Browsing by Author "Toro Labbe, Alejandro"

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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.
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    Mechanisms of Formation of Hemiacetals: Intrinsic Reactivity Analysis
    (AMER CHEMICAL SOC, 2012) Azofra, Luis Miguel; Alkorta, Ibon; Elguero, Jose; Toro Labbe, Alejandro
    The reaction mechanism of the hemiacetal formation from formaldehyde and methanol has been studied theoretically at the B3LYP/6-311+ +G(d,p) level. In addition to the study of the reaction between the isolated reactants, three different kinds of catalysis have been explored. The first one examines the use of assistants, especially bridging water molecules, in the proton transfer process. The second one attempts to increase the local electrophilicity of the carbon atom in formaldehyde with the presence of a Bronsted acid (H+ or H3O+). The last one considers the combined effect of both catalytic strategies. The reaction force, the electronic chemical potential, and the reaction electronic flux have been characterized for the reaction path in each case. In general, it has been found that structural rearrangements represent an important energetic penalty during the activation process. The barriers for the reactions catalyzed by Bronsted acids show a high percentage of electronic reorganization contribution. The catalytic effects for the reactions assisted by water molecules are due to a reduction of the strain The reaction that includes both acid catalysis and proton assistance transfer shows the lowest in the transition state structures. energy barrier (25.0 kJ mol(-1)).
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    Understanding chemical binding using the Berlin function and the reaction force
    (ELSEVIER, 2012) Chakraborty, Debajit; Cardenas, Carlos; Echegaray, Eleonora; Toro Labbe, Alejandro; Ayers, Paul W.
    We use the derivative of the electron density with respect to the reaction coordinate, interpreted through the Berlin binding function, to identify portions of the reaction path where chemical bonds are breaking and forming. The results agree with the conventional description for S(N)2 reactions, but they are much more general and can be used to elucidate other types of reactions also. Our analysis offers support for, and detailed information about, the use of the reaction force profile to separate the reaction coordinates into intervals, each with characteristic extents of geometry change and electronic rearrangement. (C) 2012 Elsevier B.V. All rights reserved.
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    Understanding the Physics and Chemistry of Reaction Mechanisms from Atomic Contributions: A Reaction Force Perspective
    (AMER CHEMICAL SOC, 2012) Voehringer Martinez, Esteban; Toro Labbe, Alejandro
    Studying chemical reactions involves the knowledge of the reaction mechanism. Despite activation barriers describing the kinetics or reaction energies reflecting thermodynamic aspects, identifying the underlying physics and chemistry along the reaction path contributes essentially to the overall understanding of reaction mechanisms, especially for catalysis. In the past years the reaction force has evolved as a valuable tool to discern between structural changes and electrons' rearrangement in chemical reactions. It provides a framework to analyze chemical reactions and additionally a rational partition of activation and reaction energies. Here, we propose to separate these energies further in atomic contributions, which will shed new insights in the underlying reaction mechanism. As first case studies we analyze two intramolecular proton transfer reactions. Despite the atom based separation of activation barriers and reaction energies, we also assign the participation of each atom in structural changes or electrons' rearrangement along the intrinsic reaction coordinate. These participations allow us to identify the role of each atom in the two reactions and therfore the underlying chemistry. The knowledge of the reaction chemistry immediately leads us to suggest replacements with other atom types that would facilitate certain processes in the reaction. The characterization of the contribution of each atom to the reaction energetics, additionally, identifies the reactive center of a molecular system that unites the main atoms contributing to the potential energy change along the reaction path.