Person: Fernández López, Israel
Universidad Complutense de Madrid
Faculty / Institute
Now showing 1 - 10 of 10
- PublicationSite‐Specific Reduction‐Induced Hydrogenation of a Helical Bilayer Nanographene with K and Rb Metals: Electron Multiaddition and Selective Rb + Complexation(Wiley, 2021-12-07) Zhou, Zheng; Fernández García, Jesús M.; Zhu, Yikun; Evans, Paul J.; Rodríguez, Rafael; Crassous, Jeanne; Wei, Zheng; Fernández López, Israel; Petrukhina, Marina A.; Martín León, Nazario
- PublicationCharacterization of a CholesteroNitrone (ISQ-201), a Novel Drug Candidate for the Treatment of Ischemic Stroke(MDPI, 2020-03-31) Martínez-Alonso, Emma; Escobar-Peso, Alejandro; Ayuso, Maria I.; Gonzalo-Gobernado, Rafael; Chioua, Mourad; Montoya, Juan J.; Montaner, Joan; Fernández López, Israel; Marco-Contelles, José; Alcázar, AlbertoNitrones have a well-recognized capacity as spin-traps and are considered powerful free radical scavengers, which are two important issues in hypoxia-induced oxidative stress and cell death in brain ischemia. Consequently, nitrones have been proposed as therapeutic agents in acute ischemic stroke (AIS). In this paper, we update the biological and pharmacological characterization of ISQ-201, a previously identified cholesteronitrone hybrid with antioxidant and neuroprotective activity. This study characterizes ISQ-201 as a neuroprotective agent against the hypoxia-induced ischemic injury. Transitory four-vessel occlusion and middle cerebral artery occlusion (tMCAO) were used to induce cerebral ischemia. Functional outcomes were determined using neurofunctional tests. Infarct area, neuronal death, and apoptosis induction were evaluated. In addition, ISQ-201 reactivity towards free radicals was studied in a theoretical model. ISQ-201 significantly decreased the ischemia-induced neuronal death and apoptosis, in a dose-dependent manner, showing its therapeutic effect when administered up until 6 h after post-ischemic reperfusion onset, effects that remained after 3 months from the ischemic episode. Furthermore, ISQ-201 significantly reduced infarct volume, leading to recovery of the motor function in the tMCAO model. Finally, the theoretical study confirmed the reactivity of ISQ-201 towards hydroxyl radicals. The results reported here prompted us to suggest ISQ-201 as a promising candidate for the treatment of AIS.
- PublicationOrigin of Catalysis and Selectivity in Lewis Acid-Promoted Diels–Alder Reactions Involving Vinylazaarenes as Dienophiles(ACS Publications, 2022-07-06) Portela García de Blas, Susana; Fernández López, IsraelThe poorly understood factors controlling the catalysis and selectivity in Lewis acid-promoted Diels−Alder cycloaddition reactions involving vinylazaarenes as dienophiles have been quantitatively explored in detail by means of computational methods. With the help of the activation strain model and the energy decomposition analysis methods, it is found that the remarkable acceleration induced by the catalysis is mainly due to a significant reduction of the Pauli repulsion between the key occupied π-molecular orbitals of the reactants and not due to the proposed stabilization of the lowest unoccupied molecular orbital (LUMO) of the dienophile. This computational approach has also been helpful to understand the reasons behind the extraordinary regio- and diastereoselectivity observed experimentally. The insight gained in this work allows us to predict even more reactive vinylazaarene dienophiles, which may be useful in organic synthesis.
- PublicationBonding Situation of σ‐E−H Complexes in Transition Metal and Main Group Compounds(Wiley, 2022-07-28) Ríos, Pablo; Conejero, Salvador; Fernández López, IsraelThe ambiguous bonding situation of σ-E−H (E=Si, B) complexes in transition metal compounds has been rationalized by means of Density Functional Theory calculations. To this end, the combination of the Energy Decomposition Analysis (EDA) method and its Natural Orbital for Chemical Valance (NOCV) extension has been applied to representative complexes described in the literature where the possible η1 versus η2 coordination mode is not unambiguously defined. Our quantitative analyses, which complement previous data based on the application of the Quantum Theory of Atoms in Molecules (QTAIM) approach, indicate that there exists a continuum between genuine η1 and η2 modes depending mainly on the strength of the backdonation. Finally, we also applied this EDA-NOCV approach to related main-group species where the backdonation is minimal.
- PublicationFactors Controlling the Aluminum(I)‐ meta ‐Selective C−H Activation in Arenes(Wiley-VCH, 2021-06-29) Cabrera Trujillo, Jorge Juan; Fernández López, IsraelThe so far poorly understood factors controlling the complete meta-selectivity observed in the C H activation reactions of alkylarenes promoted by aluminyl anions have been explored in detail by means of Density Functional Theory calculations. To this end, a combination of state-ofthe-art computational methods, namely the activation strain model of reactivity and energy decomposition analysis, has been applied to quantitatively unveil the origin of the selectivity of the transformation as well as the influence of the associated potassium cation. It is found that the selectivity takes place during the initial nucleophilic addition step where the key LP(Al)!π*(C=C) molecular orbital interaction is more stabilizing for the meta-pathway, which results in a stronger interaction between the reactants along the entire transformation.
- PublicationSite Selectivity in Pd-Catalyzed Reactions of α-Diazo-α-(methoxycarbonyl)acetamides: Effects of Catalysts and Substrate Substitution in the Synthesis of Oxindoles and β-Lactams(MDPI, 2019-09-30) Solé, Daniel; Pérez-Janer, Ferran; Amenta, Arianna; Bennasar, M.-Lluïsa; Fernández López, IsraelThe Pd-catalyzed intramolecular carbene C–H insertion of α-diazo-α-(methoxycarbonyl)acetamides to prepare oxindoles as well as β-lactams was studied. In order to identify what factors influence the selectivity of the processes, we explored how the reactions are affected by the catalyst type, using two oxidation states of Pd and a variety of ligands. It was found that, in the synthesis of oxindoles, ((IMes)Pd(NQ))2 can be used as an alternative to Pd2(dba)3 to catalyze the carbene CArsp2–H insertion, although it was less versatile. On the other hand, it was demonstrated that the Csp3–H insertion leading to β-lactams can be effectively promoted by both Pd(0) and Pd(II) catalysts, the latter being most efficient. Insight into the reaction mechanisms involved in these transformations was provided by DFT calculations.
- Publicationη 6 ‐Metalated Aryl Iodides in Diels‐Alder Cycloaddition Reactions: Mode of Activation and Catalysis(Wiley, 2023-12-14) Portela García de Blas, Susana; Fernández López, IsraelThe potential application of η6-metalated aryl iodides as organocatalyst has been explored by means of computational methods. It is found that the enhanced halogen bonding donor ability of these species, in comparison with their demetalated counterparts, translates into a significant acceleration of the Diels-Alder cycloaddition reaction involving cyclohexadiene and methyl vinyl ketone. The factors behind this acceleration, the endo-exo selectivity of the process and the influence of the nature of the transition metal fragment in the activity of these species are quantitatively explored in detail by means of the combination of the Activation Strain Model of reaction and the Energy Decomposition Analysis methods.
- PublicationNature of the Hydrogen Bond Enhanced Halogen Bond(MDPI, 2021) Portela, Susana; Fernández López, IsraelThe factors responsible for the enhancement of the halogen bond by an adjacent hydrogen bond have been quantitatively explored by means of state-of-the-art computational methods. It is found that the strength of a halogen bond is enhanced by ca. 3 kcal/mol when the halogen donor simultaneously operates as a halogen bond donor and a hydrogen bond acceptor. This enhancement is the result of both stronger electrostatic and orbital interactions between the XB donor and the XB acceptor, which indicates a significant degree of covalency in these halogen bonds. In addition, the halogen bond strength can be easily tuned by modifying the electron density of the aryl group of the XB donor as well as the acidity of the hydrogen atoms responsible for the hydrogen bond.
- PublicationSobre la Síntesis, Estructura y Reactividad de Complejos Metal-Carbeno: un Estudio Teórico-Experimental(2005-03) Fernández López, Israel; Sierra Rodríguez, Miguel Ángel; Mancheño Real, María JoséEl trabajo realizado en esta tesis doctoral” se enmarca dentro del campo de la química organometálica y su aplicación al desarrollo de nuevos procesos en síntesis orgánica. Dicho trabajo se ha centrado en el estudio de complejos metal-carbeno de tipo Fischer, sustratos de probada versatilidad en síntesis orgánica. La presente tesis doctoral estudia, tanto desde un punto de vista teórico como experimetal, procesos fotoquímicos, sintéticos y estructurales de este tipo de complejos organometálicos.
- PublicationL'Horizon a Gervillii (Bajocien inférieur) de Tendron (Cher, France). Taphonomie et populations d'Ammonites.(Istituto Poligrafico e Zecca Dello Stato, 1994) Fernández López, Israel; Mouterde, RenéLa reprise de l'étude d'un bon affleurement, observé déja anciennement par l'un de nous (R. M.) permet de préciser la correspondance entre les séquences sédimentaires et les unités biostratigraphiques du Bajocien présents dans le Berry oriental ou le Nivernais. Nous avons reconnu des ammonites caractéristiques des biozones a Discites, Laeviuscula, Sauzei, Humphriesianum et Niortense. Notre intérest s'est porté sur une association d'ammonites représentant l'Horizon a Gervillii (Biozone a Humphriesianum). Un banc, bien individualisé lithologiquement (10 a 15 cm), entre deux discontinuités stratigraphiques, a livré une association de coquilles d'ammonites remarquablement conservées; elle est marquée par l'abondance des Sonniniiés (Dorsetensia - Nannina) et des Sphaeroceratidés (Chondroceras), associés a de moins abondants Lissoceratidés (Toxamblyites - Microtoxamblyites, Stegoxyites, Lissoceras), Stéphanocératidés (Skirroceras -Epalxites, Stephanoceras -Itinsaites, Stemmatoceras, Teloceras?,) Oppéliidés (Oppelia - Oecotraustes), et Strigocératidé (Srigoceras - cadomoceras). Parmi ces genres le groupe des Dorsetensia - Nannina est particulierement remarquable. L'abondance des exemplaires permet l'étude de la variabilité des macroconques (D. liostraca, D. subtecta, D. aff. hebridica) et des microconques (N. romani, N. deltafalcata, N, hannoverana) a insi que de leurs rapports éventuels. Des corrélations sont proposées avec les associations analogues reconnues dans l'Allemagne, en Angleterre, dans le sud de la France, en Espagne; dans le nord de l'Italie et la Hongrie.