title: Mechanistic insights into the dehalogenation reaction of fluoroacetate/fluoroacetic acid.
abstract: Fluoroacetate is a toxic compound whose environmental accumulation may represent an important contamination problem, its elimination is therefore a challenging issue. Fluoroacetate dehalogenase catalyzes its degradation through a two step process initiated by an S(N)2 reaction in which the aspartate residue performs a nucleophilic attack on the carbon bonded to the fluorine; the second step is hydrolysis that releases the product as glycolate. In this paper, we present a study based on density functional theory calculations of the S(N)2 initiation reaction modeled through the interaction between the substrate and the propionate anion as the nucleophile. Results are analyzed within the framework of the reaction force and using the reaction electronic flux to identify and characterize the electronic activity that drives the reaction. Our results reveal that the selective protonation of the substrate catalyzes the reaction by decreasing the resistance of the structural and electronic reorganization needed to reach the transition state. Finally, the reaction energy is modulated by the degree of stabilization of the fluoride anion formed after the S(N)2 reaction. In this way, a site-induced partial protonation acts as a chemical switch in a key process that determines the output of the reaction.
authors.affiliation: Chemical Processes and Catalysis (CPC), Departamento de Ciencias Químicas, Facultad de Ciencias Exactas, Universidad Andres Bello, Avenida República 275, Santiago, Chile.
authors.forename: Sebastián
authors.initials: S
authors.lastname: Miranda-Rojas
authors.affiliation: Laboratorio de Química Teórica Computacional (QTC), Facultad de Química, Pontificia Universidad Católica de Chile, Avenida Vicuña Mackenna 4860, Macul, Santiago, Chile.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Toro-Labbé