Toward Closing the Gap between Hexoses and N‑Acetlyhexosamines: Experimental and Computational Studies on the Collision-Induced Dissociation of Hexosamines

Motivated by the fundamental difference in the reactivity of hexoses and N-acetylhexosamines under collision-induced dissociation (CID) mass spectrometry conditions, we have investigated the CID of two hexosamines, glucosamine (GlcN) and galactosamine (GalN), experimentally and computationally. Both hexosamines undergo ring-opening and then dissociate via the 0,2A and the 0,3A (0,3X) cross-ring cleavage channels. The preference for the ring-opening is similar to the behavior of N-acetylhexosamines and explains why the two anomers of the same sugar give the same mass spectrum. While the spectrum for GlcN is dominated by the 0,2A signal, the signal intensities for both 0,2A and the 0,3A (0,3X) dissociation channels are comparable for GalN, which allows GlcN and GalN to be distinguished easily. Calculations at MP2 level of theory indicate that this is related to the differences in the relative barrier heights for the 0,2A and the 0,3A (0,3X) cross-ring cleavage channels. This, in return, reflects the circumstance that the 0,2A cross-ring cleavage barriers are different for the two sugars, while the barriers of all other dissociation channels are comparable. While the mechanisms of the cross-ring dissociation channels of hexoses are well described using the retro–aldol mechanism in the literature, this study proposes a new mechanism for the 0,3A (0,3X) cross-ring cleavage of hexosamines that involves the formation of an epoxy intermediate or a zwitterionic intermediate.受己糖（hexoses）与N-乙酰己糖胺（N-acetylhexosamines）在碰撞诱导解离（collision-induced dissociation, CID）质谱条件下反应活性存在本质差异这一现象启发，我们通过实验与计算手段，对两种己糖胺——氨基葡萄糖（glucosamine, GlcN）与半乳糖胺（galactosamine, GalN）的CID行为展开了研究。两种己糖胺均会先发生开环反应，随后通过0,2A与0,3A（0,3X）跨环裂解通道发生解离。其开环反应的倾向性与N-乙酰己糖胺的行为相似，这也解释了为何同一糖的两种异头物会产生相同的质谱图。氨基葡萄糖的质谱以0,2A信号为主导，而半乳糖胺的0,2A与0,3A（0,3X）解离通道信号强度相当，这使得氨基葡萄糖与半乳糖胺能够被轻易区分。MP2理论级别下的计算结果表明，该现象与0,2A和0,3A（0,3X）跨环裂解通道的相对能垒高度差异相关。而这进一步反映出：两种己糖胺的0,2A跨环裂解能垒存在差异，而其余所有解离通道的能垒则较为相近。尽管现有文献中已利用逆羟醛缩合机制对己糖的跨环解离通道机制进行了充分阐释，但本研究针对己糖胺的0,3A（0,3X）跨环裂解提出了一种新机制，该机制涉及环氧中间体或两性离子中间体的形成。