Investigation On The Fragmentation Behaviors Of Sulfonamides In Electrospray Tandem Mass Spectrometry

In electrospray ionization tandem mass spectrometry (ESI-MSn), dissociation of protonated molecules generates substantial fragment ions which contain structural information of molecules. Structure of molecules can be elucidated through analyzing the mass-charge (m/z), the relative abundance and the potential formation mechanism of product ions in the ESI-MS". However, the MS-based structural elucidation is often obscured and challenged because of the widespread rearrangement reactions in fragmentation of protonated molecules, such as methyl transfer, benzyl cation transfer and so on. It makes sense to explore these rearrangement reactions, which have also attracted the wide attention of mass spectrometrists. Sulfonamides have entensive bioactivity, and some of them have been developed as medicine and pesticide. However, there is still lack of systematic investigation on fragmentation reactions of sulfonamides. In this dissertation, several typical sulfonamides were selected as models to investigate the gas-phase dissociation reactions in ESI-MS, including the following four parts:1. Investigation on the tosyl oxygen transfer reaction:N-phenyl p-toluenesulfonamides were used as model compounds to investigate its MS fragmentation reations, including the tosyl oxygen atom transfer. Upon collisional activation, the protonated molecule underwent fragmentation reaction to give an ion/neutral complex [tosyl cation/aniline] (INC-1) via cleavage of the S-N bond. INC-1 underwent direct decomposition to generate tosyl cation, or electron transfer between the two partners of INC-1 occurred to yield aniline radical cation. What’ more, the O-C coupling reactions between the two partners of INC-1 took place to afford an ionic species of toluenesulfinates, which underwent the sequent cleavage of the S-O bond to give protonated quino-imines and another ion/neutral complex of [toluenesulfinyl cation/hydroxyaniline] (INC-2). And the subsequent electron transfer between the two partners of INC-2 resulted in hydroxyaniline radical cation. The protonated 34S isotopologue, the deuterium labeling experiments and theoretical calculations. Moreover, the presence of electron-donating groups on the para site of anilinic ring favorited the reaction channel of the tosyl transfer migration, whereas that of the electron-withdrawing groups inhibited this pathway.4. Investigation on the N-to the C-sulfonyl cation transfer:N-(3-phenyl-2H-chromen-2-ylidene)-benzenesulfonamides were used as model compounds to study the cyclization reaction via sulfonyl cation transfer in the MS/MS analysis. The ptotonated molecules underwent fragmentation via two main competing channels:a) dissociation of protonated molecules via breakage of the S-N bond gave an ion/neutral complex of [sulfonyl cation/imine] (INC), which underwent direct decomposition to generate the sulfonyl cation or electron transfer between the two partners of INC to give imine radical cation, b) The transferring sulfonyl cation was proposed to undergo the electrophilic attack at the ortho-site of the adjacent benzene ring, which resulted in activation of the ipso-hydrogen atom on the ring, and the activated hydrogen was subsequently transferred to the sulfonyl O atom via the adjacent imine group, which triggerred a cyclization reaction along with the loss of benzenesulfinic acid. The above migration of sulfonyl cation has been supported by the D-labeling experiment and theoretical calculations. Moreover, the presence of electron-donating groups on the benzene ring was found to favor the reaction channel of the sulfonyl cation migration, whereas that of electron-withdrawing groups inhibited this pathway.