Modelling the hydrolysis of succinimide:: formation of aspartate and reversible isomerization of aspartic acid via 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 DeltaHdegrees and DeltaSdegrees 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.