Artículos (Química Orgánica y Farmacéutica)

URI permanente para esta colecciónhttps://hdl.handle.net/11441/11085

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Efficient Strategy to Synthesize Tunable pH-Responsive Hybrid Micelles Based on Iron Oxide and Gold Nanoparticles
(American Chemical Society, 2024) Gimeno Ferrero, Raúl; Rodríguez de Jesús, Javier; Pernia Leal, Manuel; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica; Ministerio de Ciencia, Innovación y Universidades (MICINN). España; Junta de Andalucía
The preparation of multifunctional nanomaterials based on inorganic nanoparticles with organic materials has emerged as a promising strategy for the development of new nanomedicines for in vitro and in vivo biomedical applications. Here, we synthesized pH-responsive hybrid inorganic micelles by combining a novel pH-responsive amphiphilic molecule with hydrophobic payloads. This amphiphile was synthesized in a one-pot reaction and self-assembled readily into micelles under acidic pH conditions. In the presence of hydrophobic NP payloads such as AuNPs or IONPs, the amphiphile self-organized around them through hydrophobic interactions, resulting in the formation of colloidally stable hybrid micelles. The size of the hydrophobic NPs determined the pH-response of the inorganic hybrid micelles, which is tuned from pH 7 to 11 for our pH-responsive amphiphilic molecule. This achievement represents a novel approach for the synthesis of tunable pH-responsive hybrid micelles based on inorganic NPs for biomedical imaging, hyperthermia treatment, and also drug delivery nanosystems.
Findings and perspectives of β-Ti alloys with biomedical applications: Exploring beyond biomechanical and biofunctional behaviour
(Elsevier, 2024-12) Elhadad, Amir A.; Romero-Resendiz, Liliana; Rossi, Mariana Correa; Rodríguez-Albelo, Luisa Marleny; Lascano, Sheila; Afonso, Conrado R.M.; Alcudia Cruz, Ana; Amigó, Vicente; Torres Hernández, Yadir; Universidad de Sevilla. Departamento de Ingeniería y Ciencia de los Materiales y del Transporte; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica; Ministerio de Ciencia e Innovación (MICIN). España; Universidad de Sevilla. FQM: 408: Química Farmacéutica Aplicada; Universidad de Sevilla. TEP123: Metalurgia e Ingeniería de los Materiales
Early implant failure and bone resorption may occur in load-bearing conditions as a result of stress shielding brought on by a mismatch in the bone-Ti-implant modulus. A review with a novel multidisciplinary perspective is proposed in this work, which considers recent developments of β-Titanium alloys and new trends in novel microstructures, processing techniques, properties of dense and porous substrates, as well as the relationship between all these aspects and performance in service, in terms of improved its biomechanical and bio-functional balance. In addition to highlighting several modern and historical uses for Ti alloys, this review covers many cutting-edge novel β-Ti alloys and uses that promise to exceed historical standards. Also, it deepens through several important properties of these alloys, including toxicity of alloying elements, phase stability, thermo-mechanical processing, heat treatment, surface, and stress-induced modifications. The stiffness, hardness, fatigue and wear resistance, corrosion behaviour, biocompatibility, and manufacturing and surface modification effects on these parameters are also emphasized. In-vitro and in-vivo assays have been added to highlight important aspects of bioactivity and antibacterial behaviour, and future significant research areas are suggested along with new techniques to ensure the successful clinical application of β-Ti alloys.
Unraveling the Formation of Ternary AgCuSe Crystalline Nanophases and Their Potential as Antibacterial Agents
(American Chemical Society, 2024-10-09) Lin, Mengxi; Estruch Blasco, Manel; Pernia Leal, Manuel; Pajuelo Domínguez, Eloísa; Rodríguez, Laura; Figuerola, Albert; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica; Universidad de Sevilla. Departamento de Microbiología y Parasitología; Ministerio de Ciencia, Innovación y Universidades (MICINN). España; Dutch Research Council (NWO); Generalitat de Catalunya; Junta de Andalucía; Universidad de Sevilla
AgCuSe nanoparticles could contribute to the growth of strongly light-absorbing thin films and solids with fast ion mobility, among other potential properties. Nevertheless, few methods have been developed so far for the synthesis of AgCuSe nanoparticles, and those reported deliver nanostructures with relatively large sizes and broad size and shape distributions. In this work, a colloidal cation exchange method is established for the easy synthesis of AgCuSe NPs with ca. 8 nm diameters and narrow size dispersion. Notably, in this lower size range the conucleation and growth of two stoichiometric ternary compounds are generally observed, namely the well-known eucairite AgCuSe compound and the novel fischesserite-like Ag3CuSe2 phase, the latter being less thermodynamically stable as predicted computationally and assessed experimentally. An optimal range of Cu/Ag precursor molar ratio has been identified to ensure the growth of ternary nanoparticles and, more specifically, that of the metastable Ag3CuSe2 nanophase isolated for the first occasion. The attained size range for the material paves the way for utilizing AgCuSe nanoparticles in new ways within the field of biomedicine: the results obtained here confirm the antibacterial activity of the new AgxCuySez nanoparticles against Gram-positive bacteria, with significantly low values of the minimal inhibitory concentration. © 2024 The Authors. Published by American Chemical Society.
Engineering amphiphilic alkenyl lipids for self-assembly in functional hybrid nanostructures
(Springer Nature, 2024-11-21) Gimeno Ferrero, Raúl; Valdivia Giménez, Victoria Esther; Fernández Fernández, Inmaculada; García-Martín, María Luisa; Pernia Leal, Manuel; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica; Ministerio de Ciencia, Innovación y Universidades (MICINN). España; Junta de Andalucía
The development of biocompatible hybrid nanosystems for advanced functional applications presents significant challenges to the research community. Key obstacles include the poor solubility of these nanosystems in water and the difficulty of precisely controlling their nanostructure dimensions and composition. A promising approach to overcoming these challenges is the self-assembly of surfactant-based building blocks into well-ordered hybrid nanostructures. In this study, we explore the relationship between structure and self-assembly in novel low molecular weight amphiphilic molecules to produce stable and biocompatible hybrid nanostructures. We investigated the self-assembly behavior of two families of amphiphiles derived from alkenyl lipids with one or two double bonds, leading to distinct hybrid supramolecular structures facilitated by the incorporation of hydrophobic iron oxide nanoparticles (IONPs) as templates. The presence of double bonds in the lipid tail and the morphology of the amphiphile influence the arrangement on the hydrophobic NPs. Amphiphiles with a single double bond in the lipid tail form highly water-soluble, well-ordered micellar-like structures on the IONP surfaces, while those with two double bonds create disordered lipid nanoparticles. Furthermore, these amphiphilic molecules can self-organize into higher-order hybrid supramolecular structures, such as vesicles, with potential applications in magnetic resonance imaging (MRI).
Properties of polyplexes formed between a cationic polymer derived from l-arabinitol and nucleic acids
(Royal Society of Chemistry, 2021-05-14) Pérez Alfonso, David; López López, Manuel; López-Cornejo, María del Pilar; Romero Azogil, Lucía; Benito Hernández, Elena María; García Martín, María de Gracia; García Calderón, Clara Beatriz; Valle Rosado, Iván; Romero Balestra, Fernando; Huertas Sánchez, Pablo; García Calderón, Margarita; Moyá Morán, María Luisa; Universidad de Sevilla. Departamento de Química Física; Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica; Universidad de Sevilla. Departamento de Genética; Junta de Andalucía; Universidad de Sevilla; Ministerio de Ciencia, Innovación y Universidades (MICINN). España; European Union (UE)
In this work a sugar-based cationic polymer derived from L-arabinitol, PUArab, was prepared and its interactions with the linear calf thymus DNA and with the circular plasmid pEGFP-C1 were investigated at different N/P ratios. The polyplexes were characterized by using several techniques. For both nucleic acids, a charge inversion was observed, together with a conformational change from a coiled structure to a more compacted one. However, the N/P ratio required to observe the DNA condensation depended on the nucleic acid architecture. PUArab presents low toxicity in several cell lines. The transfection efficiency, TE, of the PUArab/pEGFP-C1 polyplexes was investigated at several N/P ratios in order to study their potential as vectors in gene transfection.
Stereoselective Synthesis of Chiral C2-Symmetric 1,3- and 1,5-Bis-Sulfoxides Guided by the Horeau Principle: Understanding the Influence of the Carbon Chain Nature in Its Ability for Metal Coordination
(ACS Publications, 2024-10-02) Moreno Rodríguez, Nazaret; Prieto Ramírez, Luis Alberto; Valdivia Giménez, Victoria Esther; Recio Jiménez, Rocío; Fernández Fernández, Inmaculada; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica; European Union (UE); Junta de Andalucía; Ministerio de Ciencia, Innovación y Universidades (MICINN). España
The stereoselective synthesis of two distinct types of C2-symmetric chiral bis-sulfoxides, 1,3- and 1,5-bis(sulfinyl) derivatives, has been achieved based on the DAG methodology. The 1,5-bis(sulfinyl) derivatives constitute a new family of tridentate chiral ligands thanks to the presence of an additional sulfenyl or sulfinyl group in the carbon chain acting as a bridge. A systematic development and optimization of two synthetic routes, one for each ligand family, have been undertaken, highlighting the strategic utilization of Horeau’s law to enhance enantioselectivity. Additionally, palladium (Pd) and ruthenium (Ru) complexes derived from the synthesized bis-sulfoxides were prepared, and their structures were elucidated through spectroscopic analysis. Isolation of Pd(II) complexes involving 1,3-bis-sulfoxides was exclusively achieved using trifluoroacetates as coligands. In the case of Ru(II) complexes, the trans geometry could be determined for 1,3-bis-sulfoxides. The introduction of a third sulfur atom as a coordinating element in the 1,5-bis(sulfinyl) derivatives facilitates the formation of two distinct tricoordinated Ru(II) complexes. The structure of these complexes is intricately influenced by the oxidation state adopted by the central sulfur on the chain, whether as a thioether or as a sulfoxide.
Advanced interpenetrating polymer networks for innovative gastroretentive formulations targeting Helicobacter pylori gastric colonization
(Elsevier, 2024-09) Grosso, Roberto; Benito Hernández, Elena María; Carbajo Gordillo, Ana Isabel; Díaz, Manuel Jesús; García Martín, María de Gracia; Paz Báñez, María Violante de; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica; Ministerio de Ciencia, Innovación y Universidades (MICINN). España; Agencia Estatal de Investigación. España; European Union (UE); Junta de Andalucía
The escalating challenges of Helicobacter pylori-induced gastric complications, driven by rising antibiotic resistance and persistent cancer risks, underscore the demand for innovative therapeutic strategies. This study addresses this urgency through the development of tailored semi-interpenetrating polymer networks (semi-IPN) serving as gastroretentive matrices for amoxicillin (AMOX). They are biodegradable, absorb significant volume of simulated gastric fluid (swelling index > 360 %) and exhibit superporous microstructures, remarkable mucoadhesion, and buoyancy. The investigation includes assessment at pH 1.2 for comparative analysis with prior studies and, notably, at pH 5.0, reflecting the acidic environment in H. pylori-infected stomachs. The semi-IPN demonstrated gel-like structures, maintaining integrity throughout the 24-hour controlled release study, and disintegrating upon completing their intended function. Evaluated in gastroretentive drug delivery system performance, AMOX release at pH 1.2 and pH 5.0 over 24 h (10 %-100 %) employed experimental design methodology, elucidating dominant release mechanisms. Their mucoadhesive, buoyant, three-dimensional scaffold stability, and gastric biodegradability make them ideal for accommodating substantial AMOX quantities. Furthermore, exploring the inclusion of the potassium-competitive acid blocker (P-CAB) vonoprazan (VONO) in AMOX-loaded formulations shows promise for precise and effective drug delivery. This innovative approach has the potential to combat H. pylori infections, thereby preventing the gastric cancer induced by this pathogen.
Simultaneous Formation of Polyhydroxyurethanes and Multicomponent Semi-IPN Hydrogels
(MDPI, 2024) Carbajo Gordillo, Ana Isabel; Benito Hernández, Elena María; Galbis Fuster, Elsa; Grosso, R.; Iglesias Blanco, Nieves; Valencia, C.; Lucas Rodríguez, Ricardo; García Martín, María de Gracia; Paz Báñez, María Violante de; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica; Ministerio de Ciencia, Innovación y Universidades (MICINN). España; Junta de Andalucía
This study introduces an efficient strategy for synthesizing polyhydroxyurethane-based multicomponent hydrogels with enhanced rheological properties. In a single-step process, 3D materials composed of Polymer 1 (PHU) and Polymer 2 (PVA or gelatin) were produced. Polymer 1, a crosslinked polyhydroxyurethane (PHU), grew within a colloidal solution of Polymer 2, forming an interconnected network. The synthesis of Polymer 1 utilized a Non-Isocyanate Polyurethane (NIPU) methodology based on the aminolysis of bis(cyclic carbonate) (bisCC) monomers derived from 1-thioglycerol and 1,2-dithioglycerol (monomers A and E, respectively). This method, applied for the first time in Semi-Interpenetrating Network (SIPN) formation, demonstrated exceptional orthogonality since the functional groups in Polymer 2 do not interfere with Polymer 1 formation. Optimizing PHU formation involved a 20-trial methodology, identifying influential variables such as polymer concentration, temperature, solvent (an aprotic and a protic solvent), and the organo-catalyst used [a thiourea derivative (TU) and 1,8-diazabicyclo [5.4.0]undec-7-ene (DBU)]. The highest molecular weights were achieved under near-bulk polymerization conditions using TU-protic and DBU-aprotic as catalyst–solvent combinations. Monomer E-based PHU exhibited higher (Formula presented.) than monomer A-based PHU (34.1 kDa and 16.4 kDa, respectively). Applying the enhanced methodology to prepare 10 multicomponent hydrogels using PVA or gelatin as the polymer scaffold revealed superior rheological properties in PVA-based hydrogels, exhibiting solid-like gel behavior. Incorporating monomer E enhanced mechanical properties and elasticity (with loss tangent values of 0.09 and 0.14). SEM images unveiled distinct microstructures, including a sponge-like pattern in certain PVA-based hydrogels when monomer A was chosen, indicating the formation of highly superporous interpenetrated materials. In summary, this innovative approach presents a versatile methodology for obtaining advanced hydrogel-based systems with potential applications in various biomedical fields.
Synthesis of a New β-Galactosidase Inhibitor Displaying Pharmacological Chaperone Properties for GM1 Gangliosidosis
(MDPI, 2022) Clemente, Francesca; Martínez Bailén, Macarena; Matassini, Camilla; Morrone, Amelia; Falliano, Silvia; Caciotti, Anna; Paoli, Paolo; Goti, Andrea; Cardona, Francesca; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica
GM1 gangliosidosis is a rare lysosomal disease caused by the deficiency of the enzyme β-galactosidase (β-Gal; GLB1; E.C. 3.2.1.23), responsible for the hydrolysis of terminal β-galactosyl residues from GM1 ganglioside, glycoproteins, and glycosaminoglycans, such as keratan-sulfate. With the aim of identifying new pharmacological chaperones for GM1 gangliosidosis, the synthesis of five new trihydroxypiperidine iminosugars is reported in this work. The target compounds feature a pentyl alkyl chain in different positions of the piperidine ring and different absolute configurations of the alkyl chain at C-2 and the hydroxy group at C-3. The organometallic addition of a Grignard reagent onto a carbohydrate-derived nitrone in the presence or absence of a suitable Lewis Acid was exploited, providing structural diversity at C-2, followed by the ring-closure reductive amination step. An oxidation-reduction process allowed access to a different configuration at C-3. The N-pentyl trihydroxypiperidine iminosugar was also synthesized for the purpose of comparison. The biological evaluation of the newly synthesized compounds was performed on leucocyte extracts from healthy donors and identified two suitable β-Gal inhibitors, namely compounds 10 and 12. Among these, compound 12 showed chaperoning properties since it enhanced β-Gal activity by 40% when tested on GM1 patients bearing the p.Ile51Asn/p.Arg201His mutations.
GCase Enhancers: A Potential Therapeutic Option for Gaucher Disease and Other Neurological Disorders
(MDPI, 2022) Martínez Bailén, Macarena; Clemente, Francesca; Matassini, Camilla; Cardona, Francesca; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica
Pharmaceutical chaperones (PCs) are small compounds able to bind and stabilize misfolded proteins, allowing them to recover their native folding and thus their biological activity. In particular, lysosomal storage disorders (LSDs), a class of metabolic disorders due to genetic mutations that result in misfolded lysosomal enzymes, can strongly benefit from the use of PCs able to facilitate their translocation to the lysosomes. This results in a recovery of their catalytic activity. No PC for the GCase enzyme (lysosomal acid-β-glucosidase, or glucocerebrosidase) has reached the market yet, despite the importance of this enzyme not only for Gaucher disease, the most common LSD, but also for neurological disorders, such as Parkinson’s disease. This review aims to describe the efforts made by the scientific community in the last 7 years (since 2015) in order to identify new PCs for the GCase enzyme, which have been mainly identified among glycomimetic-based compounds.
Uso de herramientas activas para dinamizar el aula y mejorar el aprendizaje en la asignatura de Química Orgánica I
(Real e Ilustre Colegio Oficial de Farmacéuticos de Sevilla, 2023) Moreno Rodríguez, Nazaret; Valdivia Giménez, Victoria Esther; Recio Jiménez, Rocío; Vega Holm, Margarita; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica
El absentismo estudiantil, la dificultad para mantener la atención en clase y la falta de organización del trabajo diario fuera del aula son tres de los problemas más importantes a los que se enfrenta el profesorado universitario, sobre todo en asignaturas de los primeros cursos, consideradas por el alumnado como difíciles, como es el caso de la asignatura de Química Orgánica I (QOI) del Grado en Farmacia. En este trabajo se propone incentivar la atención de los estudiantes empleando la plataforma wooclap durante las clases teórico-prácticas de la asignatura de QOI y la mejora del trabajo individual de los alumnos fuera del aula mediante la realización de cuestionarios a través de Blackboard Collaborate ultra. Ambas propuestas pretenden mejorar la calidad del aprendizaje y fomentar la elección por parte del alumnado de la evaluación continua, contribuyendo a disminuir la tasa de suspensos y no presentados que caracteriza a la asignatura. Además, se presenta un modelo de evaluación de la utilidad de la propuesta de innovación planteada a través de un cuestionario anónimo, permitiendo la identificación de las principales fortalezas y debilidades del modelo aplicado y pudiéndose llevar a cabo ciclos de mejora.
Chemically Tuning Resveratrol for the Effective Killing of Gram- Positive Pathogens
(ACS, 2022) Cebrián, Rubén; Li, Qian; Peñalver, Pablo; Belmonte Reche, Efres; Andrés Bilbao, María; Lucas Rodríguez, Ricardo; Paz Báñez, María Violante de; Kuipers, Oscar P.; Morales, Juan Carlos; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica; Junta de Andalucía; Dutch Research Council
In the era of antimicrobial resistance, the identification of new compounds with strong antimicrobial activity and the development of alternative therapies to fight drug-resistant bacteria are urgently needed. Here, we have used resveratrol, a safe and well-known plant-derived stilbene with poor antimicrobial properties, as a scaffold to design several new families of antimicrobials by adding different chemical entities at specific positions. We have characterized the mode of action of the most active compounds prepared and have examined their synergistic antibacterial activity in combination with traditional antibiotics. Some alkyl- and silyl-resveratrol derivatives show bactericidal activity against Gram-positive bacteria in the same low micromolar range of traditional antibiotics, with an original mechanism of action that combines membrane permeability activity with ionophore-related activities. No cross-resistance or antagonistic effect was observed with traditional antibiotics. Synergism was observed for some specific general-use antibiotics, such as aminoglycosides and cationic antimicrobial peptide antibiotics. No hemolytic activity was observed at the active concentrations or above, although some low toxicity against an MRC-5 cell line was noted.
Chitosan-based hydrogels obtained via photoinitiated click polymer IPN reaction
(Elsevier, 2023-06) Sánchez Cid, Pablo; Romero García, Alberto; Paz Báñez, María Violante de; Pérez-Puyana, Víctor Manuel; Universidad de Sevilla. Departamento de Ingeniería Química; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica; Universidad de Sevilla. Departamento de Ingeniería Química y Ambiental; Ministerio de Ciencia e Innovación (MICIN). España; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Junta de Andalucía; Universidad de Sevilla. TEP229: Tecnología y Diseño de Productos Multicomponentes; Universidad de Sevilla. FQM135: Carbohidratos y Polímeros
Chitosan (CTS) is a polysaccharide with a wide variety of applications in the biomedical field, owing to its outstanding disinfectant properties, biocompatibility and biodegradability, but with limited mechanical properties. The proposed strategy to improve CTS-based hydrogel properties in this study is the formation of a semi-interpenetrating polymer network (semi-IPN). In this way, a photo-initiated radical click reaction was proposed to obtain a synthetic polymer, whose components were included in a CTS solution, resulting in the semi-IPN network after UV illumination. Different crosslinking degrees (CD) and CTS/polymer ratios were evaluated through rheological characterization, along with an assessment of both variables based on an experimental model design, obtaining that, for every CTS/polymer ratio, intermediate values of CD (8 %) offered the best rheological properties. In addition, chemical and microstructural characterization were carried out for selected hydrogels, obtaining consistent results according to rheological characterization, as the 1/1 CTS/polymer ratio with CD 8 % hydrogel displayed the most homogeneous pore size and distribution, consequently leading to the best rheological performance.
Homochiral imidazolium-based dicarboxylate silver(i) compounds: synthesis, characterisation and antimicrobial properties
(Royal Society of Chemistry, 2022-03) Carrasco Carrasco, Carlos Jesús; Montilla Ramos, Francisco Javier; Álvarez González, Eleuterio; Galindo del Pozo, Agustín; Pérez Aranda, María; Pajuelo Domínguez, Eloísa; Alcudia Cruz, Ana; Universidad de Sevilla. Departamento de Química Inorgánica; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica; Universidad de Sevilla. Departamento de Microbiología y Parasitología; Ministerio de Ciencia, Innovación y Universidades (MICINN). España; Junta de Andalucía
Complexes [Ag(LR)], 2 (LR = 2,2′-(imidazolium-1,3-diyl)di(2-alkylacetate)), were prepared by treatment of compounds HLR, 1, with Ag2O. They were characterised by analytical, spectroscopic (IR, 1H and 13C NMR and polarimetry) and X-ray methods (2c, 2c′ and 2e). In the solid state, these compounds are novel one-dimensional or two-dimensional coordination polymers in which silver(I) cations are connected via the chiral [LR]− anion with unprecedented coordination modes. The antimicrobial properties of these complexes were evaluated. 2a and 2b′ showed the best antimicrobial properties (minimal inhibitory concentrations and minimal bactericidal concentration) for Pseudomonas aeruginosa and Escherichia coli pathogens. Eutomers 2b′ and 2c′ showed slightly better antimicrobial properties than their respective enantiomers 2b and 2c.
Experimental model design: exploration and optimization of customized polymerization conditions for the preparation of targeted smart materials by the Diels Alder click reaction
(Royal Society of Chemistry, 2019) Iglesias Blanco, Nieves; Galbis Fuster, Elsa; Romero Azogil, Lucía; Benito Hernández, Elena María; Díaz Blanco, Manuel Jesús; García Martín, María de Gracia; Paz Báñez, María Violante de; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica; Ministerio de Economía y Competitividad (MINECO). España; Junta de Andalucía
The experimental model design proposed herein has proved to be an indispensable tool to rapidly and easily elucidate the optimal polymerization conditions in the preparation of tailor-made responsive materials for biomedical applications. The use of reversible covalent bonds for the synthesis of new materials provides the polymer structures with novel functionalities and applications. The Diels–Alder (DA) reaction is an ideal synthetic method for the preparation of functional and responsive biomaterials under mild and undemanding conditions. The present work details the optimization of the polymerization conditions to synthesize two families of thermo-sensitive polymers, with either reduction-responsive properties or enhanced hydrophilicity. These polymers have been successfully prepared from two functional bisdiene monomers: a difurfuryl dithiodiethanol derivative (DiT-Fur, 1) and a difurfuryl-dithiothreitol derivative (DTT-Fur, 2), respectively, using the same bismaleimide (DMDOO, 3) derived from triethylene glycol in both systems. Twenty experiments were conducted and a Box–Behnken experimental design was used to evaluate the importance of temperature and the water content in terms of the polymer molecular weights (Mn, determined by 1H NMR). In addition, the progress of the polymerizations at selected times was accurately monitored via IR spectroscopy. Higher temperatures were discarded since previous thermo-lability studies demonstrated that the retro-DA reaction could occur at temperatures as low as 50 °C. Temperature proved to be the most influential variable in the final Mn, exerting opposite effects in both systems. We envision that this experimental approach, applied to other polymerization processes, can enlighten the influence of key parameters in the final product obtained.
Design and manufacturing by fused filament technique of novel YSZ porous grafts infiltrated with PCL/PVA/AgNPs for large bone defects repairing
(Elsevier, 2024-02-19) Herranz, Gemma; Hidalgo, Javier; Axelrad, Victoria; Delgado-Pujol, Ernesto J.; Berges, Cristina; Naranjo, Juan Alfonso; Pinilla, Juan; Begines Ruiz, Belén; Alcudia Cruz, Ana; Torres Hernández, Yadir; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica; Universidad de Sevilla. Departamento de Ingeniería y Ciencia de los Materiales y del Transporte; Ministerio de Ciencia e Innovación (MICIN). España; European Union (UE); Junta de Castilla-La Mancha
Addressing large bone segmental defects remains a profound challenge in orthopaedic surgery, demanding graft designs that mirror patient-specific defects while ensuring vascularization, osteoconduction, and structural integrity. Conventional approaches fall short in achieving this level of customization and functionality. This work leverages fuse filament fabrication (FFF) to fabricate innovative yttria stabilize zirconia graft designs that combine several strategies to tackle these multifaceted challenges. Graft designs ingeniously incorporate dense and porous structures mimicking the intricate architecture of natural bone for improved structural integrity and different ridges and protrusions to enhance the fixation. Additionally, these grafts undergo infiltration with PCL/PVA/AgNPs composite polymers, enriching biocompatibility, structural integrity, and antibacterial properties, fostering conducive conditions for optimal bone growth. Attaining printable filaments with YSZ powders below 50 nm and loads reaching 50 vol% marks a pioneering advancement in bone graft fabrication via Fused Filament Fabrication (FFF). This enabled high densification and low grain size at reduced sintering temperatures, imperative to achieve high mechanical performance. The biodegradation capacity of biopolymers in PBS and their role in the mechanical behaviour of grafts have been assessed, demonstrating the beneficial potential of the multicomponent graft proposed reaching strength values of 90–105 MPa.
Biodegradable double cross-linked chitosan hydrogels for drug delivery: Impact of chemistry on rheological and pharmacological performance
(Elsevier, 2020-12) Iglesias Blanco, Nieves; Galbis Fuster, Elsa; Valencia, Concepción; Díaz Blanco, Manuel Jesús; Lacroix, Bertrand; Paz Báñez, María Violante de; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica; Ministerio de Ciencia, Innovación y Universidades (MICINN). España; Junta de Andalucía
This study investigates the impact of dual ionic and covalent cross-links (ion-XrL and cov-XrL) on the properties of chitosan-based (CTS) hydrogels as eco-friendly drug delivery systems (DDS) for the model drug diclofenac sodium (DCNa). Citric acid and a diiodo-trehalose derivative (ITrh) were the chosen ionic and covalent cross-linker, respectively. The novel hydrogels completely disintegrated within 96 h by means of a hydrolysis process mediated by the enzyme trehalase. As far as the authors are aware, this is the first time that a trehalose derivative has been used as a covalent cross-linker in the formation of biodegradable hydrogels. The impact of CTS concentration and degree of cov-XrL on rheological parameters were examined by means of an experimental model design and marked differences were found between the materials. Hydrogels with maximum elastic properties were achieved at high CTS concentrations and high degrees of cov-XrL. DCNa-loaded formulations displayed well-controlled drug-release profiles strongly dependent on formulation composition (from 17% to 40% in 72 h). Surprisingly, higher degrees of covalent cross-linking led to a boost in drug release. The formulations presented herein provides a simple and straightforward pathway to design fully biodegradable, tailor-made controlled drug delivery systems with improved rheological properties.
Metabolites and tissue distribution of resveratrol in the pig
(Wiley-Blackwell, 2011-08) Azorín-Ortuño, María; Yáñez-Gascón, María J.; Vallejo, Fernando; Pallarés, Francisco J.; Larrosa, Mar; Lucas Rodríguez, Ricardo; Morales, Juan C.; Tomás-Barberán, Francisco A.; García-Conesa, María T.; Espín, Juan C.; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica; Ministerio de Ciencia e Innovación (MICIN). España; Comunidad Autónoma de Murcia
Scope: trans-Resveratrol (RES) and/(or) its metabolites exert many effects in vivo. Our aim was to study the metabolism and tissue distribution of RES using the pig, a mammal physiologically close to humans. Methods and results: Forty-seven tissues, organs and fluids were analyzed 6h after intragastric RES administration (5.9mg/kg body weight) using HPLC-MS/MS. Twelve RES and seven dihydroresveratrol (DH-RES) metabolites were detected. DH-RES was the main metabolite in cecum, colon and rectum, whereas RES-3-O-glucuronide was the most abundant one in fluids and organs. Approximately 74.5% of the total RES administered was recovered in the form of RES, DH-RES and derived metabolites (65.1% along the gastrointestinal tract, 7.7% in urine, 1.2% in bile and 0.5% in organs). We report here, for the first time, the occurrence of RES ribosyl-sulfate derivative, DH-RES diglucuronide, DH-RES sulfoglucuronide and DH-RES disulfate as well as the metabolic profile of RES and DH-RES in the aorta, lymph, lymph node, ovaries, uterus, cerebellum, pancreas, urinary bladder tissue, fat and muscle. Conclusion: This study contributes to the clarification of the metabolism and tissue distribution of RES and could help to further understand the mechanisms underlying its effects.
Chiral sulfur derivatives in the allylation of acyl hydrazones: C 2-symmetric bis-sulfinamides as enhanced chiral organic promoters
(Royal Society of Chemistry, 2010-10) Fernández Fernández, Inmaculada; Alcudia Cruz, Ana; Gori, Beatrice; Valdivia Giménez, Victoria Esther; Recio Jiménez, Rocío; García, María Victoria; Khiar, Noureddine; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica; Dirección General de Investigación Científica y Técnica (DGICYT). España; Junta de Andalucía
Monosulfinamides and C2-symmetric bis-sulfinamides are convenient neutral chiral promoters in the allylation of acyl hydrazones, the nature of the spacer and the substituent at the sulfinyl sulfur are key elements for the enantioselectivity of the process.
DMAP-Catalysed Sulfinylation of Diacetone-D-Glucose: Improved Method for the Synthesis of Enantiopure tert-Butyl Sulfoxides and tert-Butanesulfinamide
(Wiley Online Library, 2014-11) Chelouan, Ahmed; Recio Jiménez, Rocío; Alcudia Cruz, Ana; Khiar, Noureddine; Fernández Fernández, Inmaculada; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica; Ministerio de Economía y Competitividad (MINECO). España; Junta de Andalucía
An improved method for the tert-butanesulfinylation of diacetone glucose with tert-butanesulfinyl chloride is reported. The method is based on a beneficial effect of catalytic DMAP, which enhances both the rate of the reaction and the enantioselectivity of the process to give (R S)-diastereomer 2 R S with a 94 % de and in quantitative yield. (R S)-DAG sulfinate ester 2 R S is an excellent intermediate for the synthesis of enantiopure tert-butyl sulfoxides. Grignard agents and organolithium reagents can displace smoothly the diacetone glucose moiety to give synthetically relevant enantiopure sulfoxides, including highly functionalized derivatives, in high yields and with high enantioselectivities. (R S)-DAG sulfinate ester 2 R S is also an excellent N-sulfinylating agent; simple addition of LiHMDS (lithium hexamethyldisilazide) in THF gives (S S)-tert-butanesulfinamide, and N-tert-butanesulfinylimines are then formed in a two-step one-pot manner. N-Alkylated tert-butanesulfinamides are formed by the condensation of 2 R S with lithium amides. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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