Protonation sites in peptide dications and cation-radicals containing β-amino acid residues

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Protonation sites in a model pentapeptide Ala-Ala-βAb-Ala-Ala, where βAb was β-aminobutyric acid, were studied by ab initio and density functional theory calculations. Gas-phase dication tautomers protonated at the N-terminus and amide oxygens were found to be substantially more stable than tautomers protonated at amide nitrogens. This order of ion stability did not change upon solvation with methanol. Conformational analysis of dication tautomers indicated similar degrees of internal solvation by hydrogen bonding in amide O- and N-protonated ions in the gas phase. Because of the low stability of amide N-protonated tautomers, their formation by electrospray of non-basic peptides is highly unlikely. Computational analysis of Ala-Ala-βAb-Ala-Ala cation-radicals indicated substantially lower transition-state energies for NCα bond dissociations at Ala residues than for the NCβ bond dissociation at βAb. The formation of β-radicals as z fragments was found to require a high threshold energy. Cleavage of the CONH2 bond leading to b and y fragments was hampered by a high-energy transition state for the formation of an N-protonated cation-radical intermediate as well as by a high threshold energy for the fragment formation. The calculated energies for transition states and dissociation thresholds explain the less efficient NCβ bond dissociation upon electron capture or transfer in peptide ions containing β-amino acid residues.