The quantum chemical mass spectrometry for materials science (QCMS) method is used to verify the proposed mechanism for proton transfer - the Mobile Proton Model (MPM) - by histidine for ten XHS tripeptides, based on quantum chemical calculations at the DFT/B3LYP/6-311+G* level of theory. The fragmentations of the different intermediate structures in the MPM mechanism are studied within the QCMS framework, and the energetics of the proposed mechanism itself and those of the fragmentations of the intermediate structures are compared, leading to the computational confirmation of the MPM. In addition, the calculations suggest that the mechanism should be extended from considering only the formation of five-membered ring intermediates to include larger-ring intermediates. Graphical Abstract ᅟ.
The identification of peptides and proteins from tandem mass spectra is a difficult task and multiple tools have been developed to aid this identification. We present a new method, called Quantum Chemical Mass Spectrometry for Materials Science (QCMS 2 ), which is based on quantum chemical calculations of bond orders, reaction and transition-state energies at the DFT/B3LYP/6-311+G* level of theory. The method was used to describe the fragmentation pathways of five X-His-Ser tripeptides with X = Asn, Asp, Glu, Ser and Trp, thereby focusing on the influence of the side chain and inter-side-chain interaction on the fragmentation. The main features in the mass spectra of the five tripeptides were correctly reproduced and a number of fragments were assigned to fragmentations involving the side chain and the influence of inter-side-chain interactions. Product ion spectra were recorded to evaluate the capabilities and limitations of QCMS 2 and a number of conventional tools.
Rationale: Both amide bond protonation triggering peptide fragmentations and the controversial b 2 -ion structures have been subjects of intense research. The involvement of histidine (H), with its imidazole side chain that induces specific dissociation patterns involving inter-side-chain (ISC) interactions, in b 2 -ion formation was investigated, focusing on the QHS model tripeptide.
Methods:To identify the effect of histidine on fragmentations issued from ISC interactions, QHS was selected for a comprehensive analysis of the pathways leading to the three possible b 2 -ion structures, using quantum chemical calculations performed at the DFT/B3LYP/6-311+G* level of theory. Electrospray ionization ion trap mass spectrometry allowed the recording of MS 2 and MS 3 tandem mass spectra, whereas the Quantum Chemical Mass Spectrometry for Materials Science (QCMS 2 ) method was used to predict fragmentation patterns.
Results:Whereas it is very difficult to differentiate among protonated oxazolone, diketopiperazine, or lactam b 2 -ions using MS 2 and MS 3 mass spectra, the calculations indicated that the QH b 2 -ion (detected at m/z 266) is probably a mixture of the lactam and oxazolone structures formed after amide nitrogen protonation, making the formation of diketopiperazine less likely as it requires an additional step for its formation.
Conclusions:In contrast to glycine-histidine-containing b 2 -ions, known to be issued from the backbone-imidazole cyclization, we found that interactions between the side chains were not obvious to perceive, neither from a thermodynamics nor from a fragmentation perspective, emphasizing the importance of the whole sequence on the dissociation behavior usually demonstrated from simple glycine-containing tripeptides.
The conformational and configurational preferences of Me2P-N=S=N-PMe2 (3) and Me2P-N=S=N-AsMe2 (4) have been identified using quantum chemical calculations at the DFT/B3LYP/6-311+G* level of theory. An approach in which energetic, structural (geometries and bond orders), electronic (analysis of the electron density) and spectroscopic properties are combined leads to the conclusion that these sulfur-nitrogen-pnictogen chains share many of the properties of their chalcogen-nitrogen analogues but that the through-space intramolecular interactions favouring the Z,Z configuration are even weaker than in these latter compounds. The results of this analysis also lead to an unambiguous assignment of the variable-temperature 31 P and 15 N NMR spectra of these compounds and their structures both in solution and in the solid state.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.