Fragmentation reactions of thiourea- and urea-compounds examined by tandem MS-, energy-resolved CID experiments, and theory

Predicting collision-induced dissociation mass spectra: understanding the role of the mobile proton in small molecule fragmentation

“…As discussed in the Introduction, the mobile proton model is commonly applied to the fragmentation of protonated peptides [1][2][3] and it is increasingly used to explain the fragmentation of lower molecular weight molecules (defined here as 1000 Da or less). [12][13][14][15][16][17][18][19] The qualitative observations (and energy calculations) made on the product ions formed at collision energies in the range 5 to 50 eV from the seven compounds investigated in this study suggest that there is no significant energy barrier to proton migration. The proton appears to be able to migrate around these molecules, causing charge-directed fragmentation when it reaches a 'dissociative site'.…”

“…This work has contributed to the understanding of the role of the mobile proton in fragmentation of small molecules. As discussed in the Introduction, the mobile proton model is commonly applied to the fragmentation of protonated peptides and it is increasingly used to explain the fragmentation of lower molecular weight molecules (defined here as 1000 Da or less) . The qualitative observations (and energy calculations) made on the product ions formed at collision energies in the range 5 to 50 eV from the seven compounds investigated in this study suggest that there is no significant energy barrier to proton migration.…”

“…There are examples of proton migration for many classes of compounds: The product ion spectrum of protonated penicillin contains ions resulting from cleavage of the β‐lactam bond after transfer of the proton from the carbonyl to the lactam nitrogen, [ 14 ] while dibenzyl ether, [ 15 ] the pharmaceutical compounds maraviroc and dofetilide, [ 16 , 17 ] dialkylphosphoric acid esters [ 18 ] and thiourea/urea compounds [ 19 ] have all been reported to undergo proton migration prior to fragmentation. Internal proton transfer to C‐3 of 4‐hydroxycourmarin is not thermodynamically favourable but is required to trigger bond cleavage.…”

Predicting collision-induced dissociation spectra: Semi-empirical calculations as a rapid and effective tool in software-aided mass spectral interpretation

“…Penicillin shows cleavage of the β‐lactam bond after transfer of the proton from the carbonyl to the lactam nitrogen . In addition, dibenzyl ethers, the pharmaceutical compound maraviroc, dialkylphosphoric acid esters and thiourea/urea compounds have all been reported to exhibit product ions in their mass spectra generated following proton migration from the most thermodynamically likely site. It has been proposed that the energy for proton migration is obtained by the transfer of kinetic to internal energy during ion molecule collisions, probably in the collision cell during CID.…”

Mass spectrometric studies on the in vitro generated metabolites of SIRT1 activating drugs for doping control purposes

“…The elimination of H 2 O from the hydroxylated quinoxaline residue resulted in the product ion at m/z 354. This fragmentation was observed only for the metabolite M1-SRT1720 (8) [46,47] Analogous to the metabolite M3-SRT1720 (10), the subsequent elimination of piperazine (C 4 (Fig. S6).…”