A Detailed Computational Study of n-Acetylglutamate Hydrolysis under Acidic and Basic Conditions

Aims: N-acetylglutamate (NAG) is the first intermediate in the arginine biosynthetic pathway in
prokaryotes, eukaryotes, and lower plants. The hydrolysis of amides is very important in biochemistry
as a model for bond cleavage in living systems and has been studied experimentally and in theory to
study N-acetylglutamate hydrolysis under acidic and basic conditions, using molecular modeling
techniques.
Study Design: Hydrolysis of N-acetylglutamate was studied under acidic and basic conditions to
establish the differences in chemical properties and conditions of favorability; this was performed
using the Mulliken charges and the geometric parameters as descriptors, as well as proton affinity,
Gibbs free energy, and equilibrium constants.
Place and Duration of Study: Grupo de Investigación Max Planck, Facultad de Química y Farmacia,
Universidad del Atlántico, between February 2014 and March 2015.
Methodology: Structures of the hydrolysis reaction under acidic and basic conditions were optimized
using molecular mechanics prior to calculating various molecular descriptors. The Hartree–Fock (HF)
method was used with the 3-21G and 6-31G* basis sets. Some useful parameters for analyzing the
reactions are proton affinity, Frontier Molecular Orbitals, Gibbs free energy, and equilibrium constants.
Results: In general, reaction profiles demonstrated that the two reactions are favorable; however, in
agreement with our preliminary equilibrium constant findings, a greater favorability for basic hydrolysis
was shown.
Conclusion: By analyzing the calculated values for the Gibbs free energy, it was observed that the
NAG hydrolysis under basic conditions is more favorable. The calculated equilibrium constants are in
agreement with the favorability of hydrolysis under basic conditions, which is consistent with the
biochemical process.