The effect of protonation site on bond strengths in simple peptides: Application of Ab initio and modified neglect of differential overlap bond orders and modified neglect of differential overlap energy partitioning

Abstract

A comparative study of ab initio 6-31G(*) and semiempirical modified neglect of differential overlap (MNDO) bond orders and MNDO diatomic energy contributions for the description of bond strengths in neutral and protonated glycine, diglycine, triglycine, and dialanine is presented. Good correlations were found between 6-31G(*) and MNDO bond orders and between MNDO bond orders and diatomic energy contributions. Although bond orders and diatomic energy contributions are inherently different quantities, both predict the changes in bond strengths due to protonation to be qualitatively the same. The theoretically predicted differences in bond strengths for different protonated forms clearly indicate that in peptide fragmentation schemes one should consider even those protonated forms whose formation is not preferred energetically.

The mobile proton hypothesis in fragmentation of protonated peptides: A perspective

“…First, relatively simple bond order calculations clearly indicated that the amide bond order (or, somewhat imprecisely, the amide bond strength) was much lower (weaker) in amide-N-protonated forms than in amide-O-protonated forms [12,20]. These calculations also implied that even though the amide-O-protonated forms are more stable energetically, they do not necessarily (or exclusively) trigger amide bond fragmentation.…”

“…Besides experimental studies, theoretical (quantum chemical) calculations have also played a role in the development of the mobile proton model [12,20,21]. First, relatively simple bond order calculations clearly indicated that the amide bond order (or, somewhat imprecisely, the amide bond strength) was much lower (weaker) in amide-N-protonated forms than in amide-O-protonated forms [12,20].…”

MALDI In-Source Decay, from Sequencing to Imaging

“…Because this thermal process is caused by vibrational activation of closed valence shell ions, the fragmentation mechanism can be explained by the "mobile proton" model [34]. These fragments are the result of the cleavage of the CO-NH bond that is weakened by the protonation of the nitrogen of the amide group [35,36]. The CID-like fragments (a-, b-, and y-type) can then be favored by the acidity of the matrix.…”

Proton affinity and enthalpy of formation of formaldehyde

“…T hough it is not the only factor, it is well established [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] that proton migration is crucial in inducing fragmentation in tandem mass spectrometry (MS/MS) experiments. The ease or difficulty of proton migration depends on the proton affinity (PA) [or the related gas-phase basicity (GB)] values of the protonation sites.…”