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

• Published in: Journal of organic chemistry Vol. 75; no. 20; pp. 6782 - 6792
• Main Authors: Rangelov, Miroslav A, Petrova, Galina P, Yomtova, Vihra M, Vayssilov, Georgi N
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 15.10.2010
• Subjects: Ammonia - chemistry; Catalysis; Chemistry; Esters - chemistry; Exact sciences and technology; Glucosides - chemistry; Hydrogen Bonding; Hydroxides - chemistry; Kinetics and mechanisms; Molecular Conformation; Molecular Dynamics Simulation; Organic chemistry; Peptides; Preparations and properties; Protons; Pyrimidinones - chemistry; Reactivity and mechanisms; Thermodynamics; Water - chemistry; Diol; Catalytic reaction; Ribosome; Peptides; Reaction center; Peptide bond; Stabilization; Proton transfer; Theoretical study; Experimental study; Reaction rate; Energy barrier; Free energy; Chemical reduction; Ester; Hexagonal crystals; Aminolysis; Transition state; Reaction mechanism; Activation energy; Ammonolysis; Hydrogen bond
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo100886p

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 for 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). The activation due to hydrogen bonds of the vicinal 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 reaction. The catalytic activation via the proton 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 for the influence of the environment on the reaction center by a continuum model (for ε from 5 to 80) resulted in further stabilization of the rate-determining transition state by 4−5 kcal/mol. The overall reduction of the reaction barrier by about 16 kcal/mol as compared to the noncatalyzed process corresponds to about 109-fold acceleration of the reaction, in agreement with the experimental estimate for acceleration of this process in the ribosome.