Experimental and ab initio studies of the gas-phase basicities of polyglycines

Article abstract of DOI:10.1021/ja00076a044

The gas-phase basicities of polyglycines, Gly_n (n = 1-6), were determined by proton transfer reactions in a Fourier transform ion cyclotron resonance mass spectrometer. The basicities were found to increase as the peptide chain length increased: 206.2, 215.3, 218.9, 225.0, 225.3, and 227.4 kcal/mol for n = 1-6, respectively. Comparable results, but with some deviations, were obtained using the kinetic method of collision-induced dissociation on a proton-bound dimer. The large change in basicity between glycine and diglycine suggests significant differences in the strength of intramolecular hydrogen bonding in their protonated forms. This is consistent with ab initio Hartree-Fock calculations, which were carried out using the 6-31G * basis set for glycine, diglycine, and their protonated species. Full optimization of geometry yielded eight minimum-energy structures: glycine (1), protonated glycines at the amino nitrogen (2) and the carbonyl oxygen (3), diglycine (4), and protonated diglycines at the amino nitrogen (5), the amide carbonyl oxygen (6), the amide nitrogen (7), and the carboxyl carbonyl oxygen (8). The ideal-gas basicities for the relevant protonations at 298.15 K and 1 atm, calculated after inclusion of zero-point energy and temperature changes in enthalpy and entropy, were found to be 207.5 (1 → 2), 194.3 (1 → 3), 214.0 (4 → 5), 212.9 (4 → 6), 196.9 (4 → 7), and 188.3 (4 → 8) kcal/mol. For the glycines, more accurate electronic energies were obtained with geometry optimization in the larger 6-31+G(d,p) basis, including electron correlation corrected to the fourth order in the M?ller-Plesset perturbation treatment. Scaling the zero-point energy with a factor of 0.91 was also found to improve the calculated basicities. The best theoretical estimates of basicities corresponding to protonation at the terminal amine were 206.3 and 215.2 kcal/ mol for the respective glycine and diglycine; these numerical values are in excellent agreement with the experimental gas-phase basicities. The corresponding theoretical and experimental proton affinities are also presented. Detailed analysis is made on the structural features that affect the relative stabilities of the various molecular species. In addition, several topics relevant to the theoretical and experimental determinations of basicity are discussed.