introduces characteristics like phosphorescence. This work focuses on the synthesis and study of the self-assembly of pyrazole-based ligands, which combine self-assembly and metal coordination units. The designed molecules have two benzamides linked by an ethyl chain, introducing chirality to analyze its effect on self-assembly and polymer formation. One of the benzamides has a trisubstitution of O-dodecyl chains, which act as a solubilizer and provide hydrophobicity to the ligand. The coordinating part of the monomer is ethynyl-pyrazole. Self-assembly was studied using spectroscopic techniques such as NMR (Nuclear Magnetic Resonance), FT-IR (Fourier-transform infrared spectroscopy), UV-Vis (ultraviolet-visible spectroscopy), ECD (electronic circular dichroism), fluorescence, and microscopy techniques such as SEM (scanning electron microscopy) and AFM (atomic force microscopy). Preliminary studies reveal fibrous structures whose chirality can be controlled by the point chirality of the building block. Future research will explore coordination with metal ions to form metallo-supramolecular polymers.
Direction
FREIRE IRIBARNE, FELIX MANUEL (Tutorships)
RODRIGUEZ RIEGO, RAFAEL (Co-tutorships)
FREIRE IRIBARNE, FELIX MANUEL (Tutorships)
RODRIGUEZ RIEGO, RAFAEL (Co-tutorships)
Court
VARELA CARRETE, JESUS ANGEL (Chairman)
Vela Gallego, Sonia (Secretary)
Martínez del Campo, Teresa (Member)
VARELA CARRETE, JESUS ANGEL (Chairman)
Vela Gallego, Sonia (Secretary)
Martínez del Campo, Teresa (Member)
Development of a new quantitative method for determining the degree of curing of melamine
Authorship
C.P.B.
Master's Degree in Chemical Research and Industrial Chemistry
C.P.B.
Master's Degree in Chemical Research and Industrial Chemistry
Defense date
07.18.2024 09:00
07.18.2024 09:00
Summary
Finsa is a company in the wood sector dedicated to the manufacture of board, decorative panels, furniture, countertops and laminate flooring. All products must guarantee a quality, for this a series of controls are carried out that allow us to determine the parameters of interest, to ensure that the final product complies with the application for which it was manufactured. The three parameters studied in this Final Master’s Work developed in the Department of Research, Development and Innovation are: the degree of curing melamine present in the resin used for the impregnation of decorative paper, the concentration of melamine present in the resin used as an adhesive in the manufacture of panels and the concentration of phosphates present in flame retardant boards. As for the determination of the degree of curing of melamine, the aim is to determine spectrophotometrically the degree of reticulation of the melamine monomer present in the impregnation resin of decorative paper, pressed on a panel. The importance of this determination lies in the need to ensure a quality in the manufacture of the panels, these must meet a number of properties depending on the applications for which they were manufactured. The second of the methods developed is the determination of melamine on board, where melamine is extracted by acid digestion and then determined spectrophotometrically. This method was developed to determine the amount of melamine resin used in board manufacturing. In this way, this parameter can be adjusted which directly influences the production costs. Finally, in the determination of phosphates in flame retardant board, acid digestion is also used for the extraction of phosphates and a complex reagent is added that forms an adduct with the yellow phosphate that is determined spectrophotometrically. Fire-retardant boards, thanks to the presence of phosphate salts do not burn, but create a layer of carbon on the surface that prevents the spread of the flame. These boards must comply with a number of regulations, so it is important to be able to determine the amount of phosphates.
Finsa is a company in the wood sector dedicated to the manufacture of board, decorative panels, furniture, countertops and laminate flooring. All products must guarantee a quality, for this a series of controls are carried out that allow us to determine the parameters of interest, to ensure that the final product complies with the application for which it was manufactured. The three parameters studied in this Final Master’s Work developed in the Department of Research, Development and Innovation are: the degree of curing melamine present in the resin used for the impregnation of decorative paper, the concentration of melamine present in the resin used as an adhesive in the manufacture of panels and the concentration of phosphates present in flame retardant boards. As for the determination of the degree of curing of melamine, the aim is to determine spectrophotometrically the degree of reticulation of the melamine monomer present in the impregnation resin of decorative paper, pressed on a panel. The importance of this determination lies in the need to ensure a quality in the manufacture of the panels, these must meet a number of properties depending on the applications for which they were manufactured. The second of the methods developed is the determination of melamine on board, where melamine is extracted by acid digestion and then determined spectrophotometrically. This method was developed to determine the amount of melamine resin used in board manufacturing. In this way, this parameter can be adjusted which directly influences the production costs. Finally, in the determination of phosphates in flame retardant board, acid digestion is also used for the extraction of phosphates and a complex reagent is added that forms an adduct with the yellow phosphate that is determined spectrophotometrically. Fire-retardant boards, thanks to the presence of phosphate salts do not burn, but create a layer of carbon on the surface that prevents the spread of the flame. These boards must comply with a number of regulations, so it is important to be able to determine the amount of phosphates.
Direction
Sanmartin Matalobos, Jesus (Tutorships)
Sanmartin Matalobos, Jesus (Tutorships)
Court
Sanmartin Matalobos, Jesus (Coordinator)
SOTO CASTINHEIRA, MANUEL (Chairman)
BELLO BUGALLO, PASTORA MARIA (Secretary)
Leao Martins, José Manuel (Member)
Sanmartin Matalobos, Jesus (Coordinator)
SOTO CASTINHEIRA, MANUEL (Chairman)
BELLO BUGALLO, PASTORA MARIA (Secretary)
Leao Martins, José Manuel (Member)
Engineering Artificial Enzymes for non natural chemistry
Authorship
C.L.D.A.B.
Master in Chemistry at the Interface of Biology and Materials Science
C.L.D.A.B.
Master in Chemistry at the Interface of Biology and Materials Science
Defense date
02.12.2023 10:00
02.12.2023 10:00
Summary
The use of enzymes to promote novel abiological transformations is a longstanding goal in synthetic chemistry. One of the most successful approaches involves the use of artificial metalloenzymes (ArMs), where synthetic metal complexes are incorporated into a biomolecular scaffold, combining enzymatic and transition metal catalysis. This integration offers catalytic efficiency and selectivity under mild conditions similar to natural enzymes, along with advantages such as versatility, tunability, and alternative substrate specificity. In this project, we explore the formation of artificial metalloenzymes by combining ruthenium (II) and (IV) organometallic complexes with the LmrR protein through supramolecular assembly. The binding efficiency of the Ru complexes with LmrR is evaluated using fluorescence spectroscopy, and the catalytic activity of the resulting biohybrids is examined in a deallylation reaction model. Preliminary studies on the asymmetric version of this reaction are conducted. In recent years, the use of light to promote enzymatic activities, also known as photobiocatalysis, have emerged as a promising approach to promote novel activities unknown in nature. Combining biocatalysis with photocatalysis enables selective transformations and offers advantages such as new reactivity, high enantioselectivity, and greener synthesis. In this project, the focus is on developing artificial photoenzymes by incorporating abiotic photocatalysts, such as the benzophenone alanine non canonical amino acid (BpA), into de novo alpha helix proteins. To ensure the correct photocatalytic conditions for the reaction with the benzophenone alanine non canonical amino acid, we will use the recently published enantioselective [2+2] cycloaddition catalyzed by an artificial metalloenzyme based on the protein LmrR and the BpA non canonical amino acid as a benchmark reaction. Both approaches contribute to the exploration of innovative solutions in the field of synthetic chemistry. Overall, this study seeks to design and develop new artificial photo and metallo enzymes with potential applications in new to nature catalytic reactions.
The use of enzymes to promote novel abiological transformations is a longstanding goal in synthetic chemistry. One of the most successful approaches involves the use of artificial metalloenzymes (ArMs), where synthetic metal complexes are incorporated into a biomolecular scaffold, combining enzymatic and transition metal catalysis. This integration offers catalytic efficiency and selectivity under mild conditions similar to natural enzymes, along with advantages such as versatility, tunability, and alternative substrate specificity. In this project, we explore the formation of artificial metalloenzymes by combining ruthenium (II) and (IV) organometallic complexes with the LmrR protein through supramolecular assembly. The binding efficiency of the Ru complexes with LmrR is evaluated using fluorescence spectroscopy, and the catalytic activity of the resulting biohybrids is examined in a deallylation reaction model. Preliminary studies on the asymmetric version of this reaction are conducted. In recent years, the use of light to promote enzymatic activities, also known as photobiocatalysis, have emerged as a promising approach to promote novel activities unknown in nature. Combining biocatalysis with photocatalysis enables selective transformations and offers advantages such as new reactivity, high enantioselectivity, and greener synthesis. In this project, the focus is on developing artificial photoenzymes by incorporating abiotic photocatalysts, such as the benzophenone alanine non canonical amino acid (BpA), into de novo alpha helix proteins. To ensure the correct photocatalytic conditions for the reaction with the benzophenone alanine non canonical amino acid, we will use the recently published enantioselective [2+2] cycloaddition catalyzed by an artificial metalloenzyme based on the protein LmrR and the BpA non canonical amino acid as a benchmark reaction. Both approaches contribute to the exploration of innovative solutions in the field of synthetic chemistry. Overall, this study seeks to design and develop new artificial photo and metallo enzymes with potential applications in new to nature catalytic reactions.
Direction
Mascareñas Cid, Jose Luis (Tutorships)
Mascareñas Cid, Jose Luis (Tutorships)
Court
RIVADULLA FERNANDEZ, JOSE FRANCISCO (Chairman)
NAPPI , MANUEL (Secretary)
PELAZ GARCIA, BEATRIZ (Member)
RIVADULLA FERNANDEZ, JOSE FRANCISCO (Chairman)
NAPPI , MANUEL (Secretary)
PELAZ GARCIA, BEATRIZ (Member)
Unveiling biomolecule stabilization in Deep Eutectic Solvents: synthesis, solubilization, and characterization of peptide models
Authorship
A.P.M.
Master in Organic Chemistry (3ª ed)
A.P.M.
Master in Organic Chemistry (3ª ed)
Defense date
07.18.2024 09:00
07.18.2024 09:00
Summary
The development of functional environments capable of preserving biomolecules and rationally controlling their behavior poses a great challenge in chemistry. For this purpose, Deep Eutectic Solvents (DESs) have emerged as promising tools. DESs are anhydrous mixtures of an organic salt with a neutral hydrogen bond donor at the eutectic ratio, yielding a depression in the melting point compared to their pure constituents that allows the system to remain liquid at room temperature. Their properties are dictated by intermolecular interactions, such as electrostatic, Van der Waals and hydrogen bonding, and they can be modulated through changes in the precursors. Previous investigations have shown the ability of a few DESs to support protein folding and protect them against degradation. However, little is known about their ability to control protein behavior through changes in the solvent properties. In this study, we demonstrate the ability of compositionally designed DESs to stabilize different protein conformations in anhydrous conditions. Several choline chloride-based DESs with tailored hydrogen bonding capabilities were formulated in combination with either acetic acid, glycerol, and urea at a mole ratio of 1:2. Trp-Cage was selected as model protein since it is the smallest artificial protein with defined secondary and tertiary structure discovered till date. The mini protein was synthesized using solid-phase peptide synthesis (SPPS) and successfully solubilized in the DESs. By means of ultraviolet-visible spectroscopy (UV-Vis) and circular dichroism (CD) spectroscopy, our results demonstrate the ability of DESs to capture different conformations in relation to the changes in solvent constituents, ranging from a near-native fold with high populations of alpha helix in the glycerol-based DES to fully unfolded domains in the urea-based solvent. In addition, the reconstitution of the protein in aqueous buffer prompts the retrieval of the native conformation, demonstrating the ability of DESs to transiently modulate protein behavior. Altogether, our study shows the potential of DESs as tailorable environments for protein stabilization in non-aqueous conditions. As such, this study constitutes a proof-of-concept for future chemical and pharmaceutical technologies exploiting biomolecule stabilization using these synthetically accessible and bioderived environments.
The development of functional environments capable of preserving biomolecules and rationally controlling their behavior poses a great challenge in chemistry. For this purpose, Deep Eutectic Solvents (DESs) have emerged as promising tools. DESs are anhydrous mixtures of an organic salt with a neutral hydrogen bond donor at the eutectic ratio, yielding a depression in the melting point compared to their pure constituents that allows the system to remain liquid at room temperature. Their properties are dictated by intermolecular interactions, such as electrostatic, Van der Waals and hydrogen bonding, and they can be modulated through changes in the precursors. Previous investigations have shown the ability of a few DESs to support protein folding and protect them against degradation. However, little is known about their ability to control protein behavior through changes in the solvent properties. In this study, we demonstrate the ability of compositionally designed DESs to stabilize different protein conformations in anhydrous conditions. Several choline chloride-based DESs with tailored hydrogen bonding capabilities were formulated in combination with either acetic acid, glycerol, and urea at a mole ratio of 1:2. Trp-Cage was selected as model protein since it is the smallest artificial protein with defined secondary and tertiary structure discovered till date. The mini protein was synthesized using solid-phase peptide synthesis (SPPS) and successfully solubilized in the DESs. By means of ultraviolet-visible spectroscopy (UV-Vis) and circular dichroism (CD) spectroscopy, our results demonstrate the ability of DESs to capture different conformations in relation to the changes in solvent constituents, ranging from a near-native fold with high populations of alpha helix in the glycerol-based DES to fully unfolded domains in the urea-based solvent. In addition, the reconstitution of the protein in aqueous buffer prompts the retrieval of the native conformation, demonstrating the ability of DESs to transiently modulate protein behavior. Altogether, our study shows the potential of DESs as tailorable environments for protein stabilization in non-aqueous conditions. As such, this study constitutes a proof-of-concept for future chemical and pharmaceutical technologies exploiting biomolecule stabilization using these synthetically accessible and bioderived environments.
Direction
MONTENEGRO GARCIA, JAVIER (Tutorships)
SANCHEZ FERNANDEZ, ADRIAN (Co-tutorships)
MONTENEGRO GARCIA, JAVIER (Tutorships)
SANCHEZ FERNANDEZ, ADRIAN (Co-tutorships)
Court
VARELA CARRETE, JESUS ANGEL (Chairman)
Vela Gallego, Sonia (Secretary)
Martínez del Campo, Teresa (Member)
VARELA CARRETE, JESUS ANGEL (Chairman)
Vela Gallego, Sonia (Secretary)
Martínez del Campo, Teresa (Member)
Separation of proteins by offgel electrophoresis in algae samples exposed to silver nanoparticles
Authorship
S.G.B.
Master's Degree in Chemical Research and Industrial Chemistry
S.G.B.
Master's Degree in Chemical Research and Industrial Chemistry
Defense date
07.18.2024 09:00
07.18.2024 09:00
Summary
The search for new methods of extracting proteins from algae is a current topic of interest aimed at finding new protein sources and thus meeting the growing nutritional demand. Like algae proteins, Ag nanoparticles (AgNPs), which are among the most widely used, are also a subject of study due to their multiple applications in fields such as industry and biomedicine, leading to an increase in their presence in the environment. Therefore, this work aims to analyze proteins and their Ag content in two species of red and green algae (Palmaria palmata and Ulva sp.) previously exposed to 1,0 mg/L of 15 nm PVP AgNPs for 28 days. First, two methods for protein extraction are compared: enzymatic extraction with Macerozyme R 10 and phenol extraction, separating the resulting protein pellets by offgel electrophoresis based on their isoelectric point (pI). Next, the protein fractions obtained from offgel electrophoresis are analyzed by Lab On a Chip (LOC) electrophoresis, achieving separation by molecular weight and quantification by fluorescence. Based on the results obtained, it is concluded that the phenol extraction method achieves a higher yield of proteins. Later, samples are prepared with liquid N2 to increase the amount of protein extracts. Finally, the Ag content present in the protein fractions obtained by offgel electrophoresis is measured using Electrothermal Atomic Absorption Spectrometry (ETAAS). The determination method was optimized, and analytical characteristics were studied, demonstrating its accuracy and precision. The results show Ag content in 17 and 20 to 24 offgel protein fractions (pI 8.1 to 10) with a concentration range of 16.2 microgram/litre to 131.8 micrograme/litre for Palmaria palmata. In Ulva sp. The results were similar, with Ag content in fractions 19 to 24 (pI 8.67 to 10) and concentrations ranging from 20.83 microgram/litre to 186.45 microgram/litre.
The search for new methods of extracting proteins from algae is a current topic of interest aimed at finding new protein sources and thus meeting the growing nutritional demand. Like algae proteins, Ag nanoparticles (AgNPs), which are among the most widely used, are also a subject of study due to their multiple applications in fields such as industry and biomedicine, leading to an increase in their presence in the environment. Therefore, this work aims to analyze proteins and their Ag content in two species of red and green algae (Palmaria palmata and Ulva sp.) previously exposed to 1,0 mg/L of 15 nm PVP AgNPs for 28 days. First, two methods for protein extraction are compared: enzymatic extraction with Macerozyme R 10 and phenol extraction, separating the resulting protein pellets by offgel electrophoresis based on their isoelectric point (pI). Next, the protein fractions obtained from offgel electrophoresis are analyzed by Lab On a Chip (LOC) electrophoresis, achieving separation by molecular weight and quantification by fluorescence. Based on the results obtained, it is concluded that the phenol extraction method achieves a higher yield of proteins. Later, samples are prepared with liquid N2 to increase the amount of protein extracts. Finally, the Ag content present in the protein fractions obtained by offgel electrophoresis is measured using Electrothermal Atomic Absorption Spectrometry (ETAAS). The determination method was optimized, and analytical characteristics were studied, demonstrating its accuracy and precision. The results show Ag content in 17 and 20 to 24 offgel protein fractions (pI 8.1 to 10) with a concentration range of 16.2 microgram/litre to 131.8 micrograme/litre for Palmaria palmata. In Ulva sp. The results were similar, with Ag content in fractions 19 to 24 (pI 8.67 to 10) and concentrations ranging from 20.83 microgram/litre to 186.45 microgram/litre.
Direction
PEÑA VAZQUEZ, ELENA MARIA (Tutorships)
BARCIELA ALONSO, Ma CARMEN (Co-tutorships)
PEÑA VAZQUEZ, ELENA MARIA (Tutorships)
BARCIELA ALONSO, Ma CARMEN (Co-tutorships)
Court
Sanmartin Matalobos, Jesus (Coordinator)
YEBRA BIURRUN, MARIA DEL CARMEN (Chairman)
Prieto Jiménez, Inmaculada (Secretary)
Carlosena Zubieta, Alatzne (Member)
Sanmartin Matalobos, Jesus (Coordinator)
YEBRA BIURRUN, MARIA DEL CARMEN (Chairman)
Prieto Jiménez, Inmaculada (Secretary)
Carlosena Zubieta, Alatzne (Member)
Distal activation of C H bonds by organometallic catalysis
Authorship
M.J.M.S.
Master in Organic Chemistry (3ª ed)
M.J.M.S.
Master in Organic Chemistry (3ª ed)
Defense date
07.18.2024 09:00
07.18.2024 09:00
Summary
Borylation reactions are among the most commonly utilized C H activation reactions in organic chemistry due to the ease of derivatizing the resulting products. For instance, these compounds serve as the initial substrates for Suzuki reactions, which transforms C B bonds into C C bonds. This TFM focuses on the diastereoselective ortho-borylation of ferrocene derivatives. Ferrocenes are crucial templates in various branches of organic chemistry, particularly as ligands or catalyst for asymmetric catalysis. In this study, chiral amides attached to ferrocenes were used to influence the diastereoselectivity of an iridium catalyzed borylation. Additionally, studies were conducted using chiral benzamides to investigate the effect of the chiral auxiliary on the reaction outcomes.
Borylation reactions are among the most commonly utilized C H activation reactions in organic chemistry due to the ease of derivatizing the resulting products. For instance, these compounds serve as the initial substrates for Suzuki reactions, which transforms C B bonds into C C bonds. This TFM focuses on the diastereoselective ortho-borylation of ferrocene derivatives. Ferrocenes are crucial templates in various branches of organic chemistry, particularly as ligands or catalyst for asymmetric catalysis. In this study, chiral amides attached to ferrocenes were used to influence the diastereoselectivity of an iridium catalyzed borylation. Additionally, studies were conducted using chiral benzamides to investigate the effect of the chiral auxiliary on the reaction outcomes.
Direction
GULIAS COSTA, MOISES (Tutorships)
Mascareñas Cid, Jose Luis (Co-tutorships)
GULIAS COSTA, MOISES (Tutorships)
Mascareñas Cid, Jose Luis (Co-tutorships)
Court
VARELA CARRETE, JESUS ANGEL (Chairman)
Vela Gallego, Sonia (Secretary)
Martínez del Campo, Teresa (Member)
VARELA CARRETE, JESUS ANGEL (Chairman)
Vela Gallego, Sonia (Secretary)
Martínez del Campo, Teresa (Member)