RATIONALE Both amide bond protonation triggering peptide fragmentations and the controversial b2 -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 b2 -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 b2 -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 MS2 and MS3 tandem mass spectra, whereas the Quantum Chemical Mass Spectrometry for Materials Science (QCMS2 ) method was used to predict fragmentation patterns. RESULTS Whereas it is very difficult to differentiate among protonated oxazolone, diketopiperazine, or lactam b2 -ions using MS2 and MS3 mass spectra, the calculations indicated that the QH b2 -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 b2 -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.

中文翻译：

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量子化学质谱：从头算研究单质子化的Gln-His-Ser三肽的b2离子形成机理。

理由：酰胺键质子化触发肽片段化和有争议的b2离子结构都已经得到了广泛的研究。研究了组氨酸（H）及其咪唑侧链可诱导涉及侧链间（ISC）相互作用的特定解离模式，参与了b2-离子的形成，重点研究了QHS模型三肽。方法为了鉴定组氨酸对ISC相互作用产生的片段化的影响，选择QHS进行了DFT / B3LYP / 6-311 + G量子化学计算，全面分析了导致三种可能的b2-离子结构的途径。 *理论水平。电喷雾电离离子阱质谱法可以记录MS2和MS3串联质谱，而使用材料科学的量子化学质谱（QCMS2）方法来预测碎裂模式。结果尽管使用MS2和MS3质谱很难区分质子化的恶唑酮，二酮哌嗪或内酰胺b2-离子，但计算表明QH b2离子（在m / z 266处检测到）可能是内酰胺的混合物酰胺氮质子化后形成的恶唑酮结构和恶唑酮结构，使二酮哌嗪的形成可能性降低，因为它需要额外的形成步骤。结论与已知由主链-咪唑环化反应产生的含甘氨酸-组氨酸的b2-离子相反，我们发现，无论从热力学还是从断裂角度来看，侧链之间的相互作用都不明显。