Kinetics and Reaction Mechanism of Biothiols Involved in SNAr Reactions: An Experimental Study
Journal
Frontiers in Chemistry
ISSN
2296-2646
Date Issued
2022
Type
Resource Types::text::journal::journal article
URL Institutional Repository
Abstract
<jats:p>Few kinetic parameters, or reaction rates, are known up to date in detail about 1-chloro and 1-fluoro-2,4-dinitrobenzene (ClDNB and FDNB, respectively) with a series of biothiols in aqueous media. These biological nucleophiles with thiol groups have been widely used as a reference in nucleophile reactivity assays due to their prevalence and cellular abundance. The main aim of this study was to elucidate the reaction mechanism based on Brönsted-type plots and reactivity patterns of the electrophile/nucleophile pairs. A complete kinetic study was performed in terms of the comparison of Brönsted-type slope parameters (<jats:italic>β</jats:italic><jats:sub>nuc</jats:sub>) for the reactions and was used for assigning the mechanism and the rate-determining step associated with the reaction route. A mass spectrometry analysis demonstrated that the nucleophilic center of the biothiols is the -SH group and there is only one kinetic product. The kinetic study suggests that the reaction mechanism might be the borderline between concerted and stepwise pathways. An amine–enol equilibrium for the most reactive nucleophiles appears to be the main determining factor controlling the nucleophilic attack in the nucleophilic aromatic substitution reactions investigated, highlighting the anionic form for these nucleophiles. This amine–enol equilibrium involves a hydrogen bond which stabilizes the intermediate species in the reaction pathway. Thus, intramolecular bonds are formed and enhance the nucleophilic strength through the contribution of the solvent surrounding the electrophile/nucleophile pairs. Finally, we highlight the importance of the formation of electrophile/nucleophile adducts that could modify structures and/or functions of biological systems with potential toxic effects. Therefore, it is essential to know all these kinetic and reactivity patterns and their incidence on other studies.</jats:p>
Cite this document
Campodónico, P. R., Alarcón-Espósito, J., & Olivares, B. (2022). Kinetics and reaction mechanism of biothiols involved in snar reactions: An experimental study. Frontiers in Chemistry, 10, 854918. https://doi.org/10.3389/fchem.2022.854918
Dataset(s)
Material Suplementario - Kinetics and Reaction Mechanism of Biothiols Involved in SNAr Reactions: An Experimental Study
Subjects
nucleophilic aromatic-substitution
;
secondary-amines
;
electronic theory
;
1-fluoro-2
;
4-dinitrobenzene
;
chemicals
;
solvents
;
thiols
;
aminolysis
;
principles
;
cysteine