Catalytic Role of Vicinal OH in Ester Aminolysis: Proton Shuttle versus Hydrogen Bond Stabilization

This computational study provoked by the process of peptide bond formation in the ribosome investigates the influence of the vicinal OH group in monoacylated diols on the elementary acts of ester aminolysis Two alternative approaches I or this influence on ester ammonolysis were considered stabilization of the transition states by hydrogen bonds and participation of the vicinal hydroxyl in proton transfer (proton shuttle) Hie activation due to hydrogen bonds of the victual hydroxyl via tetragonal transition states was rather modest. the free energy of activation was reduced by only 5 2 kcal/mol compared to the noncatalyzed react ion The catalytic activation via the pinion shuttle mechanism with participation of the vicinal OH in the proton transfer via hexagonal transition states resulted in considerable reduction of the free energy of activation to 33.5 kcal/mol i.e. 16 0 kcal/mol lower than in the referent process Accounting in, the influence of the environment on the reaction center by a continuum model (for r from Sin 80) resulted in further stabilization of the late-determining transition state by 4-5 kcal/mol The overall reduction of the reaction bait by about 16 kcal/mol as compared to the noncatalyzed process corresponds to about 10(9)-fold acceleration of the reaction, in agreement with the experimental estimate I or acceleration ()I this process in the ribosome