Browsing by Author "Rodríguez Sánchez, Diego Fernando"

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    Bio-click chemistry: a bridge between biocatalysis and click chemistry
    (2022) Rodríguez Sánchez, Diego Fernando; Moglie, Yanina; Ramírez Sarmiento, César Antonio; Singh, Sachin Kumar; Dua, Kamal; Zacconi, Flavia C. M.
    The fields of click chemistry and biocatalysis have rapidly grown over the last two decades. The development of robust and active biocatalysts and the widespread use of straightforward click reactions led to significant interactions between these two fields. Therefore the name bio-click chemistry seems to be an accurate definition of chemoenzymatic reactions cooperating with click transformations. Bio-click chemistry can be understood as the approach towards molecules of high-value using a green and sustainable approach by exploiting the potential of biocatalytic enzyme activity combined with the reliable nature of click reactions. This review summarizes the principal bio-click chemistry reactions reported over the last two decades, with a special emphasis on small molecules. Contributions to the field of bio-click chemistry are manifold, but the synthesis of chiral molecules with applications in medicinal chemistry and sustainable syntheses will be especially highlighted.
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    Direct Oral FXa Inhibitors Binding to Human Serum Albumin: Spectroscopic, Calorimetric, and Computational Studies
    (2023) Mariño Ocampo, Nory Johana; Rodríguez Sánchez, Diego Fernando; Daniel Sebastian, Guerra Diaz; Zúñiga Núñez, Daniel; Duarte, Yorley; Fuentealba Patiño, Denis Alberto; Zacconi, Flavia C. M.
    Direct FXa inhibitors are an important class of bioactive molecules (rivaroxaban, apixaban,edoxaban, and betrixaban) applied for thromboprophylaxis in diverse cardiovascular pathologies.The interaction of active compounds with human serum albumin (HSA), the most abundant protein inblood plasma, is a key research area and provides crucial information about drugs’ pharmacokineticsand pharmacodynamic properties. This research focuses on the study of the interactions betweenHSA and four commercially available direct oral FXa inhibitors, applying methodologies includingsteady-state and time-resolved fluorescence, isothermal titration calorimetry (ITC), and moleculardynamics. The HSA complexation of FXa inhibitors was found to occur via static quenching, and thecomplex formation in the ground states affects the fluorescence of HSA, with a moderate bindingconstant of 104 M−1. However, the ITC studies reported significantly different binding constants (103 M−1) compared with the results obtained through spectrophotometric methods. The suspectedbinding mode is supported by molecular dynamics simulations, where the predominant interactionswere hydrogen bonds and hydrophobic interactions (mainly π–π stacking interactions between thephenyl ring of FXa inhibitors and the indole moiety of Trp214). Finally, the possible implications ofthe obtained results regarding pathologies such as hypoalbuminemia are briefly discussed.
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    Novel Combi-lipase Systems for Fatty Acid Ethyl Esters Production
    (2019) Toro, E.C.; Rodríguez Sánchez, Diego Fernando; Morales, N.; Garcia, L.M.; Godoy, C.A.
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    Substitution Effects in Aryl Halides and Amides into the Reaction Mechanism of Ullmann-Type Coupling Reactions
    (2024) Durán, Rocío; Barrales Martínez, César; Santana Romo, Fabián Mauricio; Rodríguez Sánchez, Diego Fernando; Zacconi, Flavia C. M.; Herrera Pisani, Bárbara Andrea
    In this article, we present a comprehensive computational investigation into the reaction mechanism of N-arylation of substituted aryl halides through Ullmann-type coupling reactions. Our computational findings, obtained through DFT ωB97X-D/6-311G(d,p) and ωB97X-D/LanL2DZ calculations, reveal a direct relation between the previously reported experimental reaction yields and the activation energy of haloarene activation, which constitutes the rate-limiting step in the overall coupling process. A detailed analysis of the reaction mechanism employing the Activation Strain Model indicates that the strain in the substituted iodoanilines is the primary contributor to the energy barrier, representing an average of 80% of the total strain energy. Additional analysis based on conceptual Density Functional Theory (DFT) suggests that the nucleophilicity of the nitrogen in the lactam is directly linked to the activation energies. These results provide valuable insights into the factors influencing energetic barriers and, consequently, reaction yields. These insights enable the rational modification of reactants to optimize the N-arylation process.