Fragmentation Reactions of a₂ Ions Derived From Deprotonated DipeptidesA Synergy Between Experiment and Theory

Abstract

The fragmentation reactions of a number of a2 ions ([M−H−CO2]-) derived from dipeptides have been studied by energy-resolved mass spectrometry, isotopic labeling, and MS3 experiments. The general reaction sequence leading eventually to a deprotonated amine, is shown to occur, a reaction sequence first proposed by Styles and O'Hair (Rapid Commun. Mass Spectrom. 1998, 12, 809) from a study of the a2 ion derived from glycylglycine. When an amidic hydrogen (R2 = H) is present, the initial proton-transfer reaction 1 is nonreversible. However, when there is no amidic hydrogen, as in the a2 ions derived from H−Ala−Pro−OH or H−Gly−Sar−OH, the initial proton-transfer reaction 1 becomes reversible, leading to the interchange of N-bonded and C-bonded hydrogens. Ab initio calculations at the MP2/6-31+G(d) level of the energies and interconversion pathways of anions derived by deprotonation of glycine N-methylamide show a barrier of 8 kcal mol-1 for reaction 1, with reaction 2 being 23.8 kcal mol-1 endothermic. When an amidic hydrogen (R2 = H) is present, the amine-deprotonated species formed in reaction 1 abstracts a proton from the amide nitrogen to form the amide-deprotonated species, the most stable species on the potential energy surface. The system effectively becomes trapped in this low-energy well and exits upon activation by reactions 2 and 3 as observed when glycine N-methylamide is deprotonated directly. When no amidic hydrogen is present, this low-energy state does not exist, and reaction 1 becomes reversible, leading to the interchange of N-bonded and C-bonded hydrogens. In these cases, a significant population of the original a2 ion is formed, which fragments by the reaction

Fragmentation reactions of deprotonated peptides containing proline. The proline effect

“…32 In agreement with the results of Bowie and coworkers, 24 the major primary fragmentation reactions involve elimination of CO 2 to form the a 2 ion and formation of the y 1 ion (Scheme 1). In the present work, we have studied the tandem mass spectra of deprotonated H-Pro-Ala-OH and H-Pro-Val-OH using the Q-ToF instrument.…”

“…Bowie and coworkers 24 reported unexpected ion signals at m/z 113 and m/z 72 in the high-energy CID of the former while there is an unexpected ion signal at m/z 141 for the latter. 32 Table 3 records the CID mass spectra for deprotonated HPro-Gly-Gly-OH and two fragment ions derived therefrom as obtained on the Q-ToF instrument at 20 eV collision energy. Five product ions are observed on fragmentation of the in high-energy CID studies, reported observation of the a 3 , 00 b 2 and y 1 ion, although the signal for the last product was quite weak.…”

Fragmentation of deprotonated N-benzoylpeptides: Formation of deprotonated oxazolones

“…More recent studies [21] have shown that a major pathway to Љb 2 ions from deprotonated tripeptides involves loss of a neutral amine from the a 3 ([M Ϫ H Ϫ CO 2 ] Ϫ ) ion, as illustrated in Scheme 3, where again it is proposed that the Љb 2 ion is a deprotonated oxazolone. The initial proton transfer reaction in Scheme 3 (and in later schemes) is undoubtedly exothermic but most likely involves a rotational barrier similar to the rotational barriers observed [22] in the fragmentation of a 2 ions derived from deprotonated dipeptides. Recent ab initio calculations in this laboratory [23] show that the Љb 2 ion structure proposed in Scheme 2 readily rearranges over low energy rotational barriers to form the deprotonated oxazolone of Scheme 3, a cyclization which is ca.…”

Characterization of the Conformational Probability of N-Acetyl-Phenylalanyl-NH2by RHF, DFT, and MP2 Computation and AIM Analyses, Confirmed by Jet-Cooled Infrared Data

“…3,[40][41] The systematic construction of the Ac-Phe-NH 2 peptide model using precomputed molecular moiety 'modules' also benefited from the use of precomputed data. In turn, the constituent and 'total' Ac-Phe-NH 2 module will itself be able to be used in subsequent studies of larger and more complex (di-, tri-, oligo-) peptide systems containing Phe.…”

“…The large number of conformers is necessary to accurately characterize the topologically probable (stable) set of conformers emerging from the topologically possible set. [1][2][3][4]17,18,40,42,[50][51][52][53][54] Conformational nomenclature follows the rules outlined in the literature. [1][2][3][4]17,18,40,[50][51][52][53][54] The i 2 side chain dihedral angle (phenyl ring rotor) was modeled in the gauche + (g + ), anti (a), and gauche -(g -) conformations.…”