The Interaction of Protonated Diglycine with Ammonia: A Density Functional Theory Model Study

The interaction of protonated diglycine, GLY 2 H +, with ammonia has been studied through density functional theory (DFT) calculations of structures and energetics at the B3LYP/6-31+G**// B3LYP/6-31+G** level. Five GLY 2 H + /NH 3 complexes were located which can be categorized as hydrogen-bonded ion/dipole complexes: one at the N-terminus, two at the C-terminus, and two at the amide bond. Two GLY 2 /NH 4 + complexes were located in which the proton had shifted from diglycine to ammonia: one at the N-terminus and one at the amide bond. Potential energy profiles including transition states were constructed. The profiles for complexation at the N-terminus and at the C-terminus demonstrate fairly deep wells (21 and 18 kcal/mol, respectively). The profile for complexation at the amide bond has a relatively shallow well (14 kcal/mol). The profiles for complexation at the N-terminus and at the amide bond are quite flat with very low intermediate barriers between the complexes. The computational results are discussed in the light of previously proposed mechanisms for H/D exchange between ND 3 and protonated peptides, in particular protonated diglycine. Exchange takes place at the N-terminus via the “onium” mechanism. The salt-bridge structure suggested as part of the H/D exchange mechanism at the C-terminus, in which the NH 4 + ion stabilizes a zwitterion structure of the peptide, is observed but only as a transition-state structure along the reaction profile. Exchange of the amide hydrogen takes place via a tautomerized peptide structure with a partial salt-bridge character. The relatively deep wells (∼20 kcal/mol) on the one hand and the shallow well (∼14 kcal/mol) on the other are in agreement with the previous observation of at least two chemically activated collision complexes with quite different lifetimes.