A Hartree–Fock, MP2 and DFT computational study of the structures and energies of ″b2 ions derived from deprotonated peptides. A comparison of method and basis set used on relative product stabilities

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The doubly-protonated peptides Ala-Ala-Xaa-Ala-Ala-Ala-Arg show extensive loss of H 2 O when Xaa=Ser or Thr. Using quasi-MS 3 techniques the fragmentation reactions of the [M+2H -H 2 O] +2 ions have been studied in detail. For both Ser and Thr, the [M+2H -H 2 O] +2 ions show three primary fragmentation reactions, elimination of CH 3 CH=NH, elimination of one Ala residue, and elimination of two Ala residues, in all cases forming doubly-charged products. From a study of the further fragmentation of these products, it is concluded that elimination of two Ala residues results in formation of a three-membered aziridine ring by interaction with the adjacent amide function as H 2 O is lost. The elimination of one Ala residue results in formation of a five-membered oxazoline ring through interaction with the N-terminal adjacent carbonyl function as H 2 O is lost. The elimination of CH 3 CH=NH appears to involve formation of an eight-membered ring by interaction with the remote N-terminal carbonyl function as H 2 O is lost. However, this initial structure undergoes rearrangement through interaction with the adjacent C-terminal carbonyl function prior to further fragmentation. The [MH -H 2 O] + ion of Ala-Ala-Ser-Ala-Ala-Ala also shows elimination of CH 3 CH=NH, one Ala residue and two Ala residues.

Section: Resultsmentioning

confidence: 97%

Pathways for Water Loss from Doubly Protonated Peptides Containing Serine or Threonine

Harrison

2011

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“…Within this complex, proton abstraction may occur either from the nitrogen or the carbon to form the isomeric deprotonated diketopiperazines a and b. Our ab initio calculations [23] indicate that the C-deprotonated diketopiperazine b is ca. 10 kcal mol Ϫ1 higher in energy than the N-deprotonated species a, but that both the N™H and C™H bonds in the diketopiperazine are considerably more acidic than the C™H bond in benzene making proton abstraction from either position exothermic.…”

Section: D]mentioning

confidence: 82%

“…An alternative pathway to m/z 113, outlined in Scheme 6, involves proton abstraction from the N-terminal amide position leading to the phenyl anion/neutral complex shown. Ab initio calculations [23] show that the isocyanato neutral in the complex is only 6 -7 kcal mol Ϫ1 higher in energy than the diketopiperazine of Scheme 5 and that the anion d derived by N™H deprotonation has essentially the same energy as the N-deprotonated diketopiperazine a. The anion c is 17.5 kcal mol Ϫ1 higher in energy than a or d but proton abstraction from this position by the phenyl anion remains exothermic [23].…”

Section: D]mentioning

confidence: 99%

“…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. 23 kcal mol Ϫ1 exothermic.…”

mentioning

confidence: 99%

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Fragmentation of deprotonated N-benzoylpeptides: Formation of deprotonated oxazolones

Harrison

Young

2004

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The fragmentation reactions of deprotonated N-benzoyl peptides, specifically hippurylglycine, hippurylglyclyclycine, and hippurylphenylalanine (hippuryl ϭ N-benzoylGly) have been studied using MS 2 and MS 3 experiments as well as deuterium labeling. A major fragment ion is observed at m/z 160 ([C 9 H 6 NO 2 ] Ϫ ) which, upon collisional activation, mainly eliminates CO 2 indicating that the two oxygen atoms have become bonded to the same carbon. This observation is rationalized in terms of formation of deprotonated 2-phenyl-5-oxazolone. Various pathways to the deprotonated oxazolone have been elucidated through MS 3 experiments. Fragmentation of deprotonated N-acetylalanylalanine gives a relatively weak signal at m/z 112 which, upon collisional activation, fragments, in part, by loss of CO 2 leading to the conclusion that the m/z 112 ion is deprotonated 2,4-dimethyl-5-oxazolone. -4]. When the charge resides on the C-terminal fragment a protonated amino acid (y 1 Љ) or smaller protonated peptide (y n Љ) ion is formed [5,6]. When the charge resides on the Nterminal fragment the b ions formed, rather than having the expected acylium ion structure, have, in many cases, cyclized to form a protonated oxazolone [7][8][9][10][11][12]. Recent work by O'Hair and co-workers [13] suggests that in some cases alternative cyclic structures may be more stable than the oxazolone structure and thus, may be preferentially formed. Formation of oxazolone structures also rationalizes the observation that, while b 1 ions rarely are formed by cleavage of the first amide bond, N-acylation of the peptide frequently leads to cleavage of the N-terminal peptide amide bond since stable oxazolones can be formed [7,9,14].Nominal amide bond cleavage also occurs for deprotonated peptides, as illustrated in Scheme 1, where the y n ions are deprotonated amino acids (y 1 ) or peptides (y n ) and the Љb n ions bear two fewer hydrogens than the corresponding b n ions formed from protonated peptides. Formation of Љb n ions was first noted by Heerma and co-workers [15,16] and elaborated upon by Bowie and co-workers [17][18][19]. The latter authors proposed the mechanism outlined in Scheme 2 for formation of Љb 2 ions, designating the pathway leading to the deprotonated amino acid as ␣-cleavage and that leading to the charged N-terminal fragment as ␤-cleavage. From a low-energy CID study of deprotonated tripeptides, Harrison [20] proposed a similar direct cleavage of the amide bond but suggested that the charged N-terminal fragment had cyclized to form a deprotonated oxazolone. 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 fragment...

“…Next, we considered the formation processes of [b 2 -H + Zn] + by peptide bond cleavage of the even-electron complex 1Zn + containing a deprotonated amide group (Scheme 6). In the case of CID of the deprotonated peptide, the negative charge on the amide group is reported to induce peptide bond cleavage, forming oxazolone b and deprotonated y' fragments [38]. Although the intermediate 1Zn + is a singly charged positive ion, the negative charge on amide nitrogen would induce peptide bond cleavage, producing oxazolone b and deprotonated y' fragments.…”

Section: Ecd Fragmentation Mechanism Of Zn 2+ -Trihistidine Complexesmentioning

confidence: 99%

Difference of Electron Capture and Transfer Dissociation Mass Spectrometry on Ni²⁺-, Cu²⁺-, and Zn²⁺-Polyhistidine Complexes in the Absence of Remote Protons

Asakawa

Pauw

2016

Abstract. Electron capture dissociation (ECD) and electron transfer dissociation (ETD) in metal-peptide complexes are dependent on the metal cation in the complex. The divalent transition metals Ni 2+ , Cu 2+ , and Zn 2+ were used as charge carriers to produce metal-polyhistidine complexes in the absence of remote protons, since these metal cations strongly bind to neutral histidine residues in peptides. In the case of the ECD and ETD of Cu 2+ -polyhistidine complexes, the metal cation in the complex was reduced and the recombination energy was redistributed throughout the peptide to lead a zwitterionic peptide form having a protonated histidine residue and a deprotonated amide nitrogen. The zwitterion then underwent peptide bond cleavage, producing a and b fragment ions. In contrast, ECD and ETD induced different fragmentation processes in Zn 2+ -polyhistidine complexes. Although the N-C α bond in the Zn 2+ -polyhistidine complex was cleaved by ETD, ECD of Zn 2+ -polyhistidine induced peptide bond cleavage accompanied with hydrogen atom release. The different fragmentation modes by ECD and ETD originated from the different electronic states of the charge-reduced complexes resulting from these processes. The details of the fragmentation processes were investigated by density functional theory.