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

Fragmentation reactions of thiourea- and urea-compounds, which are promising reagents for chemical crosslinking (XL), are investigated in detail by collision-induced dissociation (CID) experiments in a quadrupole ion trap (QIT), energy-resolved CID experiments, and computational modeling. For this study, an array of six labeled and unsymmetrical substituted thiourea- and urea-derivatives were synthesized, which allow unambiguous characterization of competing fragmentation pathways. The results of the QIT-CID-experiments are explored in detail for two compounds and confirmed by results for the other four. These results document the subtle competition of characteristic fragmentation pathways of this class of compounds. The multi dimensional investigations of the characteristic fragmentation reactions allow reliable structure proposals of prominent product ions. Energy-dependent CID experiments on two of the six compounds lead to breakdown curves that show similar relative threshold energies for the formation of the product ions on which the functioning of the XL application relies. The experimental results are in full consistency with the results from in-depth computations. For the dominant fragmentations observed, the transition states for moving the proton from the most basic site of the precursor ion (the thiourea-sulphur or the urea carbonyl oxygen) to less basic heteroatoms in the protonated molecular ion is the necessary and decisive step that determines the extent of the charge-driven fragmentation processes that follow.