Browsing by Author "Calderon, Cristian"
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Item A Natural Deep Eutectic Solvent Formulated to Stabilize β-Lactam Antibiotics(2018) Olivares, Belén; Martínez, Fabián; Rivas, Lina; Calderon, Cristian; Munita, José; Campodónico, Paolaβ-lactam antibiotics, such as penicillin share a very unstable chemical structure. In water-based solutions, such as those used for clinical applications, the β-lactam ring is readily opened due to a nucleophilic or electrophilic attack, leading to the loss of antimicrobial activity. Since the achievement and maintenance of optimum therapeutic levels of β-lactam antibiotics is critical for the resolution of many infectious clinical situations, and to avoid antibiotic resistance generation, the design of new non-aqueous dosage forms is urgent. Recently, natural deep eutectic solvents (NADES) have emerged as alternative non-toxic and non-aqueous solvents for different biomedical applications. In this work, we formulated and characterized a NADES composed by betaine and urea (BU). Using this solvent, we evaluated the stability of clavulanic acid (CLV) and imipenem (IMP) and characterized their antimicrobial activities calculating the minimal inhibitory concentration. Characterization of BU solvent by infrared spectroscopy (IR) and nuclear magnetic resonance spectroscopy (NMR) indicated that the obtained solvent has a microstructure mainly based on hydrogen bonding interactions and water addition strongly affects its dynamic. The stability of β-lactam antibiotic IMP and CLV using this solvent was increased by 7 fold and 2.5 fold respectively compared to water when analysed seven days after being dissolved. Microbiological assays showed that antibacterial activity at day seven was significantly decreased for both CLV and IMP when dissolved in water, while no change in their antibacterial properties was observed when antibiotics were dissolved in BU. The increased stability of IMP and CLV in BU may be related to the inert behaviour of the solvent and the higher dynamic restriction that helps antibiotics to maintain a more stable conformation. These data suggest the potential use of BU as a solvent to prevent degradation of β-lactam antibiotics.Item Activation of Electrophile/Nucleophile Pair by a Nucleophilic and Electrophilic Solvation in a SNAr Reaction(2018) Sánchez, Bruno; Calderon, Cristian; Tapia, Ricardo A.; Contreras, Renato; Campodónico, PaolaNucleophilic aromatic substitution reactions of 4-chloroquinazoline toward aniline and hydrazine were used as a model system to experimentally show that a substrate bearing heteroatoms on the aromatic ring as substituent is able to establish intramolecular hydrogen bond which may be activated by the reaction media and/or the nature of the nucleophile.Item The pore forming capacity of Sticholysin I in dipalmitoyl phosphatidyl vesicles is tuned by osmotic stress(Elsevier, 2017) Ahumada, Manuel; Calderon, Cristian; Lissi, E; Alvarez, Carlos; Lanio, MariaThe osmotic condition modulates the properties of liposomes, particularly those related to their stability and response to external agents such as membrane-active proteins or peptides. In a previous work, we have demonstrated that an osmotic shock can increase, per se, water influx/efflux and the exit of the fluorophore calcein entrapped in the aqueous pool of dipalmitoylphosphatidylcholine (DPPC) and DPPC:sphingomyelin (SM) large unilamellar vesicles (LUVs), suggesting a loss of integrity of the liposome bilayer. In the present work, we have extended our study in order to assess how an osmotic imbalance prior to or synchronous with the addition of a recombinant variant of the pore-forming toxin sticholysin I (rSt I) modifies its pore forming capacity in DPPC and DPPC:SM (1:1) LUVs. Our results conclusively show the capacity of hypotonic gradients to improve the pore forming capacity of rSt I molecules, even in pure DPPC liposomes, rendering pore-formation less dependent on the presence of sphyngomyelin. In fact, non-active toxins in DPPC liposomes become active by a hypotonic imbalance in a similar way to those containing SM as a second component.