Artículos (Instituto de Investigaciones Químicas (IIQ) – CIC Cartuja)

URI permanente para esta colecciónhttps://hdl.handle.net/11441/10959

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β-Cyclodextrin-based geometrically frustrated amphiphiles as one-component, cell-specific and organ-specific nucleic acid delivery systems
(Elsevier, 2025-01-01) Rivero Barbarroja, Gonzalo; López Fernández, José; Juárez Gonzálvez, Inmaculada; Fernández Clavero, C.; Di Giorgio, Christophe; Vélaz, Itziar; Ortiz Mellet, Carmen; García Fernández, José M.; Universidad de Sevilla. Departamento de Química Orgánica; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Agencia Estatal de Investigación. España; European Union (UE)
We introduce an innovative β-cyclodextrin (βCD)-prototype for delivering nucleic acids: “geometrically frustrated amphiphiles (GFAs).” GFAs are designed with cationic centers evenly distributed across the primary O6 and secondary O2 positions of the βCD scaffold, while hydrophobic tails are anchored at the seven O3 positions. Such distribution of functional elements differs from Janus-type architectures and enlarges the capacity for accessing strictly monodisperse variants. Changes at the molecular level can then be correlated with preferred self-assembly and plasmid DNA (pDNA) co-assembly behaviors. Specifically, GFAs undergo pH-dependent transition between bilayered to monolayered vesicles or individual molecules. GFA-pDNA nanocomplexes exhibit topological and internal order characteristics that are also a function of the GFA molecular architecture. Notably, adjusting the pKa of the cationic heads and the hydrophilic-hydrophobic balance, pupa-like arrangements implying axial alignments of GFA units flanked by quasi-parallel pDNA segments are preferred. In vitro cell transfection studies revealed remarkable differences in relative performances, which corresponded to distinct organ targeting outcomes in vivo. This allowed for preferential delivery to the liver and lung, kidney or spleen. The results collectively highlight cyclodextrin-based GFAs as a promising class of molecular vectors capable of finely tuning cell and organ transfection selectivity
STD NMR Epitope Perturbation by Mutation Unveils the Mechanismof YM155 as an Arginine-Glycosyltransferases Inhibitor Effective inTreating Enteropathogenic Diseases
(American Chemical Society, 2025-03) Ramírez Cárdenas, Jonathan; Taleb, Víctor; Calvaresi, Valeria; Struwe, WB; El Qaidi, Samir; Zhu, Congrui; Muñoz García, Juan Carlos; Angulo Álvarez, Jesús; Universidad de Sevilla. Departamento de Química Orgánica; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Agencia Estatal de Investigación. España; European Union (UE); Gobierno de Aragón
Enteropathogenic arginine-glycosyltransferases(Arg-GTs) alter higher eukaryotic proteins by attaching a GlcNAcresidue to arginine acceptor sites, disrupting essential pathwayssuch as NF-κB signaling, which promotes bacterial survival. Theseenzymes are potential drug targets for treating related diseases. Inthis study, we present a novel STD NMR Epitope Perturbation byMutation spectroscopic approach that, in combination withhydrogen−deuterium exchange mass spectrometry (HDX-MS),and molecular dynamics simulations, shows that the highly potentbroad-spectrum anticancer drug YM155 serves as a potentialnoncompetitive inhibitor of these enzymes. It induces aconformation of the arginine acceptor site unfavorable for GlcNActransfer, which underlies the molecular mechanism by which thiscompound exerts its inhibitory function. Finally, we also demonstrate that YM155 effectively treats enteropathogenic diseases in amouse model, highlighting its therapeutic potential. Overall, our data suggest that this compound can be repurposed to not only treatcancer but also infectious diseases.
Light-controlled assembly and disassembly of cyclodextrin-bisazobenzene supramolecular complexes
(Elsevier, 2025-04-16) Fernández Clavero, Carlos; Rivero Barbarroja, Gonzalo; Carmona, Thais; García Iriepa, C.; Marcelo, Gema; Tros de Ilarduya, Conchita; Ortiz Mellet, Carmen; García Fernández, José M.; Benito, Juan M.; Mendicuti, Francisco; Universidad de Sevilla. Departamento de Química Orgánica; Ministerio de Ciencia, Innovación y Universidades (MICINN). España; Agencia Estatal de Investigación. España; European Union (UE); Universidad de Alcalá
The inclusion complexation of a water soluble bis-azobenzene derivative (bis-Azo) and its monotopic analog (mono-Azo) with α-, β-, and γ-cyclodextrins (CyDs) was investigated as a prototype for light-responsive selfassembling systems. Using spectroscopic techniques (UV–vis, induced circular dichroism, 1 H NMR), computational methods (molecular mechanics and dynamics), and thermodynamic analyses, we examined the photoswitching properties, stability, and structural dynamics of these systems. The azobenzene moieties in the Eisomer of mono-Azo and bis-Azo consistently showed strong affinity for the αCyD cavity, characterized by high association constants. In contrast, no complex formation was observed upon photoinduced E-to-Z isomerization. For bis-Azo, this implies the formation of supramolecular αCyD dimers, with the spatial separation between the oppositely oriented host components determined by the connector linking the two azobenzene moieties in the Econfigured ditopic guest. This complex disassembles upon photoswitching, driven by the structural disruption associated with the Z-form. Both the E-and Z-isomers fitted in the cavity of βCyD, with moderate selectivity towards the E-form. A similar scenario was found for complexes with γCyD when using low concentrations of the host. Interestingly, at high concentrations γCyD formed low-solubility pseudopolyrotaxane-type supramolecular architectures with bis-Azo, which were disrupted upon Z-isomer photoisomerization. All the complexes demonstrated high fatigue resistance, maintaining structural integrity after multiple isomerization cycles. This work advances the design of stimuli-responsive preorganized supramolecular systems, with potential applications in nucleic acid delivery through dual pH/light-sensitive mechanisms.
The two yeast cytochrome c isoforms differentially regulate supercomplex assembly and mitochondrial electron flow
(Elsevier, 2025-06) Guerra Castellano, Alejandra; Aneas, Manuel; Tamargo Azpilicueta, Joaquín; Márquez Escudero, Inmaculada; Olloqui Sariego, José Luis; Calvente Pacheco, Juan José; Rosa Acosta, Miguel Ángel de la; Díaz Moreno, Irene; Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular; Universidad de Sevilla. Departamento de Química Física; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Junta de Andalucía
Mitochondria play a crucial role in cellular energy production, signaling and homeostasis. Respiratory supercomplexes represent evolutionary well-conserved, stable associations between membrane complexes and molecules, including proteins and lipids, within the inner mitochondrial membrane. They dynamically respond to metabolic demands and enhance the electron transfer rate, thereby reducing the production of ROS. Recent research has unveiled cytochrome c, a mobile electron carrier between complexes III and IV, as a potential key player in orchestrating the formation of these supra-associations. This study centers on elucidating the role of cytochrome c in modulating the assembly of supercomplexes, using the Saccharomyces cerevisiae yeast as a model system for mitochondrial metabolism. BN-PAGE and mass spectrometry-based proteomic analysis were employed to examine supercomplex organization in yeast strains expressing different cytochrome c isoforms, grown under fermentative and respiratory conditions. Our results demonstrate that both isoforms of cytochrome c contribute to supercomplex assembly, with isoform-2 significantly improving electron transfer and lowering ROS levels. We propose a model in which cytochrome c acts as a scaffold for the recruitment of assembly factors, facilitating the formation of higher order supercomplexes such as III2IV2. This model highlights cytochrome c's role beyond electron transfer, as it regulates supercomplex assembly and mitochondrial homeostasis.
Pathways to Metal-Ligand Cooperation in Quinoline-Based Titanium(IV) Pincers: Nonelectrophilic N-methylation, Deprotonation, and Dihydropyridine Formation
(American Chemical Society, 2021-06-07) Fandos, Rosa; Rodríguez Delgado, Antonio; Rodríguez, Ana; Romero, Iván; Organero, Juan Ángel; Álvarez González, Eleuterio; Universidad de Sevilla. Departamento de Química Inorgánica; Junta de Castilla-La Mancha; Ministerio de Economía y Competitividad (MINECO). España
A series of titanium(IV) complexes stabilized by quinoline-based pincer ligands have been synthesized and characterized. The reaction of [TiCp*Me3] with 8-hydroxy-2-quinolinecarboxaldehyde results in [TiCp*Me{κ3-N,O,O-(OCH)(8-O-N-Me-quin)}] (1), which shows an uncommon N-methylation/dearomatization of the pyridinic ring; in contrast, when 8-hydroxy-2-quinolinemethanol reacts with the same Ti(IV) trimethyl derivative, the expected monoalkyl complex [TiCp*Me{κ3-N,O,O-(OCH2)(8-O-quin)}] (2) is formed. The pincer ligand in 2 can be dearomatized by deprotonation of the methylene fragment, yielding [TiCp*Me{κ3-N,O,O-(OCH)(8-O-quin)}][Li(Et2O)] (3·Et2O) and [TiCp*Me{k3-N,O,O-(OCH)(8-O-quin)}][Li(Py)2] (3·2Py), or by incorporation of a hydride group into the para position of the pyridinic ring, giving [TiCp*Me{κ3-N,O,O-(OCH2)(4-H-8-O-quin)}][Li·THF] (5). Compounds 1, [TiCp*{κ3-N,O,O-(OCH2)(4-H-8-O-quin)}]2 (6), and [TiCp*{κ3-N,O,O-(OCH2)(4-H-8-O-quin)}]2[Li·THF]2(μ-O)] (7) have been studied by X-ray diffraction. Additionally, DFT quantum mechanical calculations were performed on complexes 1 and 2.
Sweet MOFs: exploring the potential and restraints of integrating carbohydrates with metal-organic frameworks for biomedical applications
(Royal Soc Chemistry, 2025-03-04) Zuliani, A; Ramos, V.; Escudero Belmonte, Alberto; Khiar, Noureddine; Universidad de Sevilla. Departamento de Química Inorgánica; Junta de Andalucía; Ministerio de Ciencia e Innovación (MICIN). España; European Union (UE)
The unique features of metal–organic frameworks (MOFs) such as biodegradability, reduced toxicity and high surface area offer the possibility of developing smart nanosystems for biomedical applications through the simultaneous functionalization of their structure with biologically relevant ligands and the loading of biologically active cargos, ranging from small drugs to large biomacromolecules, into their pores. Aiming to develop efficient, naturally inspired biocompatible systems, recent research has combined organic and materials chemistry to design innovative composites that exploit carbohydrate chemistry for the functionalization and structural modification of MOFs. Scientific investigation in the field has seen a significant rise in the past five years, and it is becoming crucial to acknowledge both the limits and benefits of this approach for future investigation. In this review, the latest research results merging carbohydrates and MOFs are discussed, with a particular emphasis on the advances in the field and the remaining challenges, including addressing sustainability and real-case applicability.
Fluorinated Man9 as a High Mannose Mimetic to Unravel Its Recognition by DC-SIGN Using NMR
(American Chemical Society, 2023-11-08) Silva Díaz, Adrián; Ramírez Cárdenas, Jonathan; Muñoz García, Juan Carlos; de la Fuente, M. Carmen; Thépaut, Michel; Fieschi, Franck; Ramos Soriano, Javier; Angulo Álvarez, Jesús; Rojo, Javier; Universidad de Sevilla. Departamento de Química Orgánica; Ministerio de Ciencia e Innovación (MICIN). España; Agencia Estatal de Investigación. España; European Union (UE)
Lectins are capable of reading out the structural information contained in carbohydrates through specific recognition processes. Determining the binding epitope of the sugar is fundamental to understanding this recognition event. Nuclear magnetic resonance (NMR) is a powerful tool to obtain this structural information in solution; however, when the sugar involved is a complex oligosaccharide, such as high mannose, the signal overlap found in the NMR spectra precludes an accurate analysis of the interaction. The introduction of tags into these complex oligosaccharides could overcome these problems and facilitate NMR studies. Here, we show the preparation of the Man9 of high mannose with some fluorine tags and the study of the interaction with its receptor, dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN). This fluorinated ligand has allowed us to apply heteronuclear two-dimensional (2D) 1H,19F STD-TOCSYreF NMR experiments, using the initial slope approach, which has facilitated the analysis of the Man9/DC-SIGN interaction, unequivocally providing the binding epitope.
Rational Design of Dual-Domain Binding Inhibitors for N-Acetylgalactosamine Transferase 2 with Improved Selectivity over the T1 and T3 Isoforms
(American Chemical Society, 2024-09-11) Compañón, Ismael; Ballard, Collin J.; Lira Navarrete, Enardi; Santos, Tanausú; Monaco, Serena; Muñoz García, Juan Carlos; Angulo Álvarez, Jesús; Ghirardello, Mattía; Universidad de Sevilla. Departamento de Química Orgánica; Agencia Estatal de Investigación. España; Universidad de La Rioja; Gobierno de Aragón; European Union (UE)
The GalNAc-transferase (GalNAc-T) family, consisting of 20 isoenzymes, regulates the O-glycosylation process of mucin glycopeptides by transferring GalNAc units to serine/threonine residues. Dysregulation of specific GalNAc-Ts is associated with various diseases, making these enzymes attractive targets for drug development. The development of inhibitors is key to understanding the implications of GalNAc-Ts in human diseases. However, developing selective inhibitors for individual GalNAc-Ts represents a major challenge due to shared structural similarities among the isoenzymes and some degree of redundancy among the natural substrates. Herein, we report the development of a GalNAc-T2 inhibitor with higher potency compared to those of the T1 and T3 isoforms. The most promising candidate features bivalent GalNAc and thiophene moieties on a peptide chain, enabling binding to both the lectin and catalytic domains of the enzyme. The binding mode was confirmed by competitive saturation transfer difference NMR experiments and validated through molecular dynamics simulations. The inhibitor demonstrated an IC50 of 21.4 μM for GalNAc-T2, with 8- and 32-fold higher selectivity over the T3 and T1 isoforms, respectively, representing a significant step forward in the synthesis of specific GalNAc-T inhibitors tailored to the unique structural features of the targeted isoform.
Fluorinated trehalose analogues for cell surface engineering and imaging of Mycobacterium tuberculosis
(2024-08-12) Guy, Collette S.; Gott, James A.; Ramírez Cárdenas, Jonathan; de Wolf, Cristopher; Furze, Christopher M.; West, Geoff; Muñoz García, Juan Carlos; Angulo Álvarez, Jesús; Fullam, Elizabeth; Universidad de Sevilla. Departamento de Química Orgánica; Ministerio de Ciencia e Innovación (MICIN). España; Agencia Estatal de Investigación. España; European Union (UE)
The sensitive, rapid and accurate diagnosis of Mycobacterium tuberculosis (Mtb) infection is a central challenge in controlling the global tuberculosis (TB) pandemic. Yet the detection of mycobacteria is often made difficult by the low sensitivity of current diagnostic tools, with over 3.6 million TB cases missed each year. To overcome these limitations there is an urgent need for next-generation TB diagnostic technologies. Here we report the use of a discrete panel of native 19F-trehalose (F-Tre) analogues to label and directly visualise Mtb by exploiting the uptake of fluorine-modified trehalose analogues via the mycobacterial trehalose LpqY-SugABC ATP-binding cassette (ABC) importer. We discovered the extent of modified F-Tre uptake correlates with LpqY substrate recognition and characterisation of the interacting sites by saturation transfer difference NMR coupled with molecular dynamics provides a unique glimpse into the molecular basis of fluorine-modified trehalose import in Mtb. Lipid profiling demonstrated that F-Tre analogues modified at positions 2, 3 and 6 are incorporated into mycobacterial cell-surface trehalose-containing glycolipids. This rapid one-step labelling approach facilitates the direct visualisation of F-Tre-labelled Mtb by Focused Ion Beam (FIB) Secondary Ion Mass Spectrometry (SIMS), enabling detection of the Mtb pathogen. Collectively, our findings highlight that F-Tre analogues have potential as tools to probe and unravel Mtb biology and can be exploited to detect and image TB.
Fast Quantitative Validation of 3D Models of Low-Affinity Protein-Ligand Complexes by STD NMR Spectroscopy
(American Chemical Society, 2024-06-07) Nepravishta, Ridvan; Ramírez Cárdenas, Jonathan; Rocha, Gabriel; Walpole, Samuel; Hicks, Thomas; Monaco, Serena; Muñoz García, Juan Carlos; Angulo Álvarez, Jesús; Universidad de Sevilla. Departamento de Química Orgánica; Biotechnology and Biological Sciences Research Council (BBSRC). U. K.; Agencia Estatal de Investigación. España; Ministerio de Ciencia e Innovación (MICIN). España; European Union (UE)
Low-affinity protein–ligand interactions are important for many biological processes, including cell communication, signal transduction, and immune responses. Structural characterization of these complexes is also critical for the development of new drugs through fragment-based drug discovery (FBDD), but it is challenging due to the low affinity of fragments for the binding site. Saturation transfer difference (STD) NMR spectroscopy has revolutionized the study of low-affinity receptor–ligand interactions enabling binding detection and structural characterization. Comparison of relaxation and exchange matrix calculations with 1H STD NMR experimental data is essential for the validation of 3D structures of protein–ligand complexes. In this work, we present a new approach based on the calculation of a reduced relaxation matrix, in combination with funnel metadynamics MD simulations, that allows a very fast generation of experimentally STD-NMR-validated 3D structures of low-affinity protein–ligand complexes.
Differential Solvent DEEP-STD NMR and MD Simulations Enable the Determinants of the Molecular Recognition of Heparin Oligosaccharides by Antithrombin to Be Disentangled
(MDPI, 2024-04-26) Parafioriti, Michela; Elli, Stefano; Muñoz García, Juan Carlos; Ramírez Cárdenas, Jonathan; Yates, Edwin A.; Angulo Álvarez, Jesús; Guerrini, Marco; Universidad de Sevilla. Departamento de Química Orgánica; Fundación G. Ronzoni. Italia; Ministerio de Ciencia e Innovación (MICIN). España; Agencia Estatal de Investigación. España; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER)
The interaction of heparin with antithrombin (AT) involves a specific sequence corresponding to the pentasaccharide GlcNAc/NS6S-GlcA-GlcNS3S6S-IdoA2S-GlcNS6S (AGA*IA). Recent studies have revealed that two AGA*IA-containing hexasaccharides, which differ in the sulfation degree of the iduronic acid unit, exhibit similar binding to AT, albeit with different affinities. However, the lack of experimental data concerning the molecular contacts between these ligands and the amino acids within the protein-binding site prevents a detailed description of the complexes. Differential epitope mapping (DEEP)-STD NMR, in combination with MD simulations, enables the experimental observation and comparison of two heparin pentasaccharides interacting with AT, revealing slightly different bound orientations and distinct affinities of both glycans for AT. We demonstrate the effectiveness of the differential solvent DEEP-STD NMR approach in determining the presence of polar residues in the recognition sites of glycosaminoglycan-binding proteins.
Organocatalytic Applications of Sulfonyl Squaramides in Anion-Recognition Strategies
(Willey, 2024-10-16) Benítez Narváez, Manuel; Matador Martínez, Esteban; Velázquez Muñoz, Marta; Lassaletta, José M.; Fernández Fernández, Rosario Fátima; Monge Fernández, David; Universidad de Sevilla. Departamento de Química Orgánica; Ministerio de Ciencia e Innovación (MICIN). España; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Junta de Andalucía
A modular, 3-steps protocol for the synthesis of N-sulfonyl squaramides has been developed. The strategic installation of a tetrahedral, electron-withdrawing sulfonyl group into the squaramido core allowed the prevention of undesired self-aggregations, therefore upgrading the solubility in common organic solvents, and moreover, enhancing their H-bond donor abilities for molecular recognition. These unique features have been efficiently exploited in two different ion-pairing reactions: (i) the challenging C4-selective dearomatization of 2-picoline with silyl ketene acetals and (ii) the tritylation of N-methylindole. Furthermore, their catalytic activities have been directly compared with other common and well-established (thio)urea analogues and related H-bond donors, revealing that highly acidic designs are essential to reach optimal catalytic performances.
Ni‐Catalyzed (2+2+2) Cycloaddition of Alkynes to Form Arenes and Pyridines at Low Catalyst Loadings
(Willey, 2024-10-09) Martín García, María Trinidad; Maya Díaz, Celia María; Galindo del Pozo, Agustín; Nicasio Jaramillo, María del Carmen; Universidad de Sevilla. Departamento de Química Inorgánica; Ministerio de Ciencia e Innovación (MICIN). España; Agencia Estatal de Investigación. España
We report the Ni-catalyzed cyclotrimerization of terminal alkynes at very low loadings of catalysts (0.05 mol% for all substrates). The nickel catalyst containing a terphenyl phosphine ligand allows carrying out the reactions at room temperature in only 30 min, providing the arene products as a single regioisomer in most cases. The Ni complex is also competent for the synthesis of polysubstituted pyridines through the cycloadditions of diynes and nitriles at mild temperatures (25 ° or 50 °C) and low Ni loadings (1 mol%). Experimental data and computational studies support the involvement of monoligated PNi species in all fundamental steps of the catalytic cycle.
A Sustainable Lecithin-based Ligand for the Bio-functionalization of Iron and Hybrid Metal Organic Frameworks (MOFs) Nanoparticles with the Sugar Mannose
(Royal Society of Chemistry, 2024) Cova, Camilla María; Ramos, V.; Escudero Belmonte, Alberto; Holgado, J. P.; Khiar, N.; Zuliani, A.; Universidad de Sevilla. Departamento de Química Inorgánica; Junta de Andalucía; Ministerio de Ciencia e Innovación (MICIN). España; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); European Cooperation in Science and Technology (COST)
The functionalization of nanoparticles with specific ligands, such as antibodies, peptides, and small molecules, plays a critical role in achieving targeted delivery, enhancing biocompatibility, and controlling drug release. However, to date, practically no attention has been paid to the design of green ligands. Herein, an innovative approach to develop a sustainable ligand for nanoparticle functionalization is reported. Its synthesis involved a photochemical thio-ene “click” reaction between the natural compounds phosphatidylcoline, the main component of lecithin, and cysteine, followed by a reductive amination with mannose, a sugar of growing interest for biomedical targeting, in a continuous flow hydrogenation reactor. Comprehensive characterization techniques, including nuclear magnetic resonance (NMR), mass spectrometry (MS), Fourier-transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and elemental analysis, confirmed the structure and properties of the novel ligand. The environmental sustainability of the ligand was evaluated determining some green metrics using the EATOS software. The obtained E-factor was compared with a conventional PEG-based ligand. The newly developed lecithin-derived ligand was successfully used to functionalize diverse NP platforms, including the MOFs MIL-101(Fe), PCN-222, UiO-66, and iron nanoparticles (in the form of akaganeite), demonstrating its potential in nanomedicine applications.
Synthesis, Characterization, and Preliminary In Vitro Anticancer Activity of Zinc Complexes Containing Amino Acid-Derived Imidazolium-Based Dicarboxylate Ligands
(Multidisciplinary Digital Publishing Institute (MDPI), 2025-03-30) Carrasco Carrasco, Carlos Jesús; Pastor Navarro, Antonio; Conejo Argandoña, María del Mar; Álvarez González, Eleuterio; Calderón Montaño, José Manuel; López Lázaro, Miguel; Galindo del Pozo, Agustín; Universidad de Sevilla. Departamento de Química Inorgánica; Universidad de Sevilla. Departamento de Farmacología; Ministerio de Ciencia e Innovación (MICIN). España
Coordination polymers containing zinc and imidazolium-based dicarboxylate ligands, [LR]−, were synthesized by reacting zinc acetate with HLR compounds, 1. The resulting complexes were characterized and structurally identified using single-crystal X-ray diffraction, revealing polymeric structures for the complexes [Zn(LR)2]n (R = Gly, 2a; βAla, 2b) and [Zn(LLeu)2(H2O)2]n (2c). In these structures, the [LR]− ligands adopt a bridging monodentate μ-κ1-O1,κ1-O3 coordination mode, resulting in distorted tetrahedral (2a, 2b) or octahedral (2c) geometries around the zinc center. When the synthesis was carried out in the presence of amino acids, mixed ligand complexes [Zn(LR)(aa)(H2O)]n (R = aa = Val, 2d, and R = aa = Ile, 2e) were formed. Complexes 2d–2e were also structurally characterized using single-crystal X-ray crystallography, revealing that the ligand [LR]− maintained the same coordination mode, while the zinc center adopted a five-coordinated geometry. The cytotoxic activity of complexes 2a–2e was evaluated against three cancer cell lines and one non-cancerous cell line. Remarkably, these complexes exhibited higher toxicity against cancer cells than against the non-cancerous cell line, and they showed greater selectivity than carboplatin, a commonly used chemotherapy drug. Although, in general, these complexes did not surpass the selectivity of gemcitabine, complex 2c stood out for exhibiting a selectivity index value similar to that of gemcitabine against melanoma cells. Among the series, compounds 2a–2c demonstrated the highest activity, with 2a being the only complex with some selective activity against lung cancer. Complex 2b was the most active, though with low selectivity, while complex 2c exhibited the highest selectivity for melanoma and bladder cancer (selectivity index of 3.0).
A machine learning-based nuclear magnetic resonance profiling model to authenticate ’Jerez-Xérès-Sherry’ wines
(Elsevier, 2025-03-26) Hiniesta Valero, Jaime; Guerra Castellano, Alejandra; Fernández Veloso, Andrea; Rosa Acosta, Miguel Ángel de la; Díaz Moreno, Irene; Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular
Traditionally, wine quality and certification have been assessed through sensory analysis by trained tasters. However, this method has the limitation of relying on highly specialized individuals who are typically trained to evaluate only specific types of products, such as those associated with a particular Denomination of Origin (D.O.), etc. While tasters can often identify instances of fraud, they are generally unable to pinpoint its origins or explain the mechanisms behind it. On the other hand, classical biochemistry has made significant progress in understanding various aspects of winemaking. However, it has yet to identify the specific metabolites responsible for the unique characteristics of wines, particularly those influenced by complex variables involving multiple compounds, such as geographical differences between regions or vineyards. The concept of the “Terroir fingerprint” has emerged as a novel approach to wine certification. The concept refers to the unique characteristics imparted to a wine by its geography, climate, and aging process. Nuclear Magnetic Resonance (NMR) technology plays a pivotal role in establishing this “Terroir fingerprint” because it enables precise identification, quantification, and differentiation of the compounds present in wine. NMR provides a highly reproducible and specific method for certification. This work introduces an innovative project that combines NMR technology with Artificial Intelligence to create a profiling model for certifying the authenticity and quality of ‘Jerez-Xérès-Sherry’ wines.
Cytochrome c prompts the recruitment of its nuclear partners SET/TAF-Iβ and NPM1 into biomolecular condensates
(Cell Press, 2024-07-02) Casado Combreras, Miguel Ángel; Velázquez Campoy, Adrián; Martinho, Marlène; Belle, Valérie; Rosa Acosta, Miguel Ángel de la; Díaz Moreno, Irene; Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular; Agencia Estatal de Investigación. España; Ministerio de Ciencia e Innovación (MICIN). España; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Junta de Andalucía; Universidad de Sevilla; European Cooperation in Science and Technology (COST); University of California
Compartmentalization of proteins by liquid-liquid phase separation (LLPS) is used by cells to control biochemical reactions spatially and temporally. Among them, the recruitment of proteins to DNA foci and nucleolar trafficking occur by biomolecular condensation. Within this frame, the oncoprotein SET/ TAF-Ib plays a keyrole in bothchromatin remodelingandDNAdamageresponse,asdoesnucleophosmin (NPM1)whichindeedparticipatesinnucleolar ribosome synthesis. Whereasphase separation byNPM1is widelycharacterized,little is known aboutthatundergonebySET/TAF-Ib.Here,weshowthatSET/TAF-Ib experiences phase separation together with respiratory cytochrome c (Cc), which translocates to the nucleus upon DNA damage. Here we report the molecular mechanisms governing Cc-induced phase separation of SET/TAF-IbandNPM1,wheretwolysine-richclustersofCcareessentialtorecognizemolecular surfaces on both partners in a specific and coordinated manner. Cc thus emerges as a small, globular protein with sequence-encoded heterotypic phase-separation properties
Report on the 23rd FEBS Young Scientists' Forum 2024
(John Wiley & Sons, 2024) Miggiano, Riccardo; Ippolito, Luigi; Paganini, Chiara; Paone, Alessio; Tonelli, Francesca; Trojan, Sonia; Díaz Moreno, Irene; Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular
The 23rd FEBS YSF was held from 26th to 29th June 2024 in Pavia, Italy. Over 100 PhD students and early postdoctoral researchers from around 30 different countries came together at the inspiring rooms of the University of Pavia for a four-day event. This year's topic was ‘Biochemistry for bridging the gap’, meaning the opportunity to have a comprehensive perspective on all biochemistry applications. Four renowned keynote speakers presented their latest research, accompanied by four career-focused speakers, as well as additional sessions on academic career opportunities, including fellowships, women in science, and laboratory sustainability. Additionally, 10 selected YSF participants gave short talks to a large audience, while the remaining attendees shared their research findings through flash talks and two dedicated poster sessions. Scientific exchange and networking were encouraged during the poster sessions, breaks, and the social events. The meeting was a prelude before attending the 48th FEBS congress, celebrated in Milan. The success of the series will be continued during the 24th YSF edition: ‘Inspired by nature, driven by science’, which will take place from 2nd to 5th July 2025 in Sapanca, Türkiye.
Nanosized Porphyrinic Metal–Organic Frameworks for the Construction of Transparent Membranes as a Multiresponsive Optical Gas Sensor
(John Wiley and Sons, 2024) Moscoso, Francisco G.; Romero Guerrero, Juan J.; Rodríguez Lucena, David; Pedrosa, José María; Carrillo Carrión, Carolina; Universidad de Sevilla. Departamento de Química Orgánica; Ministerio de Ciencia e Innovación (MICIN). España; Junta de Andalucía; Consejo Superior de Investigaciones Científicas (CSIC)
The well-known and excellent colorimetric sensing capacity of porphyrins, along with the exceptional structural properties of metal–organic frameworks (MOFs), make porphyrin-based MOFs, such as PCN-222, ideal candidates for the construction of a chemical sensor based on absorbance. However, to the best of authors’ knowledge, no high-quality porphyrin-based MOF gas sensors have been developed to date, most likely due to the difficulties in: 1) preparing nanosized porphyrin-MOFs to minimize scattering in absorbance measurements; and 2) incorporating MOFs into transparent membranes for practical use. Herein, a simple and fast microwave-assisted method for preparing high-quality nanosized PCN-222 crystals and their metalated derivatives PCN-222(M) is reported to finely tune the sensing response. Next, the successful dispersion of these PCN-222(M) nanoparticles into poly(dimethylsiloxane) to create flexible and transparent membranes is demonstrated. This integration yields a multiresponsive optical gas sensor exhibiting excellent sensitivity and the ability to discriminate between various volatile organic compounds via pattern recognition identification.
Exploiting Cross-Responsiveness of Fluorescent Interpenetrated Zirconium–Organic Frameworks Integrated in Polymeric Membranes as a Multi-Analyte Gas Sensor Array
(John Wiley & Sons, 2024) Moscoso, Francisco G.; Rodríguez Lucena, David; Romero Guerrero, Juan J.; Hamad, Said; Carrillo Carrión, Carolina; Pedrosa, José M.; Universidad de Sevilla. Departamento de Química Orgánica; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Junta de Andalucía
In this paper, a series of Zr metal-organic frameworks, whose hexanuclear clusters of Zr are connected with luminescent rodlike dicarboxylic acids, are used for the construction of a sensor array to selectively detect various analyte vapors. The chemical functionalization of the ligand (HOOC[PE-aryl-EP]COOH) (which alternates phenylene(P) and ethynylene(E) units) through the aryl core, is focused on obtaining six Porous Interpenetrated Zirconium-Organic Frameworks (PIZOFs) with distinctive luminescent properties. Particularly, the synthesis of two new ligands (aryl = nitrobenzene;metal-organic frameworks aryl = pyrazine) enabled the preparation of new PIZOFs (UPO-1 and UPO-2) with submicron sizes, thanks to the use of a microwave-assisted synthetic method. The fluorescence properties of these two new PIZOFs, along with four others already reported, are thoroughly evaluated and noticeable changes are observed in their optical properties based on variations in the aryl core of the ligands. Furthermore, the presence of various volatile analyte vapors particularly modified their characteristic emission, resulting in multiple optical responses that are combined to achieve selectivity in detecting these analytes. Specifically, the construction of a fluorescent sensor array is proposed, incorporating the six PIZOFs into polyvinylidene-fluoride (PVDF) films, capable of producing unique identification patterns for each analyte by leveraging the cross-responsiveness of these sensing materials.

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