Prediction of electronically nonadiabatic decomposition mechanisms of isolated gas phase nitrogen-rich energetic salt: Guanidium-triazolate

Eur J Mass Spectrom (Chichester)

Liu

et al. 2019

Fragmentation mechanisms of the singly protonated glutathione ( γ-ECG) and its synthetic analogue peptides (ECG and PPECG) have been investigated by liquid chromatography tandem-mass spectrometry and theoretical calculations. In the mass spectra, similar fragmentation patterns were observed for γ-ECG and ECG, but a completely different one was found in the case of PPECG. The E–C amide bond cleavage is the predominant pathway for the fragmentation of γ-ECG and ECG, whereas the additional N-terminal prolyl residues in PPECG significantly suppress the E–C amide bond cleavage. Theoretical calculations reveal that the fragmentation efficiencies of the E–C bonds in the protonated γ-ECG and ECG are much higher than that in the protonated PPECG, being attributed to their lower barriers of the potential energy; clearly the introduction of two prolyl residues can increase substantially the potential energy barrier. In the proposed mechanism, the protonated E–C amide bonds in the three peptides are first weakened followed by a nucleophilic addition by the glutamyl carboxyl oxygen atom in side chain, leading to the breaking of the E–C amide bonds. However, the processes of E–C bond fragmentation for three protonated analogs were not collaborative. Protonated amide bonds first fragment, then the nucleophilic addition by the side chain of glutamyl carboxyl oxygen atom takes places. On the other hand, the prolyl residues in PPECG can largely diminish the nucleophilic addition, resulting in a much lower efficiency of its E–C amide bond breaking. Distance analysis indicates that breaking the E–C amide bonds in the protonated γ-ECG, ECG, and PPECG ions could not occur without the assistance from the nucleophilic attack, highlighting an asynchronous collaborative process in the bond breakings.

Section: Computational Detailsmentioning

confidence: 95%

Insight into nucleophilic fragmentation mechanisms by glutamic acid side chain in singly protonated glutathione and related peptidyl ions

Fan

Eur J Mass Spectrom (Chichester)

Liu

et al. 2019

“…The structure with the lowest energy was selected to perform a geometric optimization and to search reaction pathways at the B3LYP/def‐TZVP level using Turbomole supported by ChemShell 3.7.0 33 . Key transition states with only one imaginary frequency were further validated by intrinsic reaction coordinate calculations to confirm their connections 34–37 …”

Section: Experimental and Theoretical Methodsmentioning

confidence: 99%

Mass spectral and theoretical investigations of N–C^αbond cleavages in the disulfide‐containing peptide TTCPYCKK and its analogues

Rapid Comm Mass Spectrometry

Tian

et al. 2022

Rationale For disulfide‐containing peptides, mass spectrometric analyses are rarely comparably studied between their dithiol and disulfide forms. Persulfide ions afforded from peptides with a disulfide ring are from either an unusual N–Cα bond cleavage or a canonical peptide bond cleavage; their isomeric structures are, however, not identified just from peaks of mass spectra. Methods Isomeric structures of [C3P4X5|C6M], [C3MAP4X5|C6MB] and [P4X5C6|C3M] were identified from a series of the X5 substituted dicysteine octapeptides using electrospray ionization tandem mass spectrometry for both their dithiol and disulfide forms. Formation mechanisms of different persulfide ions were investigated systematically by theoretical methods. Moreover, electrostatic potential‐mapped molecular van der Waals surfaces were used to determine the stabilities of the intermediates, which gave a further evaluation of favored bond cleavage. Results Mass spectral analyses indicated that the fragmented ions changed largely when an intramolecular disulfide bond was formed. New types of disulfide‐containing fragmented ions [C3P4X5|C6M] or [C3MAP4X5|C6MB] were thus proposed. Energy analysis showed that the N–Cα cleavage was not competitive energetically with that of the amide bond for Y5 and its phosphorylated analogue. However, the N–Cα cleavage products dominated for the S5‐ and T5‐containing peptides. Stabilities of the intermediates were found to be related with the electrostatic potential‐mapped molecular van der Waals surfaces. Conclusions Persulfide ions containing more residues than previously found were proposed not only from b7 ions but also from y6 ions. In addition, a new kind of phosphorylated analogue, [C3P4pY5|C6M], is reported in this work. Our study provides convincing results for separating isomeric structures in the cases of N–Cα cleavages, which greatly assists in the structural identification of disulfide‐containing peptides.

“…34 Key transition states with only one imaginary frequency were further validated by intrinsic reaction coordinate (IRC) calculations to conrm their connections. [35][36][37] 2.2.2 Analysis by atoms-in-molecules (AIM). The AIM theory has been demonstrated to be a very useful approach to explore non-covalent bonding interactions employing electron density and laplacian at the critical points with the utilization of the optimized structures.…”

Section: Theoretical Methodsmentioning

confidence: 99%

Mass spectral and theoretical investigations of the transient proton-bound dimers on the cleavage processes of the peptide GHK and its analogues

Zhang

et al. 2021

RSC Adv.