Decarboxylation mechanism of amino acids by density functional theory

The decarboxylation mechanisms of amino acids with and without water were studied by density functional theory at the 133LYP/6-31G level. Without water, two decarboxylation channels exist for the low molecular weight amino acids glycine (Gly) and alanine (Ala), whereas only one exists for the other amino acids. Channel one for Gly and Ala takes place from a neutral conformer in which the carboxylic hydrogen is intramolecularly hydrogen bonded to the nitrogen atom of the amino group. During the development of the transition-state structure, the carboxylic hydrogen atom first shifts to the amino group forming the zwitterion and then from the -NH3+ group to the a-carbon forming the product amine. Accompanying proton transfer, the C-CO2 bond elongates. Channel two starts from the higher-energy anti carboxylic hydrogen conformer and involves the direct heterolytic loss of CO2 accompanied by simultaneous proton transfer. The calculated energy barriers range from 288 to 307 kJ/mol with an average of 299 kJ/mol. The decarboxylation channels and side-chain structures have a negligible effect on the energy barriers. The water-catalyzed transition-state structures start from the zwitterion in which a water molecule is hydrogen bonded between the carboxylate group and -NH3+ Group and have imaginary frequencies that correspond to "swinging" of the water molecule from the carboxylate oxygen to the a-carbon. The calculated energy barriers range from 177 to 195 kJ/mol with an average of 186 kJ/mol. An intrinsic reaction coordinate analysis indicates that crossing the energy barrier does not take the activated complex forward in the direction of the products. However, geometry optimization of the carbanion-water activated complex after the loss of CO2 leads to the formation of the product amine and the water molecule. Consequently, solvent dynamics and steric effects in the solvated transition state are responsible for the difference in the relative decarboxylation rates of amino acids. The transition-state structures are less polar than the reactants, which confirms experimental findings about the salt effect.