Fragmentation of deprotonated cyclic dipeptides by electrospray ionization mass spectrometry

The fragmentation pathways of deprotonated cyclic dipeptides have been studied by electrospray ionization multi-stage mass spectrometry (ESI-MSn) in negative mode. The results showed that the fragmentation pathways of deprotonated cyclic dipeptides depended significantly on the different substituents, the side chains of amino acid residues at the diketopiperazine ring. In the spectra of deprotonated cyclic dipeptides, the ion [M-H-substituent radical]- was firstly observed in the ESI mode. The characteristic fragment ions [M-H-substituent radical]- and [M-H-(substituent-H)]- could be used as the symbols of particular cyclic dipeptides. The hydrogen/deuterium (H/D) exchange experiment, the high-resolution mass spectrometry (Q-TOF) and theoretical calculations were used to rationalize the proposed fragmentation pathways and to verify the differences between the fragmentation pathways. The relative Gibbs free energies (DeltaG) of the product ions and possible fragmentation pathways were estimated using the B3LYP/6-31++G(d, p) model. The results have some potential applications in the structural elucidation and interpretation of the mass spectra of homologous compounds and will enrich the gas-phase ESI-MS ion chemistry of cyclic dipeptides.