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

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

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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). España
The 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.
Tautomerisation of 2-Substituted Pyridines to N-Heterocyclic Carbene Ligands Induced by the 16 e- Unsaturated [TpMe2IrIII(C6H5)2] Moiety
(Wiley, 2012-04-10) Conejero Iglesias, Salvador; López Serrano, Joaquín; Paneque Sosa, Margarita; Petronilho, Ana; Poveda, Manuel L.; Vattier Lagarrigue, María Florencia; Álvarez González, Eleuterio; Carmona Guzmán, Ernesto; Química Inorgánica; Ministerio de Ciencia e Innovación (MICIN). España; Junta de Andalucía
The complex [Tp Me2Ir(C 6H 5) 2(N 2)] reacts with several 2-substituted pyridines to generate N-heterocyclic carbenes resulting from a formal 1,2-hydrogen shift from C 6 to N. In this paper we provide a detailed report of the scope and the mechanistic aspects (both experimental and theoretical) of the tautomerisation of 2-substituted pyridines.
Metallacyclic Pyridylidene Structures from Reactions of Terminal Pyridylidenes with Alkenes and Acetylene
(Wiley, 2010-04-28) Álvarez González, Eleuterio; Hernández, Yohar A.; López Serrano, Joaquín; Maya Díaz, Celia María; Paneque Sosa, Margarita; Petronilho, Ana; Poveda, Manuel L.; Salazar, Verónica; Vattier Lagarrigue, María Florencia; Carmona Guzmán, Ernesto; Química Inorgánica; Ministerio de Ciencia e Innovación (MICIN). España; Junta de Andalucía; Portuguese FCT; Consejo Nacional de Ciencia y Tecnología (CONACYT). México
(Chemical Equotion Present). Iridium pyridyl species are key intermediates in the title reactions. Thermal elimination of benzene from complexes 1 (R = Me, Ph) creates a vacant coordination site accessible to unsaturated hydrocarbons. Subsequent intramolecular nucleophilic attack by the pyridyl nitrogen atom to the alkene or vinylidene leads to iridacyclic pyridylidene structures (see scheme).
Dicoordinate Au(I)−Ethylene Complexes as Hydroamination Catalysts
(American Chemical Society, 2022-03-23) Navarro, Miquel; González Alférez, Macarena; Sousa, Morgane de; Miranda Pizarro, Juan; Campos, Jesús; Química Inorgánica; European Research Council (ERC); Ministerio de Ciencia e Innovación (MICIN). España
A series of gold(I)–ethylene π-complexes containing a family of bulky phosphine ligands has been prepared. The use of these sterically congested ligands is crucial to stabilize the gold(I)–ethylene bond and prevent decomposition, boosting up their catalytic performance in the highly underexplored hydroamination of ethylene. The precatalysts bearing the most sterically demanding phosphines showed the best results reaching full conversion to the hydroaminated products under notably mild conditions (1 bar of ethylene pressure at 60 °C). Kinetic analysis together with density functional theory calculations revealed that the assistance of a second molecule of the nucleophile as a proton shuttle is preferred even when using an extremely congested cavity-shaped Au(I) complex. In addition, we have measured a strong primary kinetic isotopic effect that is consistent with the involvement of X–H bond-breaking events in the protodeauration turnover-limiting step.
Multiple C-B Bond Cleavage Reactions at [BArF 4]- Anions Mediated by Terphenyl Phosphine Gold Catalysts
(American Chemical Society, 2025-01-13) Miranda Pizarro, Juan; Navarro, Miquel; Campos, Jesús; Química Inorgánica; Ministerio de Ciencia e Innovación (MICIN). España; Junta de Andalucía
Fluorinated borates have been widely used as innocent and weakly coordinating counteranions. Among those, [BArF4]− ([B(C6H3-3,5-(CF3)2)4]−) occupies a prominent position due to the robustness of its B–C carbon bonds. Herein, we investigate C–B bond cleavage in the [BArF4]− anion mediated by cationic gold fragments of type [Au(PMe2Ar′)]+, where Ar′ stands for bulky terphenyl (C6H3-2,6-Ar2) substituents. In addition, we have exploited the stoichiometric B–C bond cleavage to construct a catalytic cycle for the synthesis of boranes under acidic conditions.
Non-bifunctional Mn catalysts based on phosphine-phosphites for the hydrogenation of carbonyl substrates
(Royal Society of Chemistry, 2025-09-22) Jiménez, Verónica; González, Carmen; López Serrano, Joaquín; Fernández de Córdova, Francisco; Pizzano, Antonio; Química Inorgánica; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; European Union (UE)
A series of Mn(I) complexes bearing phosphine–phosphite ligands (P-OP) of formula [Mn(Br)(P-OP)(CO)3] (1) have been prepared and characterised. These compounds exist in solution as a mixture of fac and mer isomers with fac/mer ratios from 18 : 1 to 2 : 1. The relatively low donor ability of P-OP compared to bis(trialkylphosphines) or bis–NHC ligands, typically found in non-bifunctional Mn catalysts reported to date, is evinced in IR spectra. Compounds 1 provide efficient catalysts for the hydrogenation of carbonyl substrates using KOtBu as a base. Notably, these complexes constitute a set of modularly designed precatalysts and optimisation of the P-OP ligand provided appropriate catalysts for the reduction of a wide variety of aldehydes and ketones under mild reaction conditions (S/C = 250–500, 20 bar H2, RT to 40 °C). A mechanistic study combining spectroscopic and computational results provides support for a catalyst activation process based on the nucleophilic attack of the alkoxide on a coordinated CO in [Mn(OtBu)(P-OP)(CO)3], as well as a non-bifunctional inner-sphere hydrogenation pathway in the representative hydrogenation of benzophenone. The catalytic cycle is also characterised by a rather stable pentacoordinated alkoxide [Mn(k1-O–OCHPh2)(P-OP)(CO)2] which determines the energetic span of the reaction.
Insights into the Controlled Formation of Zr‐Based Metal–Organic Gels: Linking Macroscopic Properties with Molecular Information from Solution State NMR
(Wiley, 2026-01-19) Muñoz García, Juan Carlos; Moscoso, Francisco G.; Sánchez Fernández, Elena Matilde; Santos García, Jenifer; Angulo Álvarez, Jesus; Carrillo Carrión, Carolina; Química Orgánica; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; European Union; European Commission (EC)
Understanding and controlling the formation mechanisms of metal–organic gels is crucial for their rationaldesign with well-deﬁned properties for diverse applications. However, rapid methodologies enabling atomic-resolutionstructural characterization of gel formation are still largely lacking. Here, we report for the ﬁrst time the molecular-level characterization of the in-situ formation of a Zr-based metal–organic gel by monitoring solvent structuration duringgelation using solvent-observed nuclear magnetic resonance (NMR) spectroscopy. UiO-66-type gels were optimized undermild conditions, i.e., 40 °C and in the absence of acidic modulators, providing a biocompatible environment suitable forthe in-situ encapsulation of sensitive biomolecules during gelation. The combined analysis of saturation transfer differenceand spin diffusion transfer difference NMR growth curves enabled real time monitoring of nucleation and gelation stages,revealing an excellent correlation between the progressive structuration of water within the gel network and the resultingmacroscopic properties. Furthermore, we demonstrate that this NMR approach allows tracking of the in-situ encapsulationof therapeutic biomolecules within the gel, exempliﬁed by a glycolipid with anti-inﬂammatory properties
A step further in our commitment to support early career researchers (ECRs)
(John Wiley and Sons Inc, 2026-01) Fuentes, Sara; Rosa Acosta, Miguel Ángel de la; Bioquímica Vegetal y Biología Molecular
As a not-for-profit open access journal, FEBS Open Bio is proud to support the scientific community not only through the publication of open access articles available to all but also through the charitable activities of FEBS. In this editorial, we look back at some of the highlights of the past year and look forward to the new initiatives planned for 2026—all aimed at supporting our community, the scientific community.
Flash Communication: Strained and Bimetallic Structures of Rhodium and Iridium Germyl Complexes with Phosphinoamido Ligands
(American Chemical Society (ACS), 2025-11-25) Bajo Velázquez, Sonia; Fernández Buenestado, Marta; López Serrano, Joaquín; Campos, Jesús; Química Inorgánica; European Union (UE); Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Agencia Estatal de Investigación. España
In the coordination chemistry of heavier tetrylenes (:ER2, where E = Si, Ge, Sn, Pb), chelating P,N-donor ligands occupy a privileged position, though phosphinoamido ligands, [R2P−NR′] −, have been barely investigated. Herein, we report the synthesis and structural characterization of such complexes, whose structures drastically differ depending on the group 9 metal precursor used. Strained four-membered {P−N−Ge−M} metallacycles (M = Rh, Ir) are produced from the reaction of phosphinoamido germylenes with [MCl2Cp*]2 precursors (Cp* = η5 -C5Me5). At variance, [MCl(COD)]2 dimers are not broken apart; instead, they afford bimetallic species featuring bridging phosphinoamido−germyl and chloride ligands between the two metals. All new compounds were isolated on a preparative scale and spectroscopically characterized and their structures confirmed by X-ray diffraction. Computational studies support the σ-donor character of the Ge−M interaction and the absence of significant πbackbonding.
2D Assemblies Based on a Tetraphenylethylene D,L-Cyclic Peptide Scaffold
(Wiley, 2025-11-10) Bayón-Fernández, Alfonso; Torrón-Celada, Alba; Méndez Ardoy, Alejandro; Coste, Maëva; Delgado-Gestoso, David; Ulrich, Sébastien; Montenegro, Javier; Granja, Juan R.; Química Orgánica; Agencia Estatal de Investigación. España; Xunta de Galicia; Centro de investigación do Sistema universitario de Galicia; Ministerio de Economía y Competitividad (MINECO). España; French National Research Agency (ANR)
Two dimensional (2D) materials and aggregation-induced emission (AIE) fluorophores have recently gained attention due to their unique properties and application potential. However, the combination of AIE probes into 2D self-assembled systems under nanometric control remains elusive due to the sensitivity of supramolecular assemblies to subtle changes in the monomer structure. Herein, we present a new scaffold based on four nanotube-forming cyclic peptide (CP) units attached to a tetraphenylethene (TPE) core whose pH-dependent self-assembly results in light-emitting 2D nanosheets. An oxime bond connection was exploited to synthesize a discrete library of tetrakis-(cyclopeptide) tetraphenylethene monomers that self-assemble into 2D macrotubular nanoarrays under the suitable external stimulus. This new tetrameric CP motif tolerates a broad range of molecular modifications, both on the peptide backbone and TPE core, without compromising the integrity of the 2D self-assembly. We also discovered that adjusting the molecular structure of the TPE aromatic core enabled precise height control of the supramolecular nanosheets. The alignment of the histidine residues within neighboring CPs allowed the application of 2D nanoarchitectures as enzyme mimics with esterase activity. The excellent tolerance to molecular diversity in both the external CP moiety and the internal aromatic AIE core, invites the design of new functional 2D supramolecular materials.
Amplified Detection of Breast Cancer Autoantibodies Using MUC1-Based Tn Antigen Mimics
(American Chemical Society, 2020-07-16) Guillén-Poza, Pablo A.; Sánchez Fernández, Elena Matilde; Artigas, Gerard; García Fernández, José Manuel; Hinou, Hiroshi; Ortiz Mellet, Carmen; Nishimura, Shin Ichiro; Garcia-Martin, Fayna; Química Orgánica; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Ministerio de Economía y Competitividad (MINECO). España
In many human carcinomas, mucin-1 (MUC1) is overexpressed and aberrantly glycosylated, resulting in the exposure of previously hidden antigens. This generates new patient antibody profiles that can be used in cancer diagnosis. In the present study, we focused on the MUC1-associated Tn antigen (α-O-GalNAc-Ser/Thr) and substituted the GalNAc monosaccharide by a glycomimic to identify MUC1-based glycopeptides with increased antigenicity. Two different glycopeptide libraries presenting the natural Tn antigen or the sp2-iminosugar analogue were synthesized and evaluated with anti-MUC1 monoclonal antibodies in a microarray platform. The most promising candidates were tested with healthy and breast cancer sera aiming for potential autoantibody-based biomarkers. The suitability of sp2-iminosugar glycopeptides to detect anti-MUC1 antibodies was demonstrated, and serological experiments showed stage I breast cancer autoantibodies binding with a specific unnatural glycopeptide with almost no healthy serum interaction. These results will promote further studies on their capabilities as early cancer biomarkers.
Interaction of the VP8* protein of a bovine rotavirus C with the H type-2 antigen and its precursor N-acetyl-lactosamine
(Elsevier, 2026-01) Navarro-Lleó, Noemi; Ramírez Cárdenas, Jonathan; Paredes-Martínez, Francisco; Serna, Sonia; Gozalbo-Rovira, Roberto; Muñoz García, Juan Carlos; Reichardt, Niels C.; Casino, Patricia; Angulo Álvarez, Jesús; Rodríguez-Díaz, Jesús; Buesa, Javier; Química Orgánica; Ministerio de Ciencia e Innovación (MICIN). España; Instituto de Salud Carlos III; Generalitat Valenciana; Agencia Estatal de Investigación. España; Gobierno Vasco; European Union (UE)
Rotaviruses (RVs) are the main cause of viral diarrhea among infants, small children, and the young of many animal species. Histo-blood group antigens (HBGAs) are potential RV receptors and glycan composition on mucous surfaces influences host susceptibility and cross-species virus transmission. RVs exhibit genotype-dependent glycan binding and differences are due to sequence modifications in the VP8* domain of the spike protein VP4. Nevertheless, the molecular bases for this genotype-dependent glycan specificity, especially in non-A RVs, are not thoroughly understood. This study delves into how genotypic variations configure a novel binding site in the VP8* of a bovine P[3] rotavirus species C (RVC) strain to recognize H type-2 antigen (H2) and its precursor N-acetyl-lactosamine (LacNAc) using glycan binding assays, crystallography, and STD NMR. Results reveal a specific interaction of bovine P[3] RVC VP8* with H2 and LacNAc, more strongly with the latter. In the P[3] RVC VP8*-H2 interaction, the N-acetyl glucosamine moiety displays significant interaction, while galactose participates moderately and fucose binds weakly. Moreover, the bovine VP8* structure, resolved at 3 Å, shows specific structural features which differ from human RVC, as it contains two additional β-strands (β1 and β2) contributing to β-sheet2 and conformational changes that widens the cleft to allow different carbohydrate binding modes. These subtle changes in both sequence and structure explain the H2 precursor recognition, which is abundant in the human neonate intestine and in human and bovine milk, providing insights into P[3] RVC tropism and its potential zoonotic transmission.
Electric field-induced functional changes in electrode-immobilized mutant species of human cytochrome c
(Elsevier, 2022-10-01) Olloqui Sariego, José Luis; Pérez Mejías, Gonzalo; Márquez Escudero, Inmaculada; Guerra Castellano, Alejandra; Calvente Pacheco, Juan José; Rosa Acosta, Miguel Ángel de la; Andreu Fondacabe, Rafael Jesús; Díaz Moreno, Irene; Química Física; Bioquímica Vegetal y Biología Molecular; Ministerio de Ciencia e Innovación (MICIN). España; Junta de Andalucía; Universidad de Sevilla
Post-translational modifications and naturally occurring mutations of cytochrome c have been recognized as a regulatory mechanism to control its biology. In this work, we investigate the effect of such in vivo chemical modifications of human cytochrome c on its redox properties in the adsorbed state onto an electrode. In particular, tyrosines 48 and 97 have been replaced by the non-canonical amino acid p-carboxymethyl-L-phenylalanine (pCMF), thus mimicking tyrosine phosphorylation. Additionally, tyrosine 48 has been replaced by a histidine producing the natural Y48H pathogenic mutant. Thermodynamics and kinetics of the interfacial electron transfer of wild-type cytochrome c and herein produced variants, adsorbed electrostatically under different local interfacial electric fields, were determined by means of variable temperature cyclic film voltammetry. It is shown that non-native cytochrome c variants immobilized under a low interfacial electric field display redox thermodynamics and kinetics similar to those of wild-type cytochrome c. However, upon increasing the strength of the electric field, the redox thermodynamics and kinetics of the modified proteins markedly differ from those of the wild-type species. The mutations promote stabilization of the oxidized form and a significant increase in the activation enthalpy values that can be ascribed to a subtle distortion of the heme cofactor and/or difference of the amino acid rearrangements rather than to a coarse protein structural change. Overall, these results point to a combined effect of the single point mutations at positions 48 and 97 and the strength of electrostatic binding on the regulatory mechanism of mitochondrial membrane activity, when acting as a redox shuttle protein.
Turning the Tables: Ligand-Centered Hydride Shuttling in Organometallic BIP–Al Systems
(ACS, 2025-07-24) Delgado Collado, Juan Manuel; Fernández de Córdova, Francisco José; Palma, Pilar; Cámpora Pérez, Juan; Rodríguez Delgado, Antonio; Química Inorgánica; Ministerio de Ciencia e Innovación (MICIN). España; European Union (UE); Junta de Andalucía
The reversible storage and release of hydride equivalents remains a central challenge in the design of biomimetic redox systems. Cationic 2,6-bis(imino)pyridine organoaluminum complexes [(4-R-BIP)AlR2]+ (where R = H; R′ = Me, 1a; R′ = Et, 1b; R = Bn; R′ = Me, 1c) and their neutral 2,6-bis(imino)-4-R-dihydropyridinate counterparts [(4-R-HBIP)AlR2] 2a-c are presented as chemically reversible hydride exchangers. Interconversion between these systems is achieved through strong reducing agents such as M+[HBEt3]− (where M = Li; Na) or LiAlH4, while powerful electrophiles like B(C6F5)3 or cationic trityl salts Ph3C+ enable the reverse transformation, with the latter providing complete selectivity. Overall, this reversible hydride exchange mirrors natural NAD(P)H/NADP+ cofactor system. These findings establish a new platform for ligand-centered hydride shuttling, where the metal fragment acts as a passive modulator─inverting the traditional roles assigned to metal and ligand.
Protocols for Monitoring Condensate Formation and Dynamics between the Phase-separating Proteins SET/TAF-Iβ and Cytochrome c
(Elsevier, 2025) Casado Combreras, Miguel Ángel; Rosa Acosta, Miguel Ángel de la; Díaz Moreno, Irene; Bioquímica Vegetal y Biología Molecular; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Junta de Andalucía; Ministerio de Educación. España
The targeting of several nuclear stress-response factors by translocated cytochrome c upon genotoxic stress has been demonstrated in recent years to involve liquid-liquid phase separation. This protocol addresses the need to investigate the mechanisms and features of phase separation of the histone chaperone SET/TAF-Iβ induced by cytochrome c. We provide steps for protein purification and fluorescent labeling, condensate formation, imaging, quantification, and evaluation of their dynamics by fluorescence recovery after photobleaching (FRAP). This protocol can be broadly applied to other protein complexes.
Effect of Electrostatic Immobilization on the Electrochemistry of Human and Horse Cytochrome c
(Elsevier, 2025) Olloqui Sariego, José Luis; Márquez Escudero, Inmaculada; Guerra Castellano, Alejandra; Molero Casado, Miguel; Rosa Acosta, Miguel Ángel de la; Calvente Pacheco, Juan José; Díaz Moreno, Irene; Andreu Fondacabe, Rafael Jesús; Química Física; Ministerio de Ciencia, Innovación y Universidades (MICIU). España
Protein film voltammetry is a sensitive tool to characterize the electron transfer properties of redox proteins in a variety of environments and conformational states. Here, a detailed voltammetric study aimed to explore the effect of electrostatic immobilization on the electron transfer thermodynamics and kinetics of adsorbed human- and horse- cytochrome c was carried out. For this purpose, the two cytochromes were adsorbed on thiol monolayers (SAM) with different immobilization strengths and donor–acceptor distances. While thermodynamic redox parameters do not seem to be affected by the monolayer thickness and charge density, electron transfer kinetics are significantly modulated by the protein immobilization strength. Stronger protein–SAM electrostatic interactions result in lower electron transfer rates in both non-adiabatic and friction kinetic regimes. This behavior is further characterized by smaller pre-exponential factors and activation enthalpies in Arrhenius type plots. These kinetic results in the physiologically relevant non-adiabatic electron transfer regime are shown to be consistent with the recently developed Matyushov's theoretical formulation of protein electron transfer. Moreover, a comparison between the kinetic parameters of the two cytochrome variants supports the hypothesis that differences between their electron transfer rates originate in their structural flexibility to accommodate the conformational changes required to form the precursor complex between cytochrome and a negatively charged redox partner.
Light-responsive glycosidase inhibitors: Tuning enzyme selectivity and switching factors through integrated chemical and optoglycomic strategies
(Elsevier, 2025-07-15) Rivero Barbarroja, Gonzalo; Maisonneuve, Stéphane; Xie, Juan; García Fernández, José Manuel; Ortiz Mellet, Carmen; Química Orgánica; Ministerio de Ciencia, Innovación y Universidades (MICIU). España
Photopharmacology leverages light-responsive drugs to achieve spatiotemporal control over their activation and interactions with biological targets. This high level of precision is particularly crucial for therapeutic strategies that require sequential drug-target binding and dissociation, such as pharmacological chaperones (PCs) for lysosomal storage disorders (LSDs). PCs must tightly bind misfolded glycosidases in the endoplasmic reticulum (ER) to promote proper folding, yet efficiently dissociate in the lysosome to restore enzymatic function. Here, we demonstrate that azobenzene-equipped, photoswitchable sp2-iminosugars can fulfill these criteria by exploiting differential E-/Z-isomer interactions with aglycone-accommodating regions of target glycosidases. A diversity-oriented strategy was implemented, incorporating variations in glycomimetic portions, linkers, azobenzene substitution patterns, distal substituents, and valency to fine-tune light and temperature responsiveness. This approach yielded derivatives capable of selectively switching between α- and β-glucosidase inhibition, as well as conjugates exhibiting reversible nanomolar inhibition of human glucocerebrosidase, the dysfunctional enzyme in Gaucher disease, with remarkable switching factors under conditions that mirror the scenario at the ER and the lysosome. The results expand the scope of optoglycomics by providing a framework for designing photocommutators that enable reversible glycosidase modulation and laying the foundation for next-generation photoresponsive glycosidase inhibitors with therapeutic potential in LSDs and broader biomedical applications.
Exploring a Novel Anti-Inflammatory Therapy for Diabetic Retinopathy Based on Glyco-Zeolitic-Imidazolate Frameworks
(Multidisciplinary Digital Publishing Institute (MDPI), 2025-06-17) Díaz Paredes, Elena; Martín Loro, Francisco; Rodríguez Marín, Rocío; Gómez Jaramillo, Laura; Sánchez Fernández, Elena Matilde; Carrillo Carrión, Carolina; Arroba, Ana I.; Química Orgánica; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Instituto de Salud Carlos III
Diabetic retinopathy is an ocular disease caused by changes in the expression of inflammatory mediators and increased oxidative stress in the retina and is the leading cause of vision loss in diabetic patients. Currently, there is no treatment capable of reversing retinal damage, which represents a significant burden on the quality of life of patients. (1R)-1-Dodecylsulfonyl-5N,6O-oxomethylidenenojirimycin stands outs as a prototype of the sp2-iminoglycolipids family for its beneficial neuroprotective effect against this chronic eye disease. Critical issues related to the low solubility and bioavailability of this glycolipid in biological settings are overcome by its encapsulation in a Zeolitic-Imidazolate Framework (ZIF) structure, resulting in homogeneous and biocompatible GlycoZIF nanoparticles. Cell studies show an enhanced cellular uptake compared with the free glycolipid, and importantly, its bioactivity is preserved once released inside cells. Methods: Extensive in vitro and ex vivo assays with diabetic retinopathy models unveil the mechanistic pathways of the designed GlycoZIF. Results: A reduction in proinflammatory mediators, increased heme oxygenase-1 level, inhibition of NLRP3 inflammasome, and reduced reactive gliosis is shown. Conclusions: These findings demonstrate for the first time the potential of Glyco-modified ZIFs for the treatment of diabetes-related ocular problems by controlling the immune-mediated inflammatory response.
Selective H/D Exchange in E–H (E = Si, Ge, Sn) Bonds Catalyzed by 1,2,3-Triazolylidene-Stabilized Nickel Nanoparticles
(American Chemical Society, 2025) Molinillo, Pablo; Gálvez Del Postigo, Ana; Puyo, Maxime; Vattier Lagarrigue, María Florencia; Beltrán, Ana M.; Rendón Márquez, Nuria; Lara Muñoz, Patricia; Suárez, Andrés; Química Inorgánica; Ingeniería y Ciencia de los Materiales y del Transporte; Ministerio de Ciencia e Innovación (MICIN). España; European Union (UE)
Nickel nanoparticles (Ni·MIC) stabilized with mesoionic 1,2,3-triazolylidene (MIC) ligands were prepared via decomposition of the [Ni(COD)2] (COD = 1,5-cyclooctadiene) complex with H2 (3 bar) in the presence of 0.2 or 0.5 equiv of ligand. The obtained monodisperse and small-sized (3.2–3.8 nm) nanoparticles were characterized by high-resolution transmission electron microscopy (TEM, HRTEM) and inductively coupled plasma (ICP) analysis. Further analysis of the nickel nanoparticles by X-ray photoelectron spectroscopy (XPS) demonstrated the coordination of the MIC ligands to the metal surface. Finally, the Ni·MIC nanoparticles were applied in the isotopic H/D exchange in hydrides of group 14 elements (Si, Ge, Sn) using D2 gas under relatively mild conditions (1.0–1.8 mol % Ni, 1 bar D2, 55 °C). High and chemoselective deuterium incorporation at the E–H (E = Si, Ge, Sn) bond in these derivatives was observed.
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.; 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

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