Proton migration and tautomerism in protonated triglycine

Proton migration in protonated glycylglycylglycine (GGG) has been investigated by using density functional theory at the B3LYP/6-31++G(d,p) level of theory. On the protonated GGG energy hypersurface 19 critical points have been characterized, 11 as minima and 8 as first-order saddle points. Transition state structures for interconversion between eight of these minima are reported, starting from a structure in which there is protonation at the amino nitrogen of the N-terminal glycyl residue following the migration of the proton until there is fragmentation into protonated 2-aminomethyl-5-oxazolone (the b 2 ion) and glycine. Individual free energy barriers are small, ranging from 4.3 to 18.1 kcal mol -1. The most favorable site of protonation on GGG is the carbonyl oxygen of the N-terminal residue. This isomer is stabilized by a hydrogen bond of the type O-H···N with the N-terminal nitrogen atom, resulting in a compact five-membered ring. Another oxygen-protonated isomer with hydrogen bonding of the type O-H···O, resulting in a seven-membered ring, is only 0.1 kcal mol -1 higher in free energy. Protonation on the N-terminal nitrogen atom produces an isomer that is about 1 kcal mol -1 higher in free energy than isomers resulting from protonation on the carbonyl oxygen of the N-terminal residue. The calculated energy barrier to generate the b 2 ion from protonated GGG is 32.5 kcal mol -1 via TS(6→7). The calculated basicity and proton affinity of GGG from our results are 216.3 and 223.8 kcal mol -1, respectively, These values are 3-4 kcal mol -1 lower than those from previous calculations and are in excellent agreement with recently revised experimental values.link_to_subscribed_fulltex

Solvent-assisted rearrangements between tautomers of protonated peptides

The presence of an interacting water or methanol molecule has been shown to catalyze the 1,3-proton shift in a peptide linkage between the tautomers of protonated formamide and glycylglycylglycine. Density functional theory calculations at the B3LYP/6-31++G(d,p) level of theory show that, for glycylglycylglycine, the forward barrier of this shift decreases from a free energy at 298 K of 39.6 kcal/mol in the absence of solvent to 26.7 kcal/mol in the presence of water and to 22.0 kcal/mol in the presence of methanol. Protonation at the amide nitrogen of the second residue results in a large increase in the C-N bond distance from 1.336 to 1.519 Å, whereas protonation at the carbonyl oxygen leads to a decrease in the C-N bond distance from 1.336 to 1.321 Å. Solvent-catalyzed tautomerism may play an important role in the fragmentation of electrosprayed, protonated peptides in the gas phase. © 2000 American Chemical Society.link_to_subscribed_fulltex