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

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

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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.
Dual Luminescence and Infrared Circularly Polarized Luminescence up to 900 nm with Platinum Complexes Bearing a Helical Donor-acceptor Ligand
(Royal Society of Chemistry, 2024) Vázquez Domínguez, Pablo; Horojat, M.; Suits, E.; Fernández de Córdova, Francisco José; Vanthuyne, N.; Ros Lao, Abel; Vanthuyne, Nicolas; Jacquemin, Denis; Universidad de Sevilla. Departamento de Química Orgánica; European Union (UE); Consejo Superior de Investigaciones Científicas (CSIC); Ministerio de Ciencia e Innovación (MICIN). España
Chiral molecular materials able to emit circularly polarized luminescence (CPL) have attracted considerable interest in the last few decades, due to the potential of CP-light in a wide range of applications. While CP luminescent molecules with blue, green, and yellow emissions are now well-reported, NIR CPL from organic and organometallic compounds lags behind due to the dual challenge of promoting radiative deexcitation of the excited state in this low energy region while assuring a significant magnetic dipole transition moment, a prerequisite for generating CPL. Based on a versatile axially chiral arylisoquinoline ligand, we report the synthesis and chiroptical properties of chiral donor-acceptor platinum(ii) complexes displaying CPL that extends up to almost 900 nm. Interestingly, these emitters show both fluorescence and phosphorescence emissions in solution, with intensities depending on the charge-transfer character of the organic ligand. Experimental and theoretical investigations show that this feature strongly impacts the intersystem crossing event between the singlet and triplet excited states of these complexes and the related phosphorescence lifetime. The effect is less important regarding the CPL, and most complexes show luminescence dissymmetry factors with values up to ca. 2 × 10−3 around 800 nm.
Catalytic Atroposelective Synthesis of C−N Axially Chiral Aminophosphines via Dynamic Kinetic Resolution
(John Wiley and Sons, 2024) Rodríguez Franco, Carlos; Roldán Molina, E.; Aguirre Medina, A.; Fernández Fernández, Rosario Fátima; Hornillos, Valentín; Lassaletta, José M.; Universidad de Sevilla. Departamento de Química Inorgánica; Ministerio de Ciencia e Innovación (MICIN). España; Junta de Andalucía; Universidad de Granada
A ruthenium-catalyzed reductive amination via asymmetric transfer hydrogenation (ATH) has been used to perform an efficient dynamic kinetic resolution (DKR) of N-aryl 2-formyl pyrroles decorated with a phosphine moiety positioned at the ortho’ position. The strategy relies on the labilization of the stereogenic axis in the substrate facilitated by a transient Lewis acid-base interaction (LABI) between the carbonyl carbon and the phosphorus center. The reaction features broad substrate scope of aliphatic amines and N-aryl pyrrole scaffolds, and proceeds under very mild conditions to afford P,N atropisomers in good to high yields and excellent enantioselectivities (up to 99 % ee) for both diphenyl and dicyclohexylphosphino derivatives.
Reversible Redox Ligand-Centered Reactivity in 2,6-Bisiminopyridine Aluminum Systems
(American Chemical Society, 2024) Delgado Collado, Juan Manuel; Videa, Hellen; Serrano Laguna, Pablo J.; Fuentes, M. Ángeles; Álvarez, Eleuterio; Díaz Quintana, Antonio Jesús; Martínez Martínez, Antonio J.; Rodríguez Delgado, Antonio; Campora, Juan; Universidad de Sevilla. Departamento de Química Inorgánica; Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular; Ministerio de Ciencia e Innovación (MICIN). España; Thematic Network "OASIS"; Junta de Andalucía; Universidad de Huelva; Agencia Estatal de Investigación. España
We report the synthesis of cationic 2,6-bisiminopyridine organoaluminum complexes, [(BIP)AlR2]+, as stable BArF4- or PF6- salts, and their reversible single-electron reduction into well-defined paramagnetic species, [(BIP·)AlR2]. Four redox couples, [(BIP)AlR2]+/0, have been fully characterized through structural, spectroscopic, electrochemical and computational techniques.
Mechanochemistry for Organic and Inorganic Synthesis
(American Chemical Society, 2024) Reynes, Javier F.; León García, Félix; García, Felipe; Universidad de Sevilla. Departamento de Química Inorgánica; Agencia Estatal de Investigación. España; Fundación para el Fomento en Asturias de la Investigación Científica Aplicada y la Tecnología (FICYT); The Marie Skłodowska-Curie Actions (MSCA)
In recent years, mechanochemistry has become an innovative and sustainable alternative to traditional solvent-based synthesis. Mechanochemistry rapidly expanded across a wide range of chemistry fields, including diverse organic compounds and active pharmaceutical ingredients, coordination compounds, organometallic complexes, main group frameworks, and technologically relevant materials. This Review aims to highlight recent advancements and accomplishments in mechanochemistry, underscoring its potential as a viable and eco-friendly alternative to conventional solution-based methods in the field of synthetic chemistry.
Finely Tunable Carbon Nanofiber Catalysts for the Efficient Production of HMF in Biphasic MIBK/H2O Systems
(Multidisciplinary Digital Publishing Institute (MDPI), 2024) Bounoukta, Charf Eddine; Megías Sayago, Cristina; Rendón Márquez, Nuria; Ammari, F.; Centeno, M. A.; Ivanova, Svetlana; Universidad de Sevilla. Departamento de Química Inorgánica; Ministerio de Ciencia e Innovación (MICIN). España
This work proposes catalytic systems for fructose dehydration to 5-hydroxymethylfurfural using a series of functionalized carbon nanofibers. The catalysts were synthesized via finely selected covalent grafting in order to include a variety of functionalities like pure Bronsted acid, tandem Brønsted/Lewis acid, and tandem Lewis acid/Lewis base catalysts. After the characterization and evaluation of acidity strength and the amount of acid centers, the catalyst series was screened and related to the product distribution. The best-performing catalyst was also used to optimize the reaction parameters in order to achieve 5-hydroxymethylfurfural yields rounding at 60% without significant humin formation.
Atroposelective Transfer Hydrogenation of Biaryl Aminals via Dynamic Kinetic Resolution. Synthesis of Axially Chiral Diamines
(American Chemical Society, 2021-03-18) Carmona, José A.; Rodríguez Franco, Carlos; López Serrano, Joaquín; Ros Lao, Abel; Iglesias Sigüenza, Francisco Javier; Fernández Fernández, Rosario; Lassaletta, José M.; Hornillos, Valentín; Universidad de Sevilla. Departamento de Química Inorgánica; Universidad de Sevilla. Departamento de Química orgánica; Ministerio de Ciencia e Innovación (MICIN). España; Junta de Andalucía
An efficient dynamic kinetic resolution (DKR) approach for the synthesis of axially chiral diamines has been developed on the basis of a ruthenium-catalyzed enantioselective transfer hydrogenation. The strategy relies on the configurational instability of cyclic biaryl aminal precursors in equilibrium with their amino-imine open forms, as supported by DFT calculations. This protocol features a broad substrate scope of aliphatic amines and biaryl scaffolds and proceeds under very mild conditions, allowing the preparation of BINAM homologues in good to high yields and nearly perfect enantioselectivities (up to 99% ee).
A combined experimental and computational study to decipher complexity in the asymmetric hydrogenation of imines with Ru catalysts bearing atropisomerizable ligands
(Royal Society of Chemistry, 2021-01-21) León García, Félix; Comas-Vives, Aleix; Álvarez González, Eleuterio; Pizzano, Antonio; Universidad de Sevilla. Departamento de Química Inorgánica; Ministerio de Ciencia e Innovación (MICIN). España
RuCl2(P-OP)(N-N) complexes (1) containing an atropisomerizable phosphine-phosphite (P-OP) and a chiralC2symmetric diamine (N-N) are readily prepared astransisomers by successive addition of P-OP and N-N ligands to RuCl2(PPh3)3. For these complexes, fast atropisomerization of the biaryl fragment at room temperature has been observed. Compoundtrans-1acleanly isomerizes into a mixture ofcisisomers in EtOH upon heating. DFT calculations reproduce accurately the ratio of isomers observed as well as the greater thermodynamic stability of thecisisomers of1a. Complexes1are efficient catalyst precursors for the asymmetric hydrogenation ofN-aryl imines5in toluene under very mild conditions using KOtBu as a base (4 bar H2, room temperature,5/1/KOtBu = 500/1/10). Among the catalyst precursors,1fprovides good enantioselectivities in the hydrogenation of a wide range ofN-aryl imines (84-96% ee, 16 examples). From DFT calculations, a mechanism consisting in stepwise transfer of a hydride and a proton from the dihydride to the imine has been proposed, with the most favourable paths forRandSproducts involvingcis-dihydridesd1Randd3S, respectively. Among several hydrogen activation pathways examined in thepro-Rroute, the most favorable one consists of hydrogen coordination to a Ru-amido/amine adduct, followed by amine assisted activation of dihydrogen.
Full Potential of Microwave-assisted Processes: From Synthesis of High-quality MIL-101(Fe) Catalyst to Furfural Valorization
(Elsevier, 2024) Franco, Ana; Rodríguez Gómez, Salvador; Hamad, Said; Carrillo Carrión, Carolina; Universidad de Sevilla. Departamento de Química orgánica; Gobierno de España; Ministerio de Ciencia e Innovación (MICIN). España
Metal-organic frameworks (MOFs) have emerged as promising catalysts in biomass valorization processes, due to mainly their high structural and chemical flexibility when compared to other catalytic materials. However, it is still challenging to achieve perfect control in the synthetic method to obtain high-quality MOF particles containing uniform active sites, which will strongly influence their further catalytic performance. Herein, we have demonstrated that microwaves (MWs) can play a key role not only in the preparation of the MOF catalyst, specifically MIL-101(Fe), but also in performing the MOF-catalyzed oxidative esterification of furfural to methyl-2-furoate under mild conditions and in the absence of a base. MIL-101(Fe) exhibited a high conversion of furfural (>90 %) and excellent selectivity to methyl-2-furoate (>95 %) in just 1 h of reaction and at a moderate temperature (60 °C). A series of control experiments and DFT-mechanistic studies revealed the pivotal role played by the MIL-101(Fe) particles to drive the preferential formation of the target compound methyl-2-furoate, and evidenced that the MOF behaves as a truly heterogeneous catalyst. Overall, this work demonstrates that the potential of MW energy is underexploited, and highlights that there is still a long way to go in the development of new MOF-based catalytic approaches for biomass transformations.
Phosphorylation of cytochrome c at tyrosine 48 finely regulates its binding to the histone chaperone SET/TAF-Iβ in the nucleus
(Wiley, 2024-11-16) Tamargo Azpilicueta, Joaquín; Casado Combreras, Miguel Ángel; Giner Arroyo, Rafael Luis; Velázquez Campoy, Adrián; Márquez Escudero, Inmaculada; Olloqui Sariego, José Luis; Rosa Acosta, Miguel Ángel de la; Díaz Moreno, Irene; Universidad de Sevilla. Departamento de Química Física; Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular; Ministerio de Ciencia, Innovación y Universidades (MICINN). España; European Union (UE); Junta de Andalucía
Post-translational modifications (PTMs) of proteins are ubiquitous processes present in all life kingdoms, involved in the regulation of protein stability, subcellular location and activity. In this context, cytochrome c (Cc) is an excellent case study to analyze the structural and functional changes induced by PTMS as Cc is a small, moonlighting protein playing different roles in different cell compartments at different cell-cycle stages. Cc is actually a key component of the mitochondrial electron transport chain (ETC) under homeostatic conditions but is translocated to the cytoplasm and even the nucleus under apoptotic conditions and/or DNA damage. Phosphorylation does specifically alter the Cc redox activity in the mitochondria and the Cc non-redox interaction with apoptosis-related targets in the cytoplasm. However, little is known on how phosphorylation alters the interaction of Cc with histone chaperones in the nucleus. Here, we report the effect of Cc Tyr48 phosphorylation by examining the protein interaction with SET/TAF-Iβ in the nuclear compartment using a combination of molecular dynamics simulations, biophysical and structural approaches such as isothermal titration calorimetry (ITC) and nuclear magnetic resonance (NMR) and in cell proximity ligation assays. From these experiments, we infer that Tyr48 phosphorylation allows a fine-tuning of the Cc-mediated inhibition of SET/TAF-Iβ histone chaperone activity in vitro. Our findings likewise reveal that phosphorylation impacts the nuclear, stress-responsive functions of Cc, and provide an experimental framework to explore novel aspects of Cc post-translational regulation in the nucleus.

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