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Experimental Analyses Emphasize the Stability of the Meisenheimer Complex in a SNAr Reaction Toward Trends in Reaction Pathways

2020 , CAMPODONICO GALDAMES, PAOLA ROSSANA , OLIVARES, MARIA BELEN , Ricardo A. Tapia

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Chronic Voluntary Morphine Intake Is Associated with Changes in Brain Structures Involved in Drug Dependence in a Rat Model of Polydrug Use

2023 , María Elena Quintanilla , Paola Morales , Daniela Santapau , Alba Ávila , Carolina Ponce , BERRIOS CARCAMO, PABLO ANDRES , OLIVARES, MARIA BELEN , Mario Herrera-Marschitz , EZQUER, EDUARDO MARCELO , Javiera Gallardo , Yedy Israel , EZQUER, EDUARDO FERNANDO

Chronic opioid intake leads to several brain changes involved in the development of dependence, whereby an early hedonistic effect (liking) extends to the need to self-administer the drug (wanting), the latter being mostly a prefrontal–striatal function. The development of animal models for voluntary oral opioid intake represents an important tool for identifying the cellular and molecular alterations induced by chronic opioid use. Studies mainly in humans have shown that polydrug use and drug dependence are shared across various substances. We hypothesize that an animal bred for its alcohol preference would develop opioid dependence and further that this would be associated with the overt cortical abnormalities clinically described for opioid addicts. We show that Wistar-derived outbred UChB rats selected for their high alcohol preference additionally develop: (i) a preference for oral ingestion of morphine over water, resulting in morphine intake of 15 mg/kg/day; (ii) marked opioid dependence, as evidenced by the generation of strong withdrawal signs upon naloxone administration; (iii) prefrontal cortex alterations known to be associated with the loss of control over drug intake, namely, demyelination, axonal degeneration, and a reduction in glutamate transporter GLT-1 levels; and (iv) glial striatal neuroinflammation and brain oxidative stress, as previously reported for chronic alcohol and chronic nicotine use. These findings underline the relevance of polydrug animal models and their potential in the study of the wide spectrum of brain alterations induced by chronic morphine intake. This study should be valuable for future evaluations of therapeutic approaches for this devastating condition.

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A Natural Deep Eutectic Solvent Formulated to Stabilize beta-Lactam Antibiotics

2018 , OLIVARES, MARIA BELEN , Fabián Martínez , RIVAS JIMENEZ, LINA MARIA , Cristian Calderón , MUNITA SEPULVEDA, JOSE MANUEL , CAMPODONICO GALDAMES, PAOLA ROSSANA

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Kinetics and Reaction Mechanism of Biothiols Involved in SNAr Reactions: An Experimental Study

2022 , CAMPODONICO GALDAMES, PAOLA ROSSANA , Jazmín Alarcón-Espósito , OLIVARES, MARIA BELEN

Few kinetic parameters, or reaction rates, are known up to date in detail about 1-chloro and 1-fluoro-2,4-dinitrobenzene (ClDNB and FDNB, respectively) with a series of biothiols in aqueous media. These biological nucleophiles with thiol groups have been widely used as a reference in nucleophile reactivity assays due to their prevalence and cellular abundance. The main aim of this study was to elucidate the reaction mechanism based on Brönsted-type plots and reactivity patterns of the electrophile/nucleophile pairs. A complete kinetic study was performed in terms of the comparison of Brönsted-type slope parameters (βnuc) for the reactions and was used for assigning the mechanism and the rate-determining step associated with the reaction route. A mass spectrometry analysis demonstrated that the nucleophilic center of the biothiols is the -SH group and there is only one kinetic product. The kinetic study suggests that the reaction mechanism might be the borderline between concerted and stepwise pathways. An amine–enol equilibrium for the most reactive nucleophiles appears to be the main determining factor controlling the nucleophilic attack in the nucleophilic aromatic substitution reactions investigated, highlighting the anionic form for these nucleophiles. This amine–enol equilibrium involves a hydrogen bond which stabilizes the intermediate species in the reaction pathway. Thus, intramolecular bonds are formed and enhance the nucleophilic strength through the contribution of the solvent surrounding the electrophile/nucleophile pairs. Finally, we highlight the importance of the formation of electrophile/nucleophile adducts that could modify structures and/or functions of biological systems with potential toxic effects. Therefore, it is essential to know all these kinetic and reactivity patterns and their incidence on other studies.

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Aloe vera peel-derived nanovesicles display anti-inflammatory properties and prevent myofibroblast differentiation

2024 , RAMIREZ PRADA, ORLANDO JOSUÉ , Florencia Pomareda , OLIVARES, MARIA BELEN , HUANG, YA LIN , Gabriela Zavala , Javiera Carrasco-Rojas , Simón Alvarez , Camila Leiva-Sabadini , Valeria Hidalgo , Pablo Romo , SANCHEZ JIMÉNEZ, MATÍAS IGNACIO , Ayleen Vargas , Sebastian Aguayo , SCHUH, CHRISTINA , MARTINEZ ARENAS, JESSICA ISABEL

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N-Acetylcysteine and Acetylsalicylic Acid Inhibit Alcohol Consumption by Different Mechanisms: Combined Protection

2020 , María Elena Quintanilla , EZQUER, EDUARDO FERNANDO , Paola Morales , EZQUER, EDUARDO MARCELO , OLIVARES, MARIA BELEN , Mario Herrera-Marschitz , Daniela Santapau , Yedy Israel

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Exploring the behavior of Candida antarctica lipase B in aqueous mixtures of an imidazolium ionic liquid and its surfactant analogue

2023 , CAMPODONICO GALDAMES, PAOLA ROSSANA , Cristian Calderón , Jackson J. Alcázar , OLIVARES, MARIA BELEN , Limberg Jaldin , Cristian Suárez-Rozas

The performance of Candida antarctica lipase B (CALB) has been evaluated in 1-butyl-3-methylimidazolium tetrafluoroborate (BMIMBF4)/water mixtures in a wide range of molar fractions (χBMIMBF4) with and without 1-dodecyl-3-methylimidazolium tetrafluoroborate (C12-MIMBF4), a surfactant derived from BMIMBF4. The main aim of this work is to evaluate the influence of χBMIMBF4 over micellar aggregates to assess the activity of enzymatic reactions. The investigated reaction corresponds to the hydrolysis of the substrate p-nitrophenyl laureate in each χBMIMBF4. The kinetic study for χBMIMBF4 at around 0.2 proved to be a border point in enzymatic activity. At χBMIMBF4 = 0.1, the lipase activity increases in the presence of C12-MIMBF4. However, at higher concentrations, BMIMBF4 has a negligible effect over the lipase activity. These results suggest specific interactions between water and BMIMBF4 molecules in relation to CALB. This research highlights the superactivity phenomenon driven by the reaction media and the micelle interface. In this interfacial interaction, BMIMBF4 acts directly on the changes induced on the enzyme upon its interaction with the micellar interface. This study opens a green perspective toward the biocatalysis field.

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Material Suplementario - Kinetics and Reaction Mechanism of Biothiols Involved in SNAr Reactions: An Experimental Study

2022 , CAMPODONICO GALDAMES, PAOLA ROSSANA , OLIVARES, MARIA BELEN

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Aspirin and N‐acetylcysteine co‐administration markedly inhibit chronic ethanol intake and block relapse binge drinking: Role of neuroinflammation‐oxidative stress self‐perpetuation

2019 , Yedy Israel , María Elena Quintanilla , EZQUER, EDUARDO FERNANDO , Paola Morales , Daniela Santapau , BERRIOS CARCAMO, PABLO ANDRES , EZQUER, EDUARDO MARCELO , OLIVARES, MARIA BELEN , Mario Herrera‐Marschitz

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Betaine-urea deep eutectic solvent improves imipenem antibiotic activity

2022 , OLIVARES, MARIA BELEN , Fabián A. Martínez , Bernardo J. Morales , EZQUER, EDUARDO MARCELO , Margarita Calvo , FUENTES BUSTOS, MARIA IGNACIA , CAMPODONICO GALDAMES, PAOLA ROSSANA