Examinando por Autor "Mena-Ulecia, Karel"

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    Insights into the interactions between maleimide derivates and GSK3β combining molecular docking and QSAR
    (Public Library of Science, 2014-07) Quesada-Romero, Luisa; Mena-Ulecia, Karel; Tiznado, William; Caballero, Julio
    Many protein kinase (PK) inhibitors have been reported in recent years, but only a few have been approved for clinical use. The understanding of the available molecular information using computational tools is an alternative to contribute to this process. With this in mind, we studied the binding modes of 77 maleimide derivates inside the PK glycogen synthase kinase 3 beta (GSK3b) using docking experiments. We found that the orientations that these compounds adopt inside GSK3b binding site prioritize the formation of hydrogen bond (HB) interactions between the maleimide group and the residues at the hinge region (residues Val135 and Asp133), and adopt propeller-like conformations (where the maleimide is the propeller axis and the heterocyclic substituents are two slanted blades). In addition, quantitative structure–activity relationship (QSAR) models using CoMSIA methodology were constructed to explain the trend of the GSK3b inhibitory activities for the studied compounds. We found a model to explain the structure–activity relationship of non-cyclic maleimide (NCM) derivatives (54 compounds). The best CoMSIA model (training set included 44 compounds) included steric, hydrophobic, and HB donor fields and had a good Q2 value of 0.539. It also predicted adequately the most active compounds contained in the test set. Furthermore, the analysis of the plots of the steric CoMSIA field describes the elements involved in the differential potency of the inhibitors that can be considered for the selection of suitable inhibitors.
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    Insights into the selective sensing mechanism of a luminescent Cd(II)-based MOF chemosensor toward NACs: roles of the host–guest interactions and PET processes
    (Springer, 2021-05) Hidalgo-Rosa, Yoan; Mena-Ulecia, Karel; Treto-Suarez, Manuel; Schott, Eduardo; Páez-Hernández, Dayán; Zarate, Ximena
    The structural and photophysical properties of the [Cd2(H2L)2(H2O)5].5H2O (where H4L is the ligand 5,5'-((thiophene-2,5-dicarbonyl)bis(azanediyl))diisophthalic acid labeled as Cd-MOF), as well as the elucidation of the selective turn-off luminescent sensing mechanism toward 4-nitroaniline (pNA) were addressed, using quantum chemical methods. To reach this aim, the structures of the ground state (S0) and first excited state (S1) Cd-MOF/analyte system were assessed. We found that after the interaction a photoinduced electron transfer (PET) from the Cd-MOF to pNA is responsible for the fluorescence quenching in this system. For this purpose, a study was performed based on TD-DFT and multireference calculations to corroborate that an excited state exists with the adequate electronic configuration for PET process in the interacting system Cd-MOF/analyte. Intermolecular interaction between the Cd-MOF and analyte was studied by means of Morokuma–Ziegler energy decomposition analysis, natural orbitals of chemical valence, ab initio molecular dynamics (AIMD) calculations and non-covalent interactions (NCI) index. These results showed that intermolecular interactions via hydrogen bond are considerably strengthened in the excited state for the Cd-MOF/pNA, which favor the non-radiative deactivation channels of the chemosensor. In addition, the overlap of absorption spectra of Cd-MOF and pNA indicates that the loss of fluorescence is also due to internal filter effect (IFE). The most noteworthy aspect of this methodology is to consider the relative energies of the S0 and S1 states of MOF/analyte system to explaining the experimental behavior of Cd-MOF toward 4-nitroaniline, proving to be a robust tool in the accurate elucidation of the sensing mechanism in the MOF chemosensor. Graphical abstract: [Figure not available: see fulltext.] Ab initio methods along with TD-DFT have been used to elucidate the selective turn-off luminescent sensing mechanism of nitroaromatic compounds by a Cd-based metal–organic framework (MOF). The role of the host–guest interaction has been pointed out using different theoretical descriptors. A theoretical protocol is given to get more insights into the MOF design and selectivity for nitroaromatic compounds. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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    Kinetic study of removal heavy metal from aqueous solution using the synthetic aluminum silicate
    (Nature Research, 2020-12) Treto-Suárez, Manuel Alejandro; Prieto-García, Julio Omar; Mollineda-Trujillo, Ángel; Lamazares, Emilio; Hidalgo-Rosa, Yoan; Mena-Ulecia, Karel
    One of the problems that most affect humanity today is the wastewater discharge into different water bodies. It was estimated that more than 7 million tons of wastewater are generated worldwide and are discharged into rivers, lakes, and reservoirs. Among the most dangerous wastewaters are those from inorganic chemistry research laboratories, mainly due to heavy metals. These problems have become a highly relevant topic, and numerous researchers have tried to design wastewater treatment systems that will deal more efficiently with heavy metals elimination. In this work, the synthesis, characterization, and evaluation of hydrated aluminium silicate were performed as alternative wastewater treatment from chemistry research and teaching laboratories. The compound obtained was Al_2O_33SiO_2H_2O, which was characterized by the determination of its physicochemical properties. These revealed a low density, very porous material, with low crystallinity, strong chemical resistance, a large surface area, and a high apparent ionic exchange capacity. Absorption kinetics studies of heavy metals in aqueous solutions, through more widespread models, have demonstrated that Al_2O_33SiO_2H_2O has excellent properties as absorbents of this material. The amorphous hydrated aluminium silicate achieves a decrease in the concentration of all the metal ions studied, reducing them to discharge levels permissible.
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    Study of the affinity between the protein kinase PKA and peptide substrates derived from kemptide using molecular dynamics simulations and MM/GBSA
    (Public Library of Science, 2014) Mena-Ulecia, Karel; Vergara-Jaque, Ariela; Poblete, Horacio; Tiznado, William; Caballero, Julio
    We have carried out a protocol in computational biochemistry including molecular dynamics (MD) simulations and MM/GBSA free energy calculations on the complex between the protein kinase A (PKA) and the specific peptide substrate Kemptide (LRRASLG). We made the same calculations on other PKA complexes that contain Kemptide derivatives (with mutations of the arginines, and with deletions of N and C-terminal amino acids). We predicted shifts in the free energy changes from the free PKA to PKA-substrate complex (δδGE→ES) when Kemptide structure is modified (we consider that the calculated shifts correlate with the experimental shifts of the free energy changes from the free PKA to the transition states (δδGE→TS) determined by the catalytic efficiency (kcat/KM) changes). Our results demonstrate that it is possible to predict the kinetic properties of protein kinases using simple computational biochemistry methods. As an additional benefit, these methods give detailed molecular information that permit the analysis of the atomic forces that contribute to the affinity between protein kinases and their substrates. © 2014 Mena-Ulecia et al.