Campodónico Paola R, Alarcón-Espósito Jazmín, Olivares Belén
Centro de Química Médica, Instituto de Ciencias e Innovación en Medicina, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Santiago, Chile.
Departamento de Química Orgánica y Fisicoquímica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.
Front Chem. 2022 Jun 8;10:854918. doi: 10.3389/fchem.2022.854918. eCollection 2022.
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 ( ) 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.
到目前为止，关于1-氯-2,4-二硝基苯和1-氟-2,4-二硝基苯（分别为ClDNB和FDNB）与一系列生物硫醇在水性介质中的动力学参数或反应速率，鲜少有详细报道。这些带有硫醇基团的生物亲核试剂因其普遍性和细胞丰度，已被广泛用作亲核试剂反应性测定的参考。本研究的主要目的是基于布朗斯特型曲线和亲电试剂/亲核试剂对的反应模式阐明反应机理。针对这些反应，通过比较布朗斯特型斜率参数（ ）进行了完整的动力学研究，并用于确定与反应途径相关的机理和速率决定步骤。质谱分析表明，生物硫醇的亲核中心是-SH基团，且只有一种动力学产物。动力学研究表明，反应机理可能处于协同和分步途径之间的边界。对于反应性最强的亲核试剂而言，胺-烯醇平衡似乎是控制所研究的亲核芳香取代反应中亲核进攻的主要决定因素，突出了这些亲核试剂的阴离子形式。这种胺-烯醇平衡涉及一个氢键，该氢键使反应途径中的中间物种稳定。因此，形成了分子内键，并通过围绕亲电试剂/亲核试剂对的溶剂的作用增强了亲核强度。最后，我们强调了亲电试剂/亲核试剂加合物形成的重要性，这些加合物可能会改变生物系统的结构和/或功能，并具有潜在毒性作用。因此了解所有这些动力学和反应模式及其在其他研究中的影响至关重要。
