A computational study of the reaction mechanism involved in the fast cleavage of an unconstrained amide bond assisted by an amine intramolecular nucleophilic attack.
J Comput Chem
; 42(12): 818-826, 2021 05 05.
Article
em En
| MEDLINE
| ID: mdl-33590912
In the present work, the fast amide bond cleavage of [3-((1R,5S,7s)-3-azabicyclo[3.3.1]nonane-7-carbonyl)-3-azabicyclo[3.3.1]nonane-7-carboxylic acid (bi-ATDO)], through an intramolecular nucleophilic attack of an amine group is evaluated. First, six possible peptide bond cleavage mechanisms, two of them including a water molecule, are described at the ωB97XD/6-311 + G(d,p)//MP2/6-311 + G(d,p) level of theory. The reaction consisting of an intramolecular nitrogen nucleophilic attack followed by a proton transfer and the amide bond cleavage is determined as the most favorable mechanism. The activation free energy computed for the latter is 20.5 kcal mol-1 , which agrees with the reported experimental result of 24.8 kcal mol-1 . Inclusion of a water molecule to assist the first step of the reaction results in an activation free energy increase of about 17 kcal mol-1 . All the steps in the most favorable mechanism are studied more in detail employing intrinsic reaction coordinate as well as the reaction force and reaction electronic flux analysis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
J Comput Chem
Assunto da revista:
QUIMICA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Equador
País de publicação:
Estados Unidos