Collision-induced dissociation of Na+-tagged ketohexoses: experimental and computational studies on fructose

Collision-induced dissociation tandem mass spectrometry (CID-MSn) and computational investigation at the MP2/6-311+G(d,p) level of theory have been employed to study Na+-tagged fructose, an example of a ketohexose featuring four cyclic isomers: alpha-fructofuranose (alpha Fruf), beta-fructofuranose (beta Fruf), alpha-fructopyranose (alpha Frup), and beta-fructopyranose (beta Frup). The four isomers can be separated by high-performance liquid chromatography (HPLC) and they show different mass spectra, indicating that CID-MSn can distinguish the different fructose forms. Based on a simulation using a micro-kinetic model, we have obtained an overview of the mechanisms for the different dissociation pathways. It has been demonstrated that the preference for the C-C cleavage over the competing isomerization of linear fructose is the main reason for the previously reported differences between the CID-MS spectra of aldohexoses and ketohexoses. In addition, the kinetic modeling helped to confirm the assignment of the different measured mass spectra to the different fructose isomers. The previously reported assignment based on the peak intensities in the HPLC chromatogram had left some open questions as the preference for the dehydration channels did not always follow trends previously observed for aldohexoses. Setting up the kinetic model further enabled us to directly compare the computational and experimental results, which indicated that the model can reproduce most trends in the differences between the dissociation pathways of the four cyclic fructose isomers.

Automated summary

Collision-induced dissociation tandem mass spectrometry (CID-MSn) and computational investigation were used to study the dissociation pathways of Na+-tagged fructose. Different cyclic isomers of fructose showed distinct mass spectra, indicating the ability of CID-MSn to distinguish them. Kinetic modeling helped explain previous discrepancies and confirmed the assignment of different mass spectra to fructose isomers. The model was able to reproduce most trends observed in the differences between the dissociation pathways of the cyclic fructose isomers.