Computational estimates of the gas-phase basicity and proton affinity of glutamic acid

Literature values for the gas-phase basicity (GB) and proton affinity (PA) of glutamic acid range from 216 to 224 kcal/mol (GB) and 218 to 241 kcal/mo l (PA). In this paper, a high-level theoretical study aimed at resolving th e apparent disagreement among the experimental values is presented. Hartree -Fock, MP2, and DFT calculations with lar ge basis sets were carried out on the neutral and protonated forms of glutamic acid. Nine protonated and 21 neutral conformers were located at the HF/3-21G and B3LYP/6-31+G** levels w ith full geometry optimization and characterization of stationary points. T he energetics were subsequently reevaluated at the MP2(full)/6-311 + G(2d,p )//B3LYP/6-31 + G** level. Thermodynamic data in the harmonic approximation were obtained at the B3LYP/6-31+G**: level. This data was used to estimate the gas-phase distribution of conformers at 298 K, The lowest energy struc tures of protonated and neutral glutamic acid both exhibit cyclic structure s due to the formation of intramolecular hydrogen bonds. The calculated PA and GB are 224.4 and 214.4 kcal/mol, respectively. It is shown that, when c ertain empirical corrections for the entropy of cyclization are omitted and appropriate adjustments are made to thermodynamic scales, the GB and gas-p hase PA values reported here are in excellent agreement with a variety of p revious experimental measurements.