Browsing by Author "Forero Girón, Angie"

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    Complexation of AAPH (2,2′-azobis(2-methylpropionamidine) dihydrochloride) with cucurbit[7]uril enhances the yield of AAPH-derived radicals
    (2023) Forero Girón, Angie; Fuentealba Patiño, Denis Alberto; Mariño Ocampo, Nory Johana; Gutiérrez Oliva, Soledad; Herrera Pisani, Bárbara Andrea; Toro Labbé, Alejandro; Fuentes Lemus, Eduardo; Davies, Michael J.; Aliaga Miranda, Margarita Elly; López Alarcón, Camilo Ignacio
    AAPH (2,2′-azobis(2-methylpropionamidine) dihydrochloride), a water-soluble azo compound is widely employed to produce peroxyl radicals for chemical and biological studies. This compound is shown herein to form a stable inclusion complex with cucurbit[7]uril (CB7), a well-established supramolecular host. Competitive binding assays using berberine dye, isothermal titration calorimetry (ITC), and nuclear magnetic resonance (1H-NMR) experiments, provided evidence for the inclusion of AAPH inside the CB7 cavity with a binding constant of 2.5 ± 0.8 x 105 L mol-1 (determined by ITC). Computational analysis at B3LYP-D3BJ/6-311G(d,p) of the complex (AAPH@CB7) showed interactions of the positively-charged amino groups of AAPH with carbonyl functions at the CB7 entrances. Photolysis of AAPH@CB7 by illumination at 365 nm, gave a higher yield of carbon-centered radicals when compared to the absence of CB7, as evidenced by electron paramagnetic resonance spin trapping using α-phenyl-N-t-butylnitrone. Enhanced radical formation was corroborated by increased consumption of pyrogallol red, free Trp and Trp-containing peptides when these were exposed to AAPH@CB7 in the presence of light. The increased yield of radicals generated by AAPH@CB7 is believed to arise from a pull effect of CB7 portals on initial AAPH-derived carbon-centered radicals generated by photolysis. It is proposed that these radicals are exposed and released to the bulk solution and react with O2 to give peroxyl radicals. These results suggest that the AAPH@CB7 complex can be used to generate high yields of peroxyl radicals for their use in studying these species in material, environmental and biomedical sciences amongst others.
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    Complexes between 2,20-azobis(2methylpropionamidine) dihydrochloride (AAPH) and cucurbit[n]uril hosts modulate the yield and fate of photolytically-generated AAPH radicals
    (Royal Society of Chemistry, 2024) Forero Girón, Angie; Oyarzún Alfaro, Mauricio Sebastián; Droguett Muñoz, Kevin Arturo; Fuentealba Patiño, Denis Alberto; Gutiérrez Oliva, Soledad; Herrera Pisani, Bárbara Andrea; Toro Labbé, Alejandro; Fuentes Lemus, Eduardo Felipe; Davies, Michael J.; López Alarcón, Camilo Ignacio; Aliaga Miranda, Margarita Elly
    Using theoretical and experimental tools we investigated the recognition of AAPH (2,2′-azobis(2-methylpropionamidine) dihydrochloride), a well-known water-soluble azo-compound employed as a source of peroxyl radicals, by cucurbit[6]uril (CB[6]), and cucurbit[8]uril (CB[8]). Density functional theory calculations and isothermal titration calorimetry experiments demonstrated that AAPH was not included in the cavity of CB[6], however, an exclusion complex was generated. Inclusion of AAPH in the CB[8] cavity was favored, forming stable inclusion complexes at 1 : 1 and 2 : 1 stoichiometries; AAPH@CB[8] and 2AAPH@CB[8], respectively. Radical formation upon photolytic cleavage of AAPH was examined theoretically, and by spin trapping with electron paramagnetic resonance. The radical yields detected with uncomplexed (free) AAPH and the AAPH-CB[6] (exclusion) complex were identical, whereas a marked decrease was shown for AAPH@CB[8]. Lower decreases were seen with a bimolecular (2 : 1) AAPH-CB[8] inclusion complex (2AAPH@CB[8]). This modulation was corroborated by the consumption of pyrogallol red (PGR), an oxidizable dye that does not associate with CB[6] or CB[8]. AAPH-CB[6] and 2AAPH@CB[8] did not significantly modify the initial consumption rate (Ri) of PGR, whereas AAPH@CB[8] decreased this. The oxidative consumption of free Trp, Gly-Trp and Trp-Gly by radicals derived from AAPH in the presence of CB[8] showed a dependence on the association of the targets with CB[8].
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    Computational study of the supramolecular complexation of azocompounds with cucurbit[7]uril: effects on the production and release of free radicals
    (Springer Science and Business Media Deutschland GmbH, 2024) Forero Girón, Angie; Gutiérrez Oliva, Soledad; López Alarcón, Camilo Ignacio; Herrera Pisani, Bárbara Andrea; Aliaga Miranda, Margarita Elly
    Context: An inclusion complex between 2,2′-azobis(2-methylpropionamidine) dihydrochloride (AAPH), a widely employed azocompound, and cucurbit[7]util (CB[7]), has shown an increased yield of radicals derived from the homolytic cleavage of the azo bond. Aimed to get insights about the formation of complexes and their effect on the yield of radicals production, complexes of CB[7] with seven azocompounds were studied by computational methods. Molecular electrostatic surfaces and structural analysis showed that the inclusion of symmetrical azocompounds inside of CB[7] depends mainly on the charge density and position of the functional groups at the main chain of the azoderivative. Analysis of non-covalent interactions and thermodynamic outcomes revealed that positively charged azocompounds with amidinium or imidazolium groups presented strong favorable interactions (multiple hydrogen bonds) with the oxygens of CB[7] portals. Additionally, carbon-centered radicals generated from the complexes (azocompounds@CB[7]) were corroborated using the electron localization function (ELF). Results evidenced that the strength of the interactions and the level of inclusion (partial or complete) between the azocompound and CB[7] determined the final orientation of the radicals (located out- or inside of the CB[7] cavity). Obtained results could be employed to design new supramolecular systems based on the properties of azocomplound@CB[7] complexes for new scientific or industrial applications. Methods: First-principles calculations at B3LYP-D3BJ/6-311g(d,p) level theory in the gas phase and in solvent (PCM, water) were performed in Gaussian 16 software package. The dispersion energy correction was included through the Grimme’s dispersion with Becke-Johnson damping D3(BJ). Thermodynamical data and the minimum character of all structures were obtained from vibrational frequency calculations. NBO, Multiwfn, Chemcraft, and NCIPLOT software were used to perform population analysis, analyze outcomes, visualize data, and display non-covalent interactions respectively.
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    How does dopamine convert into norepinephrine? Insights on the key step of the reaction
    (SPRINGER, 2025) Forero Girón, Angie; Toro Labbe, Alejandro
    Context Dopamine beta-monooxygenase (D beta M) is an essential enzyme in the organism that regioselectively converts dopamine into R-norepinephrine, the key step of the reaction, studied in this paper, is a hydrogen atom transfer (HAT) from dopamine to a superoxo complex on D beta M, forming a hydroperoxo intermediate and dopamine radical. It was found that the formation of a hydrogen bond between dopamine and the D beta M catalyst strengthens the substrate-enzyme interaction and facilitates the HAT which takes place selectively to give the desired enantiomeric form of the product. Six reactions leading to the hydroperoxo intermediate were analyzed in detail using theoretical and computational tools in order to identify the most probable reaction mechanism. The reaction force analysis has been used to demonstrate that the nature of the activation energy is mostly structural and largely due to the initial approach of species in order to get closer to each other to facilitate the hydrogen abstraction. On the other hand, the reaction electronic flux revealed that electronic activity driving the reactions is triggered by polarization effects and, in the most probable reaction among the six studied, it takes place in a concerted and non-spontaneous way. Chemical events driving the reaction have been identified and the energy absorbed or delivered by each one was quantified in detail. Methods The dopamine and a computational model of the copper superoxo complex on D beta M were optimized at B3LYP-D3(BJ)/6-311 G(d,p) level theory in the Gaussian 16 software package. Optimization and IRC calculations were performed in the gas phase and through the PCM solvation model to mimic the protein medium. Non-covalent interactions were plotted using the NCI-plot software.