Arginine-facilitated isomerization: Radical-induced dissociation of aliphatic radical cationic glycylarginyl(iso)leucine tripeptides

Abstract

The gas phase fragmentations of aliphatic radical cationic glycylglycyl(iso)leucine tripeptides ([G•G(L/I)] +), with well-defined initial locations of the radical centers at their N-terminal α-carbon atoms, are significantly different from those of their basic glycylarginyl(iso)leucine ([G•R(L/I)] +) counterparts; the former lead predominantly to [b 2 - H] •+ fragment ions, whereas the latter result in the formation of characteristic product ions via the losses of •CH(CH 3) 2 from [G•RL] + and •CH 2CH 3 from [G•RI] + through C β-C γ side-chain cleavages of the (iso)leucine residues, making these two peptides distinguishable. The α-carbon-centered radical at the leucine residue is the key intermediate that triggers the subsequent C β-C γ bond cleavage, as supported by the absence of •CH(CH 3) 2 loss from the collision-induced dissociation of [G•RL α-Me] +, a radical cation for which the α-hydrogen atom of the leucine residue had been substituted by a methyl group. Density functional theory calculations at the B3LYP 6-31++G(d,p) level of theory supported the notion that the highly basic arginine residue could not only increase the energy barriers against charge-induced dissociation pathways but also decrease the energy barriers against hydrogen atom transfers in the GR(L/I) radical cations by ∼10 kcal mol -1, thereby allowing the intermediate precursors containing α- and γ-carbon-centered radicals at the (iso)leucine residues to be formed more readily prior to promoting subsequent C β-C γ and C α-C β bond cleavages. The hydrogen atom transfer barriers for the α- and γ-carbon-centered GR(L/I) radical cations (roughly in the range 29-34 kcal mol -1) are comparable with those of the competitive side-chain cleavage processes. The transition structures for the elimination of •CH(CH 3) 2 and •CH 2CH 3 from the (iso)leucine side chains possess similar structures, but slightly different dissociation barriers of 31.9 and 34.0 kcal mol -1, respectively; the energy barriers for the elimination of the alkenes CH 2=CH(CH 3) 2 and CH 3CH=CHCH 3 through C α-C β bond cleavages of γ-carbon-centered radicals at the (iso)leucine side chains are 29.1 and 32.8 kcal mol -1, respectively. © 2012 American Chemical Society.