Is the first step in MALDI in-source decay electron transfer or hydrogen atom abstraction?

Matrix-assisted laser desorption/ionization in-source decay (MALDI-ISD) with reducing matrices enables rapid mass spectrometric characterization of intact proteins. Several novel matrices have been developed for improving the fragmentation efficiency of MALDI-ISD. In particular, matrix having aniline group stronger facilitate MALDI-ISD than that having phenol group. Because the aniline N–H bond is stronger than the phenol O–H bond, the efficient fragmentation induced using matrices containing aniline group cannot be explained by the previously proposed mechanism involving the matrix-peptide hydrogen atom transfer. To explain these phenomena, electron transfer from the matrix to the peptide was recently proposed as the initial step in the MALDI-ISD processes. In this study, to estimate whether a peptide acquires hydrogen atoms or electrons in the first step of MALDI-ISD, the transition-state barriers of the reaction between dipeptide and hydrogen atoms produced from the excited-state matrix were calculated, assuming the peptide in the ground state during the MALDI-ISD process. The barrier obtained for the corresponding hydrogen atom attachment reaction did not correlate with the yield of the fragment ions produced by MALDI-ISD. In contrast, a correlation has been reported between the yields of the fragment ions produced by MALDI-ISD and the ionization energy of the matrix solids, indicating that MALDI-ISD occurs efficiently using a matrix that easily emits electrons. These results strongly suggest that MALDI-ISD of peptides using reducing matrices is well explained by the transfer of electrons and subsequent protons from the matrix to the peptide.