Examinando por Autor "Osorio, Edison"
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- PublicaciónAcceso abiertoAmaryllidaceae alkaloids in skin cancer management: Photoprotective effect on human keratinocytes and anti-proliferative activity in melanoma cells(2023-03-31) Castañeda, Carol; Bravo, Karent; Cortés, Natalie; Bedoya, Janeth; Borges, Warley de S.; Bastida, Jaume; Osorio, EdisonSkin cancer has high rates of mortality and therapeutic failure. In this study, to develop a multi-agent strategy for skin cancer management, the selective cytotoxicity of several alkaloid fractions and pure alkaloids isolated from Amaryllidaceae species was evaluated in melanoma cells. In addition, UVB-stimulated keratinocytes (HaCaT) were exposed to seven alkaloid fractions characterized by GC-MS, and the production of intracellular reactive oxygen species (ROS) and IL-6, were measured to evaluate their photoprotection effects. The Eucharis caucana (bulb) alkaloid fraction (20 μg/ml) had a clear effect on the viability of melanoma cells, reducing it by 45.7% without affecting healthy keratinocytes. This alkaloid fraction and tazettine (both at 2.5 μg/ml) suppressed UVB-induced ROS production by 31.6% and 29.4%, respectively. The highest anti-inflammatory potential was shown by the Zephyranthes carinata (bulb) alkaloid fraction (10 μg/ml), which reduced IL-6 production by 90.8%. According to the chemometric analysis, lycoramine and tazettine had a photoprotective effect on the UVB-exposed HaCaT cells, attenuating the production of ROS and IL-6. These results suggest that Amaryllidaceae alkaloids have photoprotective and therapeutic potential in skin cancer management, especially at low concentrations.
- PublicaciónSólo datosAntiaging activity, molecular docking, and prediction of percutaneous absorption parameters of quinoline–hydrazone hybrids(Medicinal Chemistry Research, 2019-11-01) Osorio, Edison; Bravo, Karent; Cardona, Wilson; Yepes, Andrés; Osorio, Edison H.; Coa, Juan C.The application of antiaging agents can contribute to the prevention and control of skin photoaging. In the current research, nine quinoline–hydrazone hybrids were synthesized to obtain biologically active compounds as possible antiaging agents. The compounds were tested through a comprehensive in vitro evaluation of antielastase, anticollagenase, and antihyaluronidase activities along with the determination of their potential to quench reactive oxygen species (ROS) by the ORAC method. The selected hybrids were subsequently tested on human dermal fibroblasts (HDF) to reveal possible UVB photoprotective activity. The most potent antiaging protection of all the prepared compounds was shown by the trihydroxylated quinoline–hydrazones 5 and 9, which showed the best collagenase inhibition (IC50 = 39.4 and 45.6 µM, respectively). Compound 5 also showed activity against elastase and hyaluronidase (IC50 = 164.2 and 318.8 µM, respectively). The molecular docking results suggest that the difference of inhibition between 5 and 9 is principally attributed to the hydrogen bonds interactions in the residues His218 and His228, and Zn atom in collagenase, Val216 in elastase and Tyr75 in hyaluronidase. In addition, compounds 5 and 9 were able to significantly protect human skin cells from UVB radiation in vitro. These compounds significantly decreased UVB-induced MMP-1 and ROS production and inhibited the suppression of type I procollagen synthesis in cultured HDF. The in silico dermatopharmacokinetic parameters showed promising results. Therefore, our study presented promising results for antiaging drug discovery, focusing on quinoline–hydrazone hybrids as dual inhibitors of skin aging-related enzymes, antioxidants, and inhibitors of the biological effects of UVB irradiation.
- PublicaciónSólo datosCarbon rings decorated with group 14 elements: new aromatic clusters containing planar tetracoordinate carbon(New Journal of Chemistry, 2019-04-03) Yañez, Osvaldo; Vásquez-Espinal, Alejandro; Báez-Grez, Rodrigo; Rabanal-León, Walter A.; Osorio, Edison; Ruiz, Lina; Tiznado, WilliamA simple and chemically intuitive approach is used to design ptC-containing E–C clusters (E = Si–Pb). This approach consists in replacing three or two consecutive protons from an aromatic hydrocarbon by one E24+ or one E2+ fragment, respectively. In the model, electrons from E are removed from the pz orbitals, emptying them. Si–Pb favors the formation of a 3c-2e (E–C–E) σ-bond, which involves the ptC. Additionally, the π-electronic cloud is delocalized through the E-pz orbitals allowing the E atoms to effectively take part in the electronic delocalization, preserving the 4n + 2 Hückel's rule from the parent hydrocarbon. Two aromatic monocycles and one aromatic bicycle – benzene (C6H6), cyclopentadienyl anion (C5H5−) and pentalene dianion (C8H62−) – have been transformed into C–E systems. After an extensive exploration of their potential energy surfaces, four new global minima with ptC are identified, resulting from the substitution of the protons by Si and Ge cations in C5H5− and C8H62− (E3C5 and E4C8). The analysis of both the chemical bonding and the magnetic response to an external magnetic field confirms the aromatic character of these species.
- PublicaciónAcceso abiertoChemical bonding analysis on MgEH15 (E = Sc and Y), highly stable clusters for hydrogen storage(2022-11-30) Ferraro, Franklin; Barboza, Cristina A.; Osorio, EdisonMagnesium based alloys containing scandium and yttrium are promising materials for hydrogen storage devices due to the hydrogen absorption and desorption kinetic and thermodynamic properties, results showing the reversibility of the hydrogenation reaction and leads to a long-lasting energy source. Nevertheless, to the best of our knowledge, there are no theoretical studies comparing the stability between Y and Sc-doped systems available in the literature. In this contribution, we report an analysis of stability and chemical bonding nature for a series of complexes MgEHn (E = Sc and Y, where n = 10 –16) with the aim to understand the nature of binding between a hydrogen molecule and the core system of the metal blend. The results obtained suggest that yttrium-bonded hydrogen molecules are more labile for a dehydrogenation step in comparison to those with scandium. Additionally, based on QTAIM and EDA-NOCV calculations, we conclude that alloys containing scandium are predicted to be more tightly bonded to H2 molecules than those with yttrium. Consequently, the dehydrogenation reaction would be more thermodynamically favorable for the latter
- PublicaciónSólo datosChemical Profiling and Cholinesterase Inhibitory Activity of Five Phaedranassa Herb. (Amaryllidaceae) Species from Ecuador(Molecules, 2020-04-30) Moreno, Raúl; Tallini, Luciana R.; Salazar, Cristina; Osorio, Edison; Montero, Evelin; Bastida, Jaume; Oleas, Nora H.; Acosta León, KarenIt is estimated that 50 million people in the world live with dementia, 60–70% of whom suffer from Alzheimer’s disease (AD). Different factors are involved in the development of AD, including a reduction in the cholinergic neurotransmission level. The Amaryllidaceae plant family contains an exclusive, large, and still understudied alkaloid group characterized by a singular skeleton arrangement and a broad spectrum of biological activities. The chemistry and biodiversity of Ecuadorian representatives of the Phaedranassa genus (Amaryllidaceae) have not been widely studied. In this work, five Ecuadorian Phaedranassa species were examined in vitro for their activity towards the enzymes acetyl- (AChE) and butyrylcholinesterase (BuChE), and the alkaloid profile of bulb extracts was analyzed by GC-MS. The species Phaedranassa cuencana and Phaedranassa dubia showed the most AChE and BuChE inhibitory activity, respectively. To obtain insight into the potential role of the identified alkaloids in these inhibitory effects, docking experiments were carried out, and cantabricine showed in silico inhibitory activity against both cholinesterase structures. Our results show that Amaryllidaceae species from Ecuador are a potential source of new drugs for the palliative treatment of AD.
- PublicaciónSólo datosCrystal structure, Hirshfeld surface analysis and DFT studies of N-(4-acetylphenyl)quinoline-3-carboxamide(Journal of Molecular Structure, 2021-11-15) Polo-Cuadrado, Efraín; Ferrer, Karoll; Osorio, Edison; Brito, Iván; Cisterna, Jonathan; Gutiérrez, MargaritaCrystalline organic compound, N-(4-acetylphenyl)quinoline-3-carboxamide (4) was readily prepared using our previously reported experimental procedure by the reaction of quinoline-3-carboxylic acid (1) with thionyl chloride to generate the acid chloride in situ followed by the coupling itself with 4-aminoacetophenone (3). This report describes the in-depth structural analysis thereof. The spectral characterization was done using FT-IR, 1H-NMR, 13C-NMR and UV-Vis spectroscopy, while its 3D-structure confirmed unambiguously by single crystal X-ray diffraction. The title compound crystallizes in the monoclinic system with the P21/c space group, Z = 4. The crystal packing is mainly controlled by N–H•••O, and C–H•••O hydrogen bond interactions. Molecular geometry optimizations were conducted using the DFT method at the B3LYP/6-31G+(d,p) level of theory and the theoretical UV-Vis spectrum was found to be in good agreement with the experimental spectrum.
- PublicaciónSólo datosDouble-Ring Epimerization in the Biosynthesis of Clavulanic Acid(Journal of Physical Chemistry A, 2020-11-02) Gómez, Sara; Ramírez-Malule, Howard; Cardona-G, Wilson; Osorio, Edison; Restrepo, AlbeiroAll reaction steps during the biosynthesis of suicidal clavulanic acid (coformulated with β-lactam antibiotics and used to fight bacterial infections) are known, except for the crucial 3S,5S → 3R,5R double epimerization needed to produce a biologically active stereoisomer, for which mechanistic hypothesis is subject to debate. In this work, we provide evidence for a reaction channel for the double inversion of configuration that involves a total of six reaction steps. When mediated by an enzyme with a terminal S–H bond, this highly complex reaction is spontaneous in the absence of solvents. Polarizable continuum models introduce reaction barriers in aqueous environments because of the strong destabilization of the first transition state. Molecular geometries and electronic structures in both cases indicate that solvent-free spontaneity and aqueous medium barriers are both firmly rooted in a substantial reorganization of the electron density right at the onset of the reaction, mostly involving a cyclic evolution/involution of large regions of π delocalization used to stabilize the excess charge left after the initial proton abstraction.
- PublicaciónSólo datosDouble-Ring Epimerization in the Biosynthesis of Clavulanic Acid(Journal of Physical Chemistry A, 2020-10-02) Gómez, Sara; Ramírez-Malule, Howard; Cardona-G, Wilson; Osorio, Edison; Restrepo, AlbeiroAll reaction steps during the biosynthesis of suicidal clavulanic acid (coformulated with β-lactam antibiotics and used to fight bacterial infections) are known, except for the crucial 3S,5S → 3R,5R double epimerization needed to produce a biologically active stereoisomer, for which mechanistic hypothesis is subject to debate. In this work, we provide evidence for a reaction channel for the double inversion of configuration that involves a total of six reaction steps. When mediated by an enzyme with a terminal S–H bond, this highly complex reaction is spontaneous in the absence of solvents. Polarizable continuum models introduce reaction barriers in aqueous environments because of the strong destabilization of the first transition state. Molecular geometries and electronic structures in both cases indicate that solvent-free spontaneity and aqueous medium barriers are both firmly rooted in a substantial reorganization of the electron density right at the onset of the reaction, mostly involving a cyclic evolution/involution of large regions of π delocalization used to stabilize the excess charge left after the initial proton abstraction.
- PublicaciónSólo datosExploring the Potential Energy Surface of Trimetallic Deltahedral Zintl Ions: Lowest-Energy [Sn6Ge2Bi]3– and [(Sn6Ge2Bi)2]4– Structures(Inorganic Chemistry, 2019-07-09) Báez-Grez, Rodrigo; Garza, Jorge; Vásquez-Espinal, Alejandro; Osorio, Edison; Rabanal-León, Walter A.; Yañez, Osvaldo; Tiznado, WilliamThe synthesis and structural characterization of the dimer [(Sn6Ge2Bi)2]4– raise the possibility of obtaining a broad variety of analogous compounds with different Sn/Ge/Bi proportions. Several combinations of nine atoms have been detected by electrospray mass spectrometry as potential assembly units. However, [(Sn6Ge2Bi)2]4– remains as the unique experimentally characterized species in this series. This fact has motivated us to explore its potential energy surface, as well as its monomers’ [Sn6Ge2Bi]3–/2–, in an effort to gain insight into the factors that might be privileging the experimental viability of this species. Our results show that the lowest-energy [Sn6Ge2Bi]3– structure remains in its oxidized product [Sn6Ge2Bi]2–, which corresponds to that identified in the dimer [(Sn6Ge2Bi)2]4–. Additionally, local minima, very close in energy to the lowest-energy monomer, are chiral mixtures that dimerize into diverse structures with a probable energetic cost, making them noncompetitive isomers. Finally, the global minimum of the dimer [(Sn6Ge2Bi)2]4– presents the most stable monomers as assembly units. These results show the importance of considering the simultaneity of all of these conditions for the viability of these types of compounds.
- PublicaciónSólo datosMicrosatellites, morphological, and alkaloids characterization of Zephyranthes fosteri and Z. alba (Amaryllidaceae): Allopatric populations(Biochemical Systematics and Ecology, 2022-03-15) Centeno-Betanzos, Lucia Y.; López-Caamal, Alfredo; Cortés Rendon, Natalie; León Santiago, Mayra; Osorio, Edison; Bastida Armengol, Jaume; Cano-Santana, Zenón; Reyes-Chilpa, Ricardo; Tovar-Sánchez, EfraínZephyranthes (Amaryllidaceae) is a taxonomically complex genus due to the frequent overlap of interspecific morphological variation. In Mexico, Z. alba and Z. fosteri are herbaceous plants that, when distributed in sympatry, generate individuals with complex patterns of morphological variation, leading to taxonomic confusion. Therefore, it is necessary to first characterize these species in allopatric populations. In this contribution, molecular, morphological, and alkaloid profiles were used to characterize both species in allopatric sites. Our results show that Z. alba and Z. fosteri allopatric populations are two well-defined genetic and morphological groups. Flower-related characters were the ones that best allowed us to distinguish between species. In a similar fashion, the alkaloid profile showed remarkable differences among species: four alkaloids were specific to Z. alba and five to Z. fosteri. Lycorine (43.3-88.8%) and galanthamine (87.7-91.4%) were the most abundant alkaloids for each species, respectively. In conclusion, Z. fosteri and Z. alba exhibit noticeable differences when distributed in allopatry. In addition, Z. fosteri has greater genetic and phenotypic plasticity compared to Z. alba, which could be related to the former's ability to colonize new habitats. Finally, the molecular, genetic and chemical markers developed here will provide a framework to further studies aiming to explore if hybridization among Z. alba and Z. fosteri occurs in sympatric populations.
- PublicaciónSólo datosRevisiting the Rearrangement of Dewar Thiophenes(Molecules, 2020-01-10) Gómez, Sara; Osorio, Edison; Dzib, Eugenia; Islas, Rafael; Restrepo, Albeiro; Merino, GabrielThe mechanism for the walk rearrangement in Dewar thiophenes has been clarified theoretically by studying the evolution of chemical bonds along the intrinsic reaction coordinates. Substituent effects on the overall mechanism are assessed by using combinations of the ring (R = H, CF3) and traveling (X = S, S = O, and CH2) groups. The origins of fluxionality in the S–oxide of perfluorotetramethyl Dewar thiophene are uncovered in this work. Dewar rearrangements are chemical processes that occur with a high degree of synchronicity. These changes are directly related to the activation energy.
- PublicaciónSólo datosStructural, thermodynamic and kinetic factors in the desorption/absorption of a hydrogen molecule in the M3AlH10−xNa (M = Be or Mg; x = 0 or 2) hydrides(New Journal of Chemistry, 2019-10-28) Osorio, Edison; García-Beltrán, Olimpo; Giraldo, Carolin; Ferraro, Franklin; Hadad, CacierIn the context of the design and study of new materials for hydrogen storage, in this work structural, compositional, thermodynamic and kinetic-mechanistic factors for the desorption/absorption of a hydrogen molecule in the M3AlH10−xNa (M = Be or Mg; x = 0 or 2) hydrides are evaluated. The results show that the mechanisms of hydrogen detachment/attachment are energetically more favorable when the two involved hydrogen atoms are related to different metals in each system. The hydrogenation of M3AlH8Na occurs very easily at relatively low temperatures. The most convenient values of temperature and rate constants for thermal dehydrogenation are reached for the Be3AlH10Na system in tetrahedral geometry. These factors, together with the fact that this structure is quite symmetrical, make the tetrahedral Be3AlH10Na a good candidate as an assembly unit for suprastructures. However, our results indicate that the dehydrogenation temperature is rather high; so, future studies about ways to facilitate Be3AlH10Na dehydrogenation, such as its catalysis or its support on some surface, are necessary for energy-based uses.
- PublicaciónSólo datosStructure–antioxidant activity relationships in boldine and glaucine: a DFT study(New Journal of Chemistry, 2021-01-17) Vásquez-Espinal, Alejandro; Yañez, Osvaldo; Osorio, Edison; Areche, Carlos; García-Beltrán, Olimpo; Ruiz, Lina M.; Cassels, Bruce K.; Tiznado, WilliamPrevious experimental results on the free radical-scavenging properties of boldine, one of the most potent natural antioxidants, suggested that the benzylic hydrogen, neighboring a nitrogen lone electron pair, might be the key to its protective and antioxidant effect, in contrast to the usually assumed labile phenolic hydrogen atoms. Our computations suggest that both boldine and glaucine can undergo two successive hydrogen transfers under attack by an oxidizing radical (from C-6a-H and C-7-H). The hydroxyl groups of boldine could also participate via the HAT mechanism, although to a lesser extent. In the case of quaternary N-methylated derivatives, the sharing of the nitrogen lone pair makes the transfer of the C-6a hydrogen energetically unfeasible, supporting the earlier proposal based on experimental evidence. The hydroxyl groups of boldine and its derivatives could contribute to antioxidant activity via the sequential proton loss electron transfer mechanism, although this would only be relevant at higher pH values.
- PublicaciónAcceso abiertoSynthesis multicomponent based on o‐tolyl‐isocyanide; cholinesterase inhibitors and computational studies(2022-05-16) Camargo-Ayala, Lorena; Polo-Cuadrado, Efraín; Osorio, Edison; Soto-Delgado, Jorge; Duarte, Yorley; Prent-Peñaloza, Luis; Gutiérrez, MargaritaIsocyanide-based multicomponent reactions turn out to be interesting synthetic strategies, with highly valued advantages such as atomic economy, selectivity, among others. Furthermore, Isocyanide-based multicomponent reactions have been shown to generate a wide range of products with significant biological activity. Recently, it has been described that the compounds of the Isocyanide-based multicomponent reactions product could be inhibitors of cholinesterase enzymes, acetylcholinesterase, and butyrylcholinesterase. cholinesterase enzymes have aroused great interest as pharmacological targets in the treatment of Alzheimer's disease, which is a disease that affects millions of people in the world, and its effects become disabling for those who suffer from it since it mainly has consequences on memory and cognitive ability. In this work, using Isocyanide-based multicomponent reactions, we report a series of five new compounds, their characterization, and their potential inhibitory biological activity on acetylcholinesterase and butyrylcholinesterase by spectrophotometric analysis. Our studies revealed that the compounds have moderate inhibitory activities against acetylcholinesterase and butyrylcholinesterase. Interestingly, compounds 7a and 7e showed a higher affinity for butyrylcholinesterase. Particularly compound 7a proved to be the compound with the best activity of this series with an IC50 of 25.91 µM for butyrylcholinesterase, more than 62.22 times selective for butyrylcholinesterase than for acetylcholinesterase. The study of molecular docking and molecular dynamics revealed that the hydrophobic character of these compounds favors the interaction with BChE. The favored interactions for compounds 7a and 7e are with the hydrophobic residues Trp82, Trp231, Val288, Phe329, Thr120. In addition, the molecular electrostatic potential and pharmacokinetic predictions also showed that compounds 7a and 7e have free energy values close to galantamine in the complex with butyrylcholinesterase, among others. These analyzes will allow us in the future to establish some structural modifications that would enable, on this basis, to obtain compounds with better activity against cholinesterase enzymes
- PublicaciónSólo datosSynthesis, characterization, crystal and molecular structure and theoretical study of N-(naphthalen-1-yl)-2-(piperidin-1-yl) acetamide, a selective butyrylcholinesterase inhibitor(Journal of Molecular Structure, 2022-01-15) Camargo-Ayala, Lorena; Prent-Peñaloza, Luis; Polo-Cuadrado, Efraín; Brito, Iván; Cisterna, Jonathan; Osorio, Edison; González, Wendy; Gutiérrez, MargaritaIn this study, we reported for the first time the crystalline and molecular structure of the compound N-(naphthalen-1-yl) -2- (piperidin-1-yl) acetamide. The synthesis of the compound was carried out by amidation using a coupling reagent (N, N'-diisopropylcarbodiimide) and subsequently amination. The compound was experimentally characterized by UV-visible spectroscopy, 13C-NMR, 1H-NMR, melting point, and X-ray diffraction technique. In addition, we include here, theoretical studies on boundary molecular orbitals, descriptors global reactivity, natural bond orbital analysis, Hirshfeld surface analysis, energy framework and molecular docking. Interestingly, acetamide shows a keto form in the solid state, as reported in similar monosubstituted acetamide compounds. The dihedral angles are negligible, being essentially coplanar between the fragment. Additionally, inhibitory activity studies were carried out for the enzymes acetylcholinesterase and butyrylcholinesterase, obtaining an IC50 of 426.14 ± 18.54 µM and 5.12 ± 0.02 µM, respectively, thus having significant selectivity for butyrylcholinesterase with an IC50 lower than that reported for the reference compound galantamine (7.96 ± 0.8 µM). Our consistent molecular coupling analyzes show the formation of a more stable complex between compound 5 and butyricholinesterase due to the complementary interactions of compound 5′s naphthyl ring with residues Trp 231 and Phe 329 compared to the complex formed with acetylcholinesterase.
- PublicaciónSólo datosTheobroma cacao L. compounds: Theoretical study and molecular modeling as inhibitors of main SARS-CoV-2 protease(Biomedicine and Pharmacotherapy, 2021-04-25) Yañez, Osvaldo; Osorio, Manuel Isaías; Areche, Carlos; Vasquez-Espinal, Alejandro; Bravo, Jessica; Sandoval-Aldana, Angélica; Pérez-Donoso, José M.; González-Nilo, Fernando; Matos, Maria João; Osorio, Edison; García-Beltrán, Olimpo; Tiznado, WilliamCocoa beans contain antioxidant molecules with the potential to inhibit type 2 coronavirus (SARS-CoV-2), which causes a severe acute respiratory syndrome (COVID-19). In particular, protease. Therefore, using in silico tests, 30 molecules obtained from cocoa were evaluated. Using molecular docking and quantum mechanics calculations, the chemical properties and binding efficiency of each ligand was evaluated, which allowed the selection of 5 compounds of this series. The ability of amentoflavone, isorhoifolin, nicotiflorin, naringin and rutin to bind to the main viral protease was studied by means of free energy calculations and structural analysis performed from molecular dynamics simulations of the enzyme/inhibitor complex. Isorhoifolin and rutin stand out, presenting a more negative binding ΔG than the reference inhibitor N-[(5-methylisoxazol-3-yl)carbonyl]alanyl-l-valyl-N~1~-((1R,2Z)−4-(benzyloxy)−4-oxo-1-{[(3R)−2-oxopyrrolidin-3-yl]methyl}but-2-enyl)-L-leucinamide (N3). These results are consistent with high affinities of these molecules for the major SARS-CoV-2. The results presented in this paper are a solid starting point for future in vitro and in vivo experiments aiming to validate these molecules and /or test similar substances as inhibitors of SARS-CoV-2 protease.
- PublicaciónSólo datosTheoretical Study of the Antioxidant Activity of Quercetin Oxidation Products(Frontiers in Chemistry, 2019-11-27) Vásquez-Espinal, Alejandro; Yañez, Osvaldo; Osorio, Edison; Areche, Carlos; García-Beltrán, Olimpo; Ruiz, Lina María; Cassels, Bruce K.; Tiznado, WilliamIt was recently shown that, when tested in cellular systems, quercetin oxidized products (Qox) have significantly better antioxidant activity than quercetin (Q) itself. The main Qox identified in the experiments are either 2,5,7,3′,4′-pentahydroxy-3,4-flavandione (Fl) or its tautomer, 2-(3,4-dihydroxybenzoyl)-2,4,6-trihydroxy-3(2H)-benzofuranone (Bf). We have now performed a theoretical evaluation of different physicochemical properties using density functional theory (DFT) calculations on Q and its main Qox species. The most stable structures (for Q and Qox) were identified after a structural search on their potential energy surface. Since proton affinities (PAs) are much lower than the bond dissociation enthalpies (BDEs) of phenolic hydrogens, we consider that direct antioxidant activity in these species is mainly due to the sequential proton loss electron transfer (SPLET) mechanism. Moreover, our kinetic studies, according to transition state theory, show that Q is more favored by this mechanism. However, Qox have lower PAs than Q, suggesting that antioxidant activity by the SPLET mechanism should be a result of a balance between proclivity to transfer protons (which favors Qox) and the reaction kinetics of the conjugated base in the sequential electron transfer mechanism (which favors Q). Therefore, our results support the idea that Q is a better direct antioxidant than its oxidized derivatives due to its kinetically favored SPLET reactions. Moreover, our molecular docking calculations indicate a stabilizing interaction between either Q or Qox and the kelch-like ECH-associated protein-1 (Keap1), in the nuclear factor erythroid 2-related factor 2 (Nrf2)-binding site. This should favor the release of the Nrf2 factor, the master regulator of anti-oxidative responses, promoting the expression of the antioxidant responsive element (ARE)-dependent genes. Interestingly, the computed Keap1-metabolite interaction energy is most favored for the Bf compound, which in turn is the most stable oxidized tautomer, according to their computed energies. These results provide further support for the hypothesis that Qox species may be better indirect antioxidants than Q, reducing reactive oxygen species in animal cells by activating endogenous antioxidants.
- PublicaciónSólo datosUnique magnetic shielding and bonding in Pnicogen nortricyclane Zintl clusters(Chemical Physics Letters, 2020-06-16) Parida, Rakesh; Reddy, G. Naresh; Osorio, Edison; Muñoz-Castro, Alvaro; Giri, SantanabUsing first principle calculations, in-depth bonding and aromaticity pattern of bare anionic nortricyclane, E73− (E = P, As, Sb, and Bi) Zintl clusters have been explored. A detailed topological analysis reveals that every cluster comprises of nine 2c-2e σ-bond with an occupation number of 1.96–1.99 |e|. We find an impressive covalence in the E73− cluster which decreases down the group from P73− to Bi73−. The nucleus independent chemical shift (NICS) foretell about the aromatic property of the Zintl cluster which is also decreasing along the group. In addition, the response with respect to external magnetic field of the nucleus independent shielding tensor was obtained to explore the possible formation of the shielding cone behavior.