Nanosolvation by acetonitrile and 18-crown-6 ether induce strongly different effects on the electron-capture induced dissociation of aromatic tripeptide cations in the gas phase

Experimental gas-phase Electron Capture-Induced Dissociation (ECID) coupled to mass-spectrometry has been performed on the doubly-protonated tripeptides Lys-Trp-Lys (KWK) and Lys-Tyr-Lys (KYK). In this report, we focus on the influence of non-covalent binding of two different molecules, acetonitrile and 18-crown-6 ether (CE), to these tripeptide cations on the relative probabilities of their main fragmentation channels (H loss, NH3 loss and NCα bond cleavage) after electron capture from sodium atoms. First, we recorded the spectra of bare peptide ions, and found that NCα bond cleavage leads to fragments containing the aromatic amino acid. The structures and energies of the low-lying conformers of the tripeptide dications and radical monocations obtained from our DFT and MP2 calculations are in line with this observation. Second, the ECID spectra of KWK and KYK dications nanosolvated by one and two molecules show that acetonitrile evaporation is almost complete a few microseconds after electron capture, whereas fragments nanosolvated by CE are abundant. This is consistent with the binding energy of these molecules to lysine-containing peptides, which is much higher for CE than for acetonitrile. One or two acetonitrile molecules have also been found to induce little effect on the fragmentation patterns of the charge-reduced peptide ions. By contrast, one or two CE decreases the NH3-loss probability, which is accounted for by the inhibition of this channel upon CE binding to the N-terminal ammonium group. Besides, this experimental result is consistent with our DFT calculations, which suggest a lower abundance of N terminally-protonated [KWK+2H]2+(CE)2 compared to bare tripeptide cations. Extracting the H-loss contribution from ECID data had never been done for tripeptides nanosolvated by CE. This allowed us to observe the enhancement of H loss from KWK and KYK nanosolvated by two CE, but surprisingly, not by one. This peculiar behavior might be due to H transfer from the reduced radical NH3 group to CE, followed by loss of the [CE+H] radical.

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► Electron Capture-Induced Dissociation of nanosolvated aromatic tripeptide cations has been performed.
► Molecular dynamics, DFT and MP2 calculations have been carried out.
► Acetonitrile non-covalent binding has a very minor effect on their fragmentation patterns.
► 18-crown-6 ether non-covalent binding has a strong effect on the main fragmentation channel probabilities.