Theoretical study on the alkaline and neutral hydrolysis of succinimide derivatives in deamidation reactions

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, res'pectively. 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.