Difference of Electron Capture and Transfer Dissociation Mass Spectrometry on Ni(2+)-, Cu(2+)-, and Zn(2+)-Polyhistidine Complexes in the Absence of Remote Protons

Abstract

Electron capture dissociation (ECD) and electron transfer dissociation (ETD) in metal-peptide complexes are dependent on the metal cation in the complex. The divalent transition metals Ni(2+), Cu(2+), and Zn(2+) were used as charge carriers to produce metal-polyhistidine complexes in the absence of remote protons, since these metal cations strongly bind to neutral histidine residues in peptides. In the case of the ECD and ETD of Cu(2+)-polyhistidine complexes, the metal cation in the complex was reduced and the recombination energy was redistributed throughout the peptide to lead a zwitterionic peptide form having a protonated histidine residue and a deprotonated amide nitrogen. The zwitterion then underwent peptide bond cleavage, producing a and b fragment ions. In contrast, ECD and ETD induced different fragmentation processes in Zn(2+)-polyhistidine complexes. Although the N-Cα bond in the Zn(2+)-polyhistidine complex was cleaved by ETD, ECD of Zn(2+)-polyhistidine induced peptide bond cleavage accompanied with hydrogen atom release. The different fragmentation modes by ECD and ETD originated from the different electronic states of the charge-reduced complexes resulting from these processes. The details of the fragmentation processes were investigated by density functional theory. Graphical Abstract ᅟ.

Keywords: Density functional theory calculation; Hydrogen radical loss; Metal reduction; Peptide bond cleavage; Zwitterion formation.