No abstract

The hydrolysis of a succinimide derivative in alkali and neutral media has been studied at the B3LYP/6-31+G* level. Stepwise and concerted mechanisms have been considered in a vacuum. Both mechanisms have been also studied in solution by means of integral equation formalism-polarizable continuum model with a single point calculation. In basic medium, the stepwise mechanism consists of a bond cleavage and a subsequent rotation of the hydroxyl group that require 8.6 and 3.0 kcal/mol, respectively. For the concerted hydrolysis in the same medium, the barrier is 9.8 kcal/mol. In neutral medium, the hydrolysis is facilitated by the presence of a polar continuum, whereas in basic medium, the polar environment hinders hydrolysis of succinimide.

In the present study, we have modelled the nucleophilic attack of water and a hydroxyl anion on the carbonyl carbon of a succinimide derivative leading to aspartate and aspartic acid. Calculations have been carried out at the B3LYP/6-31 +G* level in a vacuum. The IEF-PCM methodology has been used to carry out single point calculations in solution. In neutral medium, hydrolysis is facilitated by the presence of a polar continuum, whereas in basic medium the polar environment hinders the hydrolysis of succinimide. The deltaH degrees and deltaS degrees values for the cyclization reactions of aspartic acid yielding succinimide are 29.2 kJ mol(-1) and 133.5 kJ mol(-1) K(-1) respectively in accordance with the experimental results on the isomerization of the Ac-Asp-Gly-NHMe dipeptide unit. In a neutral medium, the isoaspartate: aspartate is found to be 2.2:1 in a vacuum and 3.4:1 in solution, in line with the experimental findings based on the hydrolysis of a tetrapeptide (Ac-Gly-Asn-Gly-Gly-NHMe) and a hexapeptide (Val-Tyr-Pro-Asn-Gly-Ala) where this ratio was found to be 3.1:1.