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 (0,2)A and the (0,3)A (X-0,X-3) 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 (0,2)A signal, the signal intensities for both (0,2)A and the (0,3)A (X-0,X-3) 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 (0,2)A and the (0,3)A (X-0,X-3) cross-ring cleavage channels. This, in return, reflects the circumstance that the (0,2)A 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 (0,3)A (X-0,X-3) cross-ring cleavage of hexosamines that involves the formation of an epoxy intermediate or a zwitterionic intermediate.