Synchrotron vacuum ultraviolet (VUV) photo-induced fragmentation of cyclic dipeptides radical cations

Abstract

Cyclic dipeptides, due to their chemical properties and various bioactivities, are very attractive for medicinal chemistry. Fragmentations of three simple cyclic dipeptides including cyclo(Gly-Gly), cyclo(Ala-Ala) and cyclo(Gly-Val) in the gas-phase are determined with synchrotron vacuum ultraviolet (VUV) photoionization mass spectrometry (VUV PIMS) and theoretical calculations. Cyclo(Gly-Gly) and cyclo(Ala-Ala) show the similar fragmentation pathways. The primary decomposition reactions of cyclo(Gly-Gly) and cyclo(Ala-Ala) radical cations are found to be HNCO loss and CO elimination. The appearance energies (AEs) of fragment ions [CH2NHCOCH2]+• and [CH3CHNHCOCHCH3]+• are measured to be 10.21 and 9.66±0.05 eV, respectively, which are formed from cyclo(Gly-Gly) and cyclo(Ala-Ala) radical cations with HNCO elimination. Due to the stabilization of the radical cation of cyclo(Gly-Val) with isopropyl side group, the dominant fragment ion m/z 114 assigned as [C4H6N2O2]+• is produced by γ-H migration and i cleavage to lose propylene. The ionization energies (IEs) of three cyclic dipeptides decrease in the order cyclo(Gly-Gly) (9.33±0.05 eV)>cyclo(Ala-Ala) (9.21±0.05 eV)>cyclo(Gly-Val) (9.09±0.05 eV) from measurements of photoionization efficiency spectra. It implies that IEs of cyclic dipeptides are affected by substituent groups and symmetrical characterization of molecular structures. These observations of the chemical properties of cyclic dipeptides radical ion (M+•) may be important for understanding gas-phase molecular reactivity of 2,5-diketopiperazines and guiding diketopiperazine-based drug design.

Photofragmentation specificity of photoionized cyclic amino acids (diketopiperazines) as precursors of peptide building blocks

“…At variance with the fragmentation of amino acids, DKP derivatives have attracted less attention. Zhang et al 11 reported the VUV photoinduced fragmentation of cyclo(alanyl-alanine), cyclo(glycyl-glycine) and cyclo(glycilvaline) up to 11 eV, while the fragmentation of a series of both protonated and deprotonated cyclo-dipeptides has been studied by Guo et al 12,13 . We have recently shown 9 that the VUV irradiation of cyclo(alanyl-alanine), cAA, a 2,5-DKP with two methyl groups as side chains, produces oxazolidinone intermediates as well as being an excellent source of CO and HNCO prebiotic species.…”

“…9,10 At variance with the fragmentation of amino acids, DKP derivatives have attracted less attention. Zhang et al 11 reported the VUV photoinduced fragmentation of cyclo(alanyl-alanine), cyclo(glycyl-glycine) and cyclo(glycil-valine) up to 11 eV, while the fragmentation of a series of both protonated and deprotonated cyclo-dipeptides has been studied by Guo et al 12,13 We have recently shown 9 that the VUV irradiation of cyclo(alanyl-alanine) (cAA), besides being an excellent source of CO and HNCO prebiotic species can also produce oxazolidinone intermediates. In the same study, we proposed a model where the interaction among the oxazolidinone intermediate and other neutral and charged fragments released in the molecular decomposition of cAA + may lead either to the reconstruction of the cyclic cationic dipeptide or to the formation of longer linear peptide chains via almost barrierless processes, thus proposing a new mechanism for the formation of more complex biomolecules as oligo-peptides.…”