Artículos (Instituto de Investigaciones Químicas (IIQ) – CIC Cartuja)
URI permanente para esta colecciónhttps://hdl.handle.net/11441/10959
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Artículo El modelo Push-Pull como estrategia de activación y estabilización molecular(Real Sociedad Española de Química, 2025) Corona De Leaniz, Helena; Hidalgo Reinoso, Nereida; Pérez Jiménez, Marina; Cruz Martínez, Felipe de la; Campos Manzano, Jesús; Química InorgánicaEn este trabajo revisamos el concepto de Push-Pull (donador-aceptor) como estrategia para activación de moléculas inertes o para la estabilización de fragmentos altamente reactivos. Este modelo se basa en la combinación de un centro rico y un centro pobre en electrones que, de manera concertada, son capaces de donar (push) y retirar (pull) densidad electrónica de otro fragmento molecular. En esta perspectiva se describen diversos ejemplos que demuestran el interés y aplicabilidad de esta estrategia, incluyendo tanto sistemas que permiten activar moléculas poco reactivas como CO2 o N2, como otros que permiten la estabilización de fragmentos muy reactivos como LiH o LiMe.Artículo Hands-on protocol for preparing water-soluble fractions from agri-food samples for NMR-based metabolomics analysis(Wiley, 2026-04-01) Fernández Veloso, Andrea; Hiniesta Valero, Jaime; Guerra Castellano, Alejandra; Rosa Acosta, Miguel Ángel de la; Díaz Moreno, Irene; Bioquímica Vegetal y Biología Molecular; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Agencia Estatal de Investigación. EspañaThe aim of this study was to address the lack of protocols for nuclear magnetic resonance (NMR)-based metabolomics in the agri-food sector by providing a reproducible workflow for the preparation and analysis of water-soluble metabolite fractions. These fractions, rich in primary metabolites such as sugars, amino acids, and organic acids, are key to assessing agri-food products’ composition, quality, as well as to monitor their manufacturing and development processes. The protocol differentiates solid and liquid matrices, optimizing extraction procedures accordingly. Representative agri-food products—strawberry leaves (solid) and wine (liquid)— were analyzed to demonstrate the method’s versatility and applicability. Key steps include tailored sample preparation, optimization of NMR acquisition, and spectral quality control, ensuring high data quality and reproducibility. The proposed workflow enhances reproducibility across agri-food metabolomics studies and facilitates integration into broader food quality, traceability, and safety frameworks.Artículo Haptotropic Phenomena in Digold(I) Triple-Bonded Complexes(American Chemical Society, 2025-12-05) Nieto Vargas, Ignacio; Cayuela-Castillo, Juan; Fernandez de Cordova, Francisco J.; Fernández, Israel; Ríos Moreno, Pablo; Química Orgánica; Junta de Andalucía; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Agencia Estatal de Investigación. EspañaAddition of either IPrAuOTf or IPrCuOTf (IPr= 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene; OTf = trifluoromethanesulfonate anion) to the digold acetylide IPrAuC≡ CAuIPr results in the selective formation of the corresponding trimetalliccationicspecies[IPrAuC≡C(π-MIPr)AuIPr][OTf](M =AuorCu). Variable-temperature 1H NMRexperiments (VTNMR) reveal that while the homotrimetallic gold complex exhibits dynamic σ,π-exchange insolution at temperaturas even as low as −130°C, the heterometallic analogue presents a static scenario. On the other hand, extensión of the acetylide bridge by one additional acetylide unit using IPrAuC≡C−C≡CAuIPr introduces a new fluxional process in the corresponding analogous trimetallic compounds [IPrAuC≡C(π-MIPr)−C≡CAuIPr][OTf] (M=Auor Cu), namely π,π-exchange. In the case of the copper-containing complex, this Exchange occurs even at low temperatures, whereas Exchange can be thermally arrested in the trigold system at temperaturas below−10°C.Computational studies indicate that the divergent behavior between gold and copper regarding π,π- Exchange does not appear to stem from their interaction with the alkyne fragment but rather in how this interaction changes along the reaction coordinate toward the transition state geometry.Artículo Use of the MOF NU-1000 as a Drug Delivery System for the Antineoplastic Drug Mitoxantrone(MDPI, 2026-05-28) Alfonso, Daniel R.; Moscoso, Francisco G.; Rodríguez Lucena, David; Roales Batanero, Javier; Carrillo Carrión, Carolina; Cascajo Almenara, María Victoria; Santos Ocaña, Carlos; Pedrosa, José M.; Química Orgánica y Farmacéutica; Ministerio de Ciencia e Innovación (MICIN). España; Agencia Estatal de Investigación. España; European Union (UE); Junta de AndalucíaMetal–organic frameworks (MOFs) offer unique opportunities for drug delivery due to their high porosity and the possibility of hosting large drug molecules within well-defined pore systems. In this work, the zirconium-based MOF NU-1000 was investigated as a carrier for the antineoplastic drug mitoxantrone (MTX). NU-1000 particles were synthesized and characterized by PXRD, SEM, and DLS, confirming their crystallinity, morphology, and size distribution. MTX loading was achieved by aqueous incubation and quantified by UV-Vis spectroscopy and thermogravimetric analysis, yielding a high loading capacity of ~40–43 wt%, with most of the uptake occurring within the first three hours. Structural characterization demonstrated that the MOF preserves its crystallinity and morphology after drug incorporation, while the DLS results suggest that MTX is mainly accommodated within the internal pore system. To improve stability under physiological conditions, the composite was coated with NH2-PEG-NH2, resulting in PEG@MTX@NU-1000 particles with enhanced stability in phosphate-buffered saline. Cytotoxicity assays in HeLa cells showed that the PEGylated carrier is largely biocompatible, while PEG@MTX@NU-1000 exhibits a significantly enhanced antiproliferative effect compared to free MTX at short incubation times. These results demonstrate that NU-1000 is a promising platform for MTX delivery, combining high loading capacity, structural stability after PEGylation, and improved short-term therapeutic performance.Artículo Azobenzene-bridged ionizable amphiphilic Janus glycosides for lightcontrolled, single-component and organmodulable pDNA delivery(Nature Research, 2026-02-05) Wang, Zhaoxin; Rivero Barbarroja, Gonzalo; Benito, Juan M.; Maisonneuve, Stéphane; Vélaz, Itziar; Juárez Gonzálvez, Inmaculada; Garrido, María J.; Tros de Ilarduya, Conchita; Ortiz Mellet, Carmen; Xie, Juan; García Fernández, José M.; Química Orgánica; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Agencia Estatal de Investigación. EspañaStimuli-responsive supramolecular systems enable spatiotemporal control of nucleic acid (NA) delivery. To achieve precise and programmable vectors, we designed azobenzene-bridged ionizable amphiphilic Janus glycosides (IAJGs) as single-component, light-responsive DNA carriers. These glucopyranose-based dimers undergo reversible E/Z photoisomerization while forming stable nanocomplexes with plasmid DNA (pDNA). Photoisomerization alters nanocomplex size, surface charge, and internal order, resulting in distinct transfection outcomes. In vitro, O- and S-glycoside derivatives displayed isomer-dependent activity across COS-7, HepG2, and RAW264.7 cells, with pronounced switching effects specially in macrophages. In vivo, systemic administration revealed organ-selective responses:O-glycosides shifted expression from liver to lung upon E→Z conversion, whereas S-glycosides favored spleen targeting. All formulations maintained high cell viability. These results highlight photoswitchable IAJGs as structurally defined vectors for adjustable control over NA delivery and organ tropism.Artículo Broadening the Workflow for Synchrotron-Based X-Ray Fluorescence and X-Ray Absorption Spectroscopy Imaging of Low-Abundance Cellular Metals(Wiley, 2026-03-06) Tamargo Azpilicueta, Joaquín; Giner Arroyo, Rafael Luis; Rivero-García, Pablo; Díaz-Moreno, Sofía; Gómez González, Miguel A; Telfer, Abbey; Campanella, Michelangelo; Rosa Acosta, Miguel Ángel de la; Díaz Moreno, Irene; Bioquímica Vegetal y Biología Molecular; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Agencia Estatal de Investigación. España; Junta de AndalucíaMetals play an essential role in cellular homeostasis and are key components of several formulations currently used in the clinic. Synchrotron-based X-ray microscopy at submicron resolution is a powerful approach to map intracellular elemental distributions and to monitor how these patterns change upon genetic or pharmacological perturbations. However, existing sample-preparation protocols often rely on costly and highly specialized equipment for vitrification and dehydration, limiting their widespread adoption. Here, we present an adapted plunge-freezing and freeze-drying workflow that enables the preparation of mammalian cell samples for X-ray fluorescence (XRF) and X-ray absorption spectroscopy (XAS) studies with submicron resolution in a cost-effective and versatile manner. Furthermore, we define acquisition parameters optimized for the reliable detection of low-abundance metals, such as endogenous iron. We anticipate that this accessible protocol will facilitate the broader implementation of synchrotron-based inner-shell spectromicroscopy in cell biology.
Artículo Bicyclic picomolar OGA inhibitors enable chemoproteomic mapping of its endogenous post-translational modifications(American Chemical Society, 2022-01-05) González Cuesta, Manuel; Sidhu, Peter; Ashmus, Roger A.; Males, Alexandra; Proceviat, Cameron; Madden, Zarina; Rogalski, Jason C.; Busmann, Jill A.; Foster, Leonard J.; García Fernández, José M.; Davies, Gideon J.; Ortiz Mellet, Carmen; Vocadlo, David J.; Química Orgánica; Ministerio de Ciencia e Innovación (MICIN). España; British Columbia Knowledge Development; Canadian Institutes of Health Research (CIHR)Owing to its roles in human health and disease, the modification of nuclear, cytoplasmic, and mitochondrial proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) has emerged as a topic of great interest. Despite the presence of O-GlcNAc on hundreds of proteins within cells, only two enzymes regulate this modification. One of these enzymes is O-GlcNAcase (OGA), a dimeric glycoside hydrolase that has a deep active site cleft in which diverse substrates are accommodated. Chemical tools to control OGA are emerging as essential resources for helping to decode the biochemical and cellular functions of the O-GlcNAc pathway. Here we describe rationally designed bicyclic thiazolidine inhibitors that exhibit superb selectivity and picomolar inhibition of human OGA. Structures of these inhibitors in complex with human OGA reveal the basis for their exceptional potency and show that they extend out of the enzyme active site cleft. Leveraging this structure, we create a high affinity chemoproteomic probe that enables simple one-step purification of endogenous OGA from brain and targeted proteomic mapping of its post-translational modifications. These data uncover a range of new modifications, including some that are less-known, such as O-ubiquitination and N-formylation. We expect that these inhibitors and chemoproteomics probes will prove useful as fundamental tools to decipher the mechanisms by which OGA is regulated and directed to its diverse cellular substrates. Moreover, the inhibitors and structures described here lay out a blueprint that will enable the creation of chemical probes and tools to interrogate OGA and other carbohydrate active enzymes.Artículo Reversible Bimetallic Inhibition to Modulate Selectivity During Catalysis(American Chemical Society, 2024-12-23) Serrano Díez, Emmanuel; Pita Milleiro, Alejandra; Rangel García, Jesús; Moreno Díaz, Juan José; Roselló Merino, Marta; Campos, Jesús; Química Inorgánica; Ministerio de Ciencia e Innovación (MICIN). España; Fundación laCaixa; European Commission (EC)Bimetallic complexes have demonstrated a great ability to enhance the activity of monometallic systems for bond activation and catalysis. In this work, we explore the opposite approach: using a second metal to passivate the activity of another by reversible bimetallic inhibition. To do so we have synthesized a family of nine electrophilic gold complexes of formula Au(PR3)(NTf2) ([NTf2]− = [N(SO2CF3)2]−) that can act as inhibitors in the semihydrogenation of terminal and internal alkynes catalyzed by the iconic iridium Vaska complex IrCl(CO)(PPh3)2. This behavior parallels the well-known passivation effect of lead over palladium in the heterogeneous Lindlard catalyst. Most gold fragments, except for the most hindered, form metal-only Lewis pairs upon combination with iridium, which have been fully characterized and exhibit distinct dative Ir → Au bonds. When applied to alkyne hydrogenation, these bimetallic structures have a clear tendency toward olefin formation, while the monometallic catalyst unselectively leads to overreduction products. Our computational studies not only provide a feasible mechanism for the Ir-only system, but also evince the active role of gold in passivating iridium by reversibly forming heterobimetallic structures that lead to enhanced selectivity.Artículo Deciphering the role of Zn2+-binding histidines from TIA-1 on the assembly and dynamics of stress granules(Wiley, 2024) Corrales Guerrero, Laura; Díaz Moreno, Irene; Bioquímica Vegetal y Biología Molecular; Ministerio de Ciencia e Innovación (MICIN). España; Agencia Estatal de Investigación. EspañaT-cell intracellular antigen-1 (TIA-1) is a key RNA-binding protein that participates in translation regulation and RNA splicing. TIA-1 undergoes Liquid-Liquid Phase Separation (LLPS) as a fundamental mechanism that enables the condensation of RNA and proteins into membraneless organelles called stress granules (SGs). However, this dynamic behavior can lead to aberrant fibril formation, implicated in neurodegenerative disorders, and must be tightly regulated. In this study, we investigated the role in the cell of histidine residues His94 and His96, responsible for Zn2+ binding. Using fluorescence microscopy, we found that the specific binding site formed by these residues is critical for SG assembly. Furthermore, it also plays a role maintaining the dynamic behavior of SG-assembled TIA-1. Collectively, our findings confirm the physiological relevance of TIA-1 His94 and His96 in the Zn2+-mediated regulatory mechanism for protection against fibril formation in SGs13 .
Artículo α-GalCer sp2-Iminoglycolipid Analogs as CD1d-dependent iNKT Modulators: Evaluation of Their Immunotherapeutic Potential in Murine Models of Asthma and Autoimmune Hepatitis(Elsevier, 2024-11-15) Lai, Alan Chuan Ying; González Cuesta, Manuel; Ho, Chieh Hsin; Chi, Po Yu; Wu, Ko Chien; Rocha, Gabriel; Muñoz García, Juan Carlos; Angulo Álvarez, Jesús; García Fernández, José M.; Chang, Ya Jen; Ortiz Mellet, Carmen; Química Orgánica; Ministerio de Ciencia e Innovación (MICIN). España; Agencia Estatal de Investigación. España; Junta de AndalucíaInvariant natural killer T (iNKT) cells are a subset of innate T cells displaying powerful immunomodulatory functions. Despite extensive preclinical research on the use of iNKT agonist and antagonist for various diseases, translating these findings into successful clinical applications has proven challenging, leaving no approved treatments to date. Efforts to optimize therapeutic outcomes by developing alternative glycolipids to α-galactosylceramide (α-GalCer or KRN7000), the prototypical iNKT antigen, have shown improved preclinical results. However, significant obstacles remain, including the relatively laborious synthesis of α-glycosides and their vulnerability to degradation by α-glycosidases. To overcome these limitations, we explored the use of sp2-iminosugars, a class of glycomimetics, to replace the carbohydrate moiety in α-GalCer-like glycolipids. This substitution offers enhanced biostability and precise control over α-selectivity in glycosylation reactions. The resulting sp2-iminoglycolipids (sp2-IGLs) were tested for their immunomodulatory effects, demonstrating the ability to bind the α-GalCer binding site on the CD1d protein in antigen-presenting cells (APCs), and functioning as iNKT antagonists in α-GalCer-stimulated splenocytes. Notably, analogs featuring a 4-alkyl-1,2,3-aminotriazol-1-yl segment in place of the C25 N-acyl tail in α-GalCer additionally exhibited mild agonistic activity in the absence of α-GalCer stimulation. Computational studies support the formation of stable CD1d– sp2-IGL and CD1d – sp2-IGL – T-cell receptor complexes, with significant differences in the dynamics depending on the glycone nature and lipid tail length. These findings provide a molecular rationale for the observed experimental data. Furthermore, in vivo studies using murine models of asthma and autoimmune hepatitis have identified promising sp2-IGL candidates for further development in immunotherapy.Artículo Isoform-specific regulation of PKM by acetylation(National Academy of Sciences, 2025-11-25) Pavlenko, Dariia; Tamargo Azpilicueta, Joaquín; Nudelman, Hila; Ankri, Yuval; Shahar, Anat; Díaz Moreno, Irene; Arbely, Eyal; Bioquímica Vegetal y Biología Molecular; European Union (UE); Israel Science Foundation; Ministerio de Ciencia, Innovación y Universidades (MICIU). EspañaPyruvate kinase (PK) is a crucial glycolytic protein involved in vital cellular processes ranging from cell proliferation to immune responses. The activity and functions of PK are tightly regulated by diverse mechanisms, including posttranslational N -lysine acetylation. Although previous studies have explored the impact of acetylation on selected lysine residues within the M2 isoform of PK (PKM2), a more comprehensive selection of acetylation sites and their respective effects on both PKM2 and the highly homologous PKM1 isoform is lacking. Here, we describe the structural, functional, and regulatory effects of site-specific acetylation on an expanded set of conserved lysines in PKM2 and selected lysines in PKM1. To study homogeneously acetylated proteins, we genetically encoded the incorporation of acetylated lysine into PKM variants expressed in bacteria and cultured mammalian cells. Our integrated biochemical, structural, and computational approach revealed K115 acetylation as an inhibitory modification in both PKM1 and PKM2 that stabilizes a closed active site conformation of the proteins. We also show that, in contrast to K115 acetylation, previously reported acetylation of K305 inhibits PKM2 but has no effect on the activity and oligomerization of PKM1. These findings propose the existence of both uniform and isoform-specific regulatory mechanisms of PKM, mediated by acetylation.Artículo Recent progress of metal–organic frameworks as sensors in (bio) analytical fields: towards real‑world applications(Springer, 2023-01-04) Zuliani, Alessio; Khiar, Noureddine; Carrillo Carrión, Carolina; Química InorgánicaThe deployment of metal–organic frameworks (MOFs) in a plethora of analytical and bioanalytical applications is a growing research area. Their unique properties such as high but tunable porosity, well-defined channels or pores, and ease of postsynthetic modification to incorporate additional functional units make them ideal candidates for sensing applications. This is possible because the interaction of analytes with a MOF often results in a change in its structure, eventually leading to a modification of the intrinsic physicochemical properties of the MOF which is then transduced into a measurable signal. The high porosity allows for the adsorption of analytes very efficiently, while the tunable pore sizes/nature and/or installation of specific recognition groups allow modulating the affinity towards different classes of compounds, which in turn lead to good sensor sensitivity and selectivity, respectively. Some figures are given to illustrate the potential of MOF-based sensors in the most relevant application fields, and future challenges and opportunities to their possible translation from academia (i.e., laboratory testing of MOF sensing properties) to industry (i.e., real-world analytical sensor devices) are critically discussed.Editorial Editorial: Chemistry and the circular economy(2023-12-15) Rizzarelli, Paola; Zuliani, Alessio; Reddy, Narendra; Química InorgánicaArtículo Biocatalytic synthesis of heterobiaryl sulfoxides: a comparative study between Baeyer–Villiger monooxygenases and unspecific peroxygenases(Royal Society of Chemistry, 2026-02-26) Vázquez Domínguez, Pablo; Carrión-González, Julia; García-Requena, Desirée; Fraaije, Marco W.; Loncar, Nikola; Fernández Fernández, Rosario Fátima; Scheibner, Katrin; Gutiérrez, Ana; González-Benjumea, Alejandro; Ros Lao, Abel; Gonzalo Calvo, Gonzalo de; Química Orgánica; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; European Union (UE); Ministerio de Ciencia e Innovación (MICIN). EspañaThe biocatalytic sulfoxidation of heterobiaryl indole- and pyrrole-based sulfides was investigated using unspecific peroxygenases (UPOs) and Baeyer–Villiger monooxygenases (BVMOs) as complementary oxidative biocatalysts. Among the UPOs tested, only the UPO from Marasmius rotula showed outstanding catalytic efficiency, reaching up to 99% conversion at substrate concentrations as high as 60 mM, with excellent chemoselectivity toward sulfoxides (>90%), albeit with moderate enantioselectivities (17–64% ee). In contrast, screening of a panel of BVMOs revealed superior stereochemical control: TmCHMO enabled the sulfoxidation of indole-based sulfides with enantioselectivities up to 94% ee, while OTEMO proved particularly effective for pyrrole-based substrates, affording sulfoxides in up to 90% ee. Reaction parameters such as temperature, pH, cosolvent and substrate loading have been optimized, allowing reaction rates of up to 22.4 mmol L−1 h−1 at 50 mM substrate concentration without enantioselectivity loss. Overall, pyrrole-based sulfides displayed higher optical purities than indole analogues under BVMO catalysis, whereas UPOs excelled in terms of productivity and operational simplicity. Selected BVMO- and UPO-catalyzed reactions were successfully scaled up, demonstrating the practical applicability of these biocatalytic systems. These results highlight the complementary strengths of UPOs and BVMOs for the efficient and selective synthesis of chiral heterobiaryl sulfoxides.Artículo Carbohydrate-Based Hydrogels: Weaving Nature’s Versatility into Biomedical Innovation(Dove Medical Press Ltd, 2026-03-06) Cova, Camilla María; Zuliani, Alessio; Khiar, Noureddine; Química Inorgánica; Ministerio de Ciencia e Innovación (MICIN). España; Junta de Andalucía; Consejo Superior de Investigaciones Científicas (CSIC); European Union (UE)During the past few years, the development of innovative hydrogels for biomedical applications has undergone significant advancements. Among the diverse classes of soft biomaterials, carbohydrate-based hydrogels have attracted particular attention due to their intrinsic biocompatibility, biodegradability, and high versatility in chemical modification. Their structural diversity enables finely tunable biological interactions, and recent approaches increasingly focus on receptor-mediated targeting to improve cellular recognition and therapeutic precision. These properties position carbohydrate-based hydrogels as promising platforms in three major application areas: drug delivery, tissue engineering, and wound healing. In addition, their high water-retention capacity supports favourable healing environments and allows sustained drug release, while their natural origin helps reduce production costs and environmental impact. Despite these advantages, important challenges remain—such as achieving controlled degradation, ensuring long-term mechanical stability, and balancing bioactivity with safety—to fully exploit their clinical potential. To better align with emerging trends, this review also highlights recent advancements involving the integration of carbohydrate-based hydrogels with smart materials and nanocomposites, which are expected to further enhance their performance and expand their biomedical applications. Overall, this review provides a comprehensive overview of current progress in carbohydrate-based hydrogels, emphasizing their bio-interactions, existing limitations, and future directions in this rapidly evolving field.Artículo Multisite phosphorylation of the AML-linked C-terminal of nucleophosmin (NPM1) orchestrates protein stability, DNA binding and charge block-driven phase separation(Oxford University Press, 2026-02-27) Rivero-García, Pablo; Giner Arroyo, Rafael Luis; Tamargo Azpilicueta, Joaquín; Telfer, Abbey; Frezza, Elisa; Velázquez-Campoy, Adrián; Díaz-Moreno, Sofía; Rosa Acosta, Miguel Ángel de la; Díaz Moreno, Irene; Bioquímica Vegetal y Biología Molecular; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Fundación Ramón Areces; Ministerio de Educación. España; Consejo Superior de Investigaciones Científicas (CSIC)Nucleophosmin (NPM1) is a nucleolar protein commonly mutated in ~30% of newly diagnosed acute myeloid leukemia (AML) cases. These mutations occur in the terminal exon of the NPM1 gene, affecting the C-terminal DNA-binding domain of the protein and causing its delocalization to the cytoplasm—a hallmark of NPM1-mutated AML. NPM1 shuttling to the nucleoplasm is tightly regulated by posttranslational modifications, such as phosphorylation of Ser254, Ser260, and Tyr271 of the DNA-binding domain. However, the structural mechanisms underlying this process remain unclear. In this work, we show that Ser-to-Asp (S254D–S260D) and Tyr-to-pCMF (para-carboxymethyl phenylalanine) (Y271pCMF) phosphomimetic mutations induce significant structural and dynamical rearrangements, as well as drastic modifications in electrostatic surface potential. These changes compromise recognition of a G-quadruplex sequence from the c-MYC promoter by reducing DNA-binding affinity, reshape histone capturing dynamics, and fade charge segregation in the histone-binding domain. Combination of such substitutions in a triple phosphomimetic variant (S254D–S260D–Y271pCMF) further destabilizes the domain’s structure and triggers protein aggregation. Altogether, these findings suggest that phosphorylation of Ser254, Ser260, and Tyr271 of the C-end DNA-binding domain weakens both DNA affinity and charge block-driven liquid–liquid phase separation, offering a molecular explanation for the delocalization of NPM1 outside of the nucleolus.Artículo Neutral sp2-iminosugars exploiting non-glycone interactions for selective acid α- and β-glucosidase activity modulation: Pharmacological chaperones for Gaucher and Pompe diseases(Elsevier, 2025-12-16) García Moreno, M. Isabel; Kawakami, Kiyoko; Nanba, Eiji; García Fernández, José M.; Higaki, Katsumi; Ortiz Mellet, Carmen; Química Orgánica; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Agencia Estatal de Investigación. EspañaA major challenge in developing selective active site-directed pharmacological chaperones for lysosomal storage disorders is discriminating among glycosidases acting on anomeric substrates. Here, we report the design and synthesis of neutral thiourea-type sp2-iminosugars derived from 1-deoxynojirimycin to rescue the activity of mutant variants of human acid β-glucosidase (GCase) and acid α-glucosidase (GAA) implicated in Gaucher disease (GD) and Pompe disease (PD), respectively. Structural diversification at the non-glycone substituents enabled fine-tuning of hydrophobic and π-stacking interactions, leading to selective enzyme targeting. In vitro assays and cell-based models demonstrated that aromatic derivatives restored GAA activity, improved autophagic flux, and normalized lysosomal trafficking in PD cells (HAP1-p.G549R cells), whereas aliphatic derivatives enhanced GCase activity and corrected mitochondrial dysfunction in GD fibroblasts (p.F213I and p.N370S fibroblasts). Notably, the N’-(p-methoxyphenyl)thiourea derivative exhibited dual activity, rescuing both GAA and GCase mutants without affecting wild-type enzymes. These results identify neutral thiourea-type sp2-iminosugars as promising scaffolds for next-generation pharmacological chaperones with enhanced selectivity and reduced off-target effects.Artículo Phosphine-functionalized NHC Ni(II) and Ni(0) complexes: synthesis, characterization and catalytic properties(Royal Society of Chemistry, 2017-05-22) Rull, S. G.; Jiménez Rama, Raquel; Álvarez González, Eleuterio; Fructos, M. R.; Belderrain, T. R.; Nicasio Jaramillo, María del Carmen; Química Inorgánica; Ministerio de Economía y Competitividad (MINECO). EspañaTwo families of nickel complexes bearing chelating diphenylphosphine-functionalized NHC ligands [NiII(ArNHCPPh2)(allyl)]Cl 1a (Ar = Mes); 1b, (Ar = 2,6-iPr2-C6H3) and [Ni0(ArNHCPPh2)(alkene)] 2a (Ar = 2,6-iPr2-C6H3, alkene = styrene); 2b (Ar = 2,6-iPr2-C6H3, alkene = diethyl fumarate) have been prepared and fully characterized. VT-NMR experiments in solution reveal that the allyl derivatives 1a–b are stereochemically nonrigid. The solid-state structure of the Ni0 derivative 2b is also reported. These complexes display interesting catalytic properties in various cross-coupling reactions. The precatalyst [Ni0(ArNHCPPh2)(styrene)] 2a was found to be the most active system. The bulkiness of the N-substituent on the imidazole ring and the low oxidation state of the metal center in 2a accounted for its enhanced catalytic performance. This system catalyzed effectively the coupling of (hetero)aryl chlorides with a range of nucleophiles including Grignard reagents, boronic acids, secondary amines and indoles.Artículo Structural and electronic modulation by Ce-doping in MOF-derived In2O3@CeO2-ZrO2 catalysts for CO2 hydrogenation(Elsevier, 2026-01-01) Bracciotti, Edoardo; Salusso, Davide; López-Luque, Iván; Bertinetti, Stefano; Luque-Álvarez, Ligia A.; Bobadilla Baladrón, Luis Francisco; Prieto, Gonzalo; Moliner, Manuel; Bordiga, Silvia; Rojas-Buzo, Sergio; Química Inorgánica; European Union (UE); Ministerio de Ciencia e Innovación (MICIN). EspañaIndium oxide (In2O3) has emerged as a promising catalyst for CO2 hydrogenation to methanol due to its exceptional selectivity compared with conventional Cu-based systems, which typically yield undesired by-products despite higher conversion rates. However, the reduction of In2O3 under reaction conditions limits its long-term stability, motivating the development of robust oxide supports. In this work, we present a systematic study on the influence of cerium concentration in CeO2–ZrO2 supports on the performance of In2O3-based catalysts. A series of In2O3@Ce(100−x)Zrx materials were synthesized via a scalable and reproducible MOF-templated approach using UiO-66(Ce/Zr) precursors and subsequent calcination. Comprehensive characterization by in situ PXRD, XAS and H2-TPR revealed that low cerium incorporation (≈5 %) promotes unique Ce-Zr-In interfacial interactions, enhancing indium oxide dispersion and suppressing its reduction to metallic indium. Catalytic tests under CO2 hydrogenation conditions (25 bar, 513–573 K) demonstrated unprecedented methanol selectivity and stability for the low-Ce composition. These findings highlight the critical role of controlled Ce doping in tuning the structural and electronic properties of CeO2–ZrO2 supports and demonstrate the scalability of MOF-derived synthesis routes for designing next-generation catalysts for sustainable methanol productionArtículo Regioselective Syntheses of Bis(indazolyl)methane Isomers: Controlling Kinetics and Thermodynamics via Tunable Non-Innocent Amines(American Chemical Society, 2025-11-13) Álvarez Sánchez, María; Gómez, Margarita; Santos Hurtado, Carina; Ngoune, Jean; Álvarez, Eleuterio; Galindo del Pozo, Agustín; Pettinari, Claudio; Química Inorgánica; Ministerio de Economía y Competitividad (MINECO). España; Ministerio de Ciencia, Innovación y Universidades (MICIU). EspañaThe selective synthesis of regioisomers from ambident N-heterocycles remains a challenge in organic chemistry. We report a general and modular method for the regioselective syntheses of bis(indazolyl)methane isomers, in which the outcome is controlled by the nature of the base. Specifically, we employed structurally diverse amines as noninnocent bases, whose steric and electronic properties─particularly their pKaH and ability to act as methylene carriers or activators─play a decisive role in directing product distribution. By fine-tuning the amine structure, we achieved selective access to symmetrical and unsymmetrical isomers under mild, one-step conditions, without intermediate isolation. The use of amines over conventional inorganic bases was essential to enable both chemo- and regioselective control, while minimizing overactivation or competing pathways. Experimental findings were supported by DFT calculations that rationalize the observed selectivity through differential activation energies and intermediate stabilities. The methodology accommodates both classical methylenating agents (e.g., CH2Br2) and in situ generated ammonium-based donors. All compounds were fully characterized, and key products were confirmed by single-crystal X-ray diffraction (SCXRD). This strategy highlights the utility of noninnocent amines as tunable reagents for regioselective transformations of ambident nucleophiles, with broad potential applications in ligand design, supramolecular chemistry, and heterocyclic synthesis.