Browsing by Author "Campodonico, Paola R."

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    Betaine-urea deep eutectic solvent improves imipenem antibiotic activity
    (2022) Olivares, Belen; Martinez, Fabian A.; Ezquer, Marcelo; Morales, Bernardo J.; Fuentes, Ignacia; Calvo, Margarita; Campodonico, Paola R.
    Beta-lactam antibiotics are highly unstable in aqueous media, which may lead to subclinical concentrations, antimicrobial resistance and therapeutic failure. In previous work we demonstrated that a natural deep eutectic solvent consisting of betaine and urea (BU) is capable of improving the stability of some beta-lactams, including imipenem (IMP), the most unstable antibiotic of the family. Here, IMP-BU was studied by selective protonic Nuclear Overhauser Effect Spectroscopy Magnetic Resonance (H-1 NOESY NMR) to gain insight into the mechanism by which BU protects IMP. The kinetics of IMP release and its antibacterial activity were evaluated in diffusional, time-kill and antibiofilm assays. It was found that BU is a protective matrix which allows a fast release of IMP, resulting in superior antibacterial activity when compared to IMP in aqueous solution, both against bacteria growing in planktonic form and in biofilms. Furthermore, it was shown that BU is nontoxic when evaluated in fibroblast primary cell cultures and in organotypic skin cultures, and is not immunogenic when tested in vitro in macrophage cultures, suggesting that BU has potential application as a biomaterial or excipient. (C) 2022 Published by Elsevier B.V.
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    Experimental Analyses Emphasize the Stability of the Meisenheimer Complex in a SNAr Reaction Toward Trends in Reaction Pathways
    (2020) Campodonico, Paola R.; Olivares, Belen; Tapia, Ricardo A.
    The mechanism of SNAr reactions between 2-chloro-5-nitropyrimidine with primary and secondary alicyclic amines, respectively, have been studied by kinetic measurements. The kinetic data obtained in aqueous media opens a controversial discussion based on Bronsted-type plots analysis. The first approach based on the kinetic data reveals a non-catalyzed pathway. Then, the subtlety of the mathematical treatment of the kinetic data is discussed over a concerted or stepwise mechanism, respectively.
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    How the Nature of an Alpha-Nucleophile Determines a Bronsted Type-Plot and Its Reaction Pathways. An Experimental Study
    (2022) Campodonico, Paola R.; Tapia, Ricardo A.; Suarez-Rozas, Cristian
    The reactions between 2-chloro-5-nitro pyrimidine with a serie of alpha-nucleophile derivatives were kinetically evaluated. The kinetic study was carried out in aqueous media and the data shown an unusual split on the Bronsted type-plot, opening a controversial discussion based on reactivities and possible reaction pathways. These split Bronsted type-plots are discussed over the hypothetical transition state (TS) structures associated to concerted or stepwise mechanisms with emphasis on hydrogen bond interactions between electrophile/nucleophile pair able to determine the reactivities and the plausible reaction routes.