Proton migration and tautomerism in protonated triglycine

Proton migration in protonated glycylglycylglycine (GGG) has been investiga ted by using density functional theory at the B3LYP/6-31++G(d,p) level of t heory. On the protonated GGG energy hypersurface 19 critical points have be en characterized, 11 as minima and 8 as first-order saddle points. Transiti on state structures for interconversion between eight of these minima are r eported, starting from a structure in which there is protonation at the ami no nitrogen of the N-terminal glycyl residue following the migration of the proton until there is fragmentation into protonated 2-aminomethyl-5-oxazol one (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 protonati on 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 ni trogen atom, resulting in a compact five-membered ring. Another oxygen-prot onated 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. Proton ation on the N-terminal nitrogen atom produces an isomer that is about 1 kc al mol(-1) higher in for energy than isomers resulting from protonation on the carbonyl oxygen of the N-terminal residue. The calculated energy barrie r to generate the bz 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 m ol(-1) lower than those from previous calculations and are in excellent agr eement with recently revised experimental values.