Premium
Ab initio study of catalyzed and uncatalyzed amide bond formation as a model for peptide bond formation: Ammonia‐formic acid and ammonia‐glycine reactions
Author(s) -
Oie Tetsuro,
Loew Gilda H.,
Burt Stanley K.,
Binkley J. Stephen,
MacElroy Robert D.
Publication year - 2009
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.560220722
Subject(s) - chemistry , ab initio , formic acid , catalysis , computational chemistry , sn2 reaction , concerted reaction , transition state , reaction mechanism , ammonia , molecular orbital , molecule , stereochemistry , organic chemistry
As a model reaction for peptide bond formation, the S N 2 reactions between formic acid and ammonia (1) and between glycine and ammonia (2) have been studied with and without amine catalysis:\documentclass{article}\pagestyle{empty}\begin{document}$$ {\rm NH}_3 + {\rm HCOOH} + ({\rm NH}_3) \to {\rm NH}_{2} {\rm CHO + H}_{2} {\rm O + (NH}_{3} {\rm)}\quad \quad (1) $$\end{document}\documentclass{article}\pagestyle{empty}\begin{document}$$ {\rm NH}_3 + {\rm NH}_2 {\rm CH}_{2} {\rm COOH} + ({\rm NH}_3 ) \to {\rm NH}_{2} {\rm CH}_{2} {\rm CONH}_{2} {\rm + H}_{2} {\rm O + (NH}_{3} ),\quad \quad (2) $$\end{document}using ab initio molecular orbital methods. For the simpler system (1) a number of basis sets up to 6‐31G** and estimates of correlation energy by Moller‐Plesset perturbation theory up to the second ( MP 2) and the fourth ( MP 4) order were used for the catalyzed and uncatalyzed reactions, respectively. For the more complex system (2) Hartree‐Fock calculations using 3‐21G and 6‐31G basis sets were made. For these systems two reaction mechanisms have been examined: a two‐step and a concerted mechanism. The stationary points of each reaction, including intermediates and transition states, have been identified and free energies calculated for all geometry‐optimized reaction species to determine the thermodynamics and kinetics of the reaction. For both systems the calculations demonstrate that a second ammonia molecule catalyzes amide bond formation, and that the two‐step mechanism is more favorable than the concerted one for the catalyzed reaction, while for the uncatalyzed reaction both mechanisms are competitive. Correlation and polarization effects were found to be significant factors in stabilization and destabilization, respectively, of all transition states. Further, due to the cancellation of these two effects, the Hartee‐Fock calculations using 3‐21G and 6‐31G basis sets were found to be qualitatively identical to the results from the highest level calculations performed here.