Examinando por Autor "Fuentealba, Denis"
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Ítem Direct Oral FXa Inhibitors Binding to Human Serum Albumin: Spectroscopic, Calorimetric, and Computational Studies(MDPI, 2023-03) Mariño-Ocampo, Nory; F. Rodríguez, Diego; Guerra Díaz, Daniel; Zúñiga-Núñez, Daniel; Duarte, Yorley; Fuentealba, Denis; C. Zacconi, FlaviaDirect 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 in blood plasma, is a key research area and provides crucial information about drugs’ pharmacokinetics and pharmacodynamic properties. This research focuses on the study of the interactions between HSA and four commercially available direct oral FXa inhibitors, applying methodologies including steady-state and time-resolved fluorescence, isothermal titration calorimetry (ITC), and molecular dynamics. The HSA complexation of FXa inhibitors was found to occur via static quenching, and the complex formation in the ground states affects the fluorescence of HSA, with a moderate binding constant 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 suspected binding mode is supported by molecular dynamics simulations, where the predominant interactions were hydrogen bonds and hydrophobic interactions (mainly π–π stacking interactions between the phenyl ring of FXa inhibitors and the indole moiety of Trp214). Finally, the possible implications of the obtained results regarding pathologies such as hypoalbuminemia are briefly discussed. © 2023 by the authors.Ítem Fatty Acid Conjugates of Toluidine Blue O as Amphiphilic Photosensitizers: Synthesis, Solubility, Photophysics and Photochemical Properties(Blackwell Publishing Inc., 2021-01) Robinson-Duggon, José; Pizarro, Nancy; Gunther, Germán; Zúñiga-Núñez, Daniel; Edwards, Ana María; Greer, Alexander; Fuentealba, DenisToluidine blue O (TBO) is a water-soluble photosensitizer that has been used in photodynamic antimicrobial and anticancer treatments, but suffers from limited solubility in hydrophobic media. In an effort to incrementally increase TBO’s hydrophobicity, we describe the synthesis of hexanoic (TBOC6) and myristic (TBOC14) fatty acid derivatives of TBO formed in low to moderate percent yields by condensation with the free amine site. Covalently linking 6 and 14 carbon chains led to modifications of not only TBO’s solubility, but also its photophysical and photochemical properties. TBOC6 and TBOC14 derivatives were more soluble in organic solvents and showed hypsochromic shifts in their absorption and emission bands. The solubility in phosphate buffer solution was low for both TBOC6 and TBOC14, but unexpectedly slightly greater in the latter. Both TBOC6 and TBOC14 showed decreased triplet excited-state lifetimes and singlet oxygen quantum yields in acetonitrile, which was attributed to heightened aggregation of these conjugates particularly at high concentrations due to the hydrophobic “tails.” While in diluted aqueous buffer solution, indirect measurements showed similar efficiency in singlet oxygen generation for TBOC14 compared to TBO. This work demonstrates a facile synthesis of fatty acid TBO derivatives leading to amphiphilic compounds with a delocalized cationic “head” group and hydrophobic “tails” for potential to accumulate into biological membranes or membrane/aqueous interfaces in PDT applications.Ítem New Light-Green Thermally Activated Delayed Fluorescence Polymer Based on Dimethylacridine-Triphenyltriazine Light-Emitting Unit and Tetraphenylsilane Moiety as Non-Conjugated Backbone(MDPI, 2023-01) Hauyon, René A.; Fuentealba, Denis; Pizarro, Nancy; Ortega-Alfaro, María C.; Ugalde-Saldívar, Víctor M.; Sobarzo, Patricio A.; Medina, Jean; García, Luis; Jessop, Ignacio A.; González-Henríquez, Carmen M.; Tundidor-Camba, Alain; Terraza, Claudio A.In the search for solution-processable TADF materials as a light emitting layer for OLED devices, polymers have attracted considerable attention due to their better thermal and morphological properties in the film state with respect to small molecules. In this work, a new polymer (p-TPS-DMAC-TRZ) with thermally activated delayed fluorescence (TADF) light-emitting characteristics was prepared from a conjugation-break unit (TPS) and a well-known TADF core (DAMC-TRZ). This material was designed to preserve the photophysical properties of DAMC-TRZ, while improving other properties, such as thermal stability, promoted by its polymerization with a TPS core. Along with excellent solubility in common organic solvents such as toluene, chloroform and THF, the polymer (Mn = 9500; Mw = 15200) showed high thermal stability (TDT5% = 481 °C), and a Tg value of 265 °C, parameters higher than the reference small molecule DMAC-TRZ (TDT5% = 305 °C; Tg = 91 °C). The photoluminescence maximum of the polymer was centered at 508 nm in the solid state, showing a low redshift compared to DMAC-TRZ (500 nm), while also showing a redshift in solution with solvents of increasing polarity. Time-resolved photoluminescence of p-TPS-DMAC-TRZ at 298 K, showed considerable delayed emission in solid state, with two relatively long lifetimes, 0.290 s (0.14) and 2.06 s (0.50), and a short lifetime of 23.6 ns, while at 77 K, the delayed emission was considerably quenched, and two lifetimes in total were observed, 24.6 ns (0.80) and 180 ns (0.20), which was expected from the slower RISC process at lower temperatures, decreasing the efficiency of the delayed emission and demonstrating that p-TPS-DMAC-TRZ has a TADF emission. This is in agreement with room temperature TRPL measurements in solution, where a decrease in both lifetime and delayed contribution to total photoluminescence was observed when oxygen was present. The PLQY of the mCP blend films with 1% p-TPS-DMAC-DMAC-TRZ as a dopant was determined to be equal to 0.62, while in the pure film, it was equal to 0.29, which is lower than that observed for DMAC-TRZ (0.81). Cyclic voltammetry experiments showed similarities between p-TPS-DMAC-TRZ and DAMC-TRZ with HOMO and LUMO energies of −5.14 eV and −2.76 eV, respectively, establishing an electrochemical bandgap value of 2.38 eV. The thin film morphology of p-TPS-DMAC-TRZ and DMAC-TRZ was compared by AFM and FE-SEM, and the results showed that p-TPS-DMAC-TRZ has a smoother surface with fewer defects, such as aggregations. These results show that the design strategy succeeded in improving the thermal and morphological properties in the polymeric material compared to the reference small molecule, while the photophysical properties were mostly maintained, except for the PLQY determined in the pure films. Still, these results show that p-TPS-DMAC-TRZ is a good candidate for use as a light-emitting layer in OLED devices, especially when used as a host-guest mixture in suitable materials such as mCP. © 2022 by the authors.