Computational approach to the proton affinities of Glyn (n = 1–10)

The proton affinities of a series of polyglycines were calculated as a function of molecular size up to Gly 10 . Molecular mechanics calculations using the Merck molecular mechanics force field were used to find lowest energy structures. These structures were used as starting geometries for both semiempirical and density functional calculations. Local density approximation density functional theory (DFT) (Slater exchange/VWN correlation or S-VWN, 6-31G∗) was used to refine the geometries obtained from the mechanics. B3LYP (6-31G∗) energies were calculated using these S-VWN geometries. The results of these calculations are compared to previously measured experimental data. The average deviation between the B3LYP and S-VWN proton affinities and the experimentally measured values of Fenselau and co-workers [J. Am. Soc. Mass Spectrom. 3 (1992) 863] are 4.0 and 2.0 kcal/mol, respectively. Better agreement to the experimentally measured values is obtained if the proton affinities are normalized to that of glycine. As expected, the DFT values are in better agreement than the semiempirical (AM1 and PM3) values. For the semiempirical methods, the average deviation from the proton affinities measured by Fenselau and co-workers (all data normalized to glycine) is ∼4.5 kcal/mol. For proton affinities calculated with B3LYP hybrid functionals, this average deviation is only 1.2 kcal/mol (this deviation does not directly reflect the accuracy of the calculations since there are errors in both the experimental and calculated values). For pentaglycine, optimization was performed at the B3LYP 6-311G∗∗ level; the proton affinity differed by only 1 kcal/mol over that calculated at the 6-31G∗ level. This suggests that the lower basis set is sufficient for this application. The energies of the zwitterionic forms of Gly n ( n = 4, 5, 7, and 10) were compared to those of the simple protonated form. The zwitterion form of each polyglycine was found to be less stable at all levels of theory. These results suggest that it is possible to obtain accurate thermochemical data using mechanics and DFT calculations even for these relatively large molecules.