Cyclic dipeptides are relatively simple compounds that can exhibit a great variety of important biological activities. The fragmentation pathways of protonated cyclic dipeptides have been studied by electrospray ionization multistage mass spectrometry (ESI-MSn). The mass spectra studies of the cyclic dipeptides showed that the cyclic dipeptides with the similar substituents, the side chains of amino acid residues at the diketopiperazine ring, followed the same fragmentation pathway. In the fragmentation spectra of protonated cyclic dipeptides, some characteristic fragment ions were observed and could be used to distinguish the cyclic dipeptides. The hydrogen/deuterium (H/D) exchange experiment and the high-resolution mass spectrometry (Q-TOF) were used to verify and rationalize the proposed fragmentation pathways. These observations may have some potential applications in the structural elucidation and interpretation of the mass spectra of homologous compounds.

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.

The reaction of amino acids and phosphorus trichloride in THF was studied by 31 P NMR tracing and ESI-MS/MS. A series of hydridophoranes and cyclic dipeptides were obtained. The reaction presented interesting diversity and the reaction mechanism was proposed. The mechanism suggests that phosphorus plays an important role in the synthesis of amino acid hydridophorane and cyclic dipeptides. The results also show that 31 P NMR and ESI-MS/MS are useful tools for the investigation of reaction mechanism.