Transition metal ions: charge carriers that mediate the electron capture dissociation pathways of peptides.

Electron capture dissociation (ECD) of model peptides adducted with first row divalent transition metal ions, including Mn(2+), Fe(2+), Co(2+), Ni(2+), Cu(2+), and Zn(2+), were investigated. Model peptides with general sequence of ZGGGXGGGZ were used as probes to unveil the ECD mechanism of metalated peptides, where X is either V or W; and Z is either R or N. Peptides metalated with different divalent transition metal ions were found to generate different ECD tandem mass spectra. ECD spectra of peptides metalated by Mn(2+) and Zn(2+) were similar to those generated by ECD of peptides adducted with alkaline earth metal ions. Series of c-/z-type fragment ions with and without metal ions were observed. ECD of Fe(2+), Co(2+), and Ni(2+) adducted peptides yielded abundant metalated a-/y-type fragment ions; whereas ECD of Cu(2+) adducted peptides generated predominantly metalated b-/y-type fragment ions. From the present experimental results, it was postulated that electronic configuration of metal ions is an important factor in determining the ECD behavior of the metalated peptides. Due presumably to the stability of the electronic configuration, metal ions with fully-filled (i.e., Zn(2+)) and half filled (i.e., Mn(2+)) d-orbitals might not capture the incoming electron. Dissociation of the metal ions adducted peptides would proceed through the usual ECD channel(s) via "hot-hydrogen" or "superbase" intermediates, to form series of c-/z(•)- fragments. For other transition metal ions studied, reduction of the metal ions might occur preferentially. The energy liberated by the metal ion reduction would provide enough internal energy to generate the "slow-heating" type of fragment ions, i.e., metalated a-/y- fragments and metalated b-/y- fragments. © American Society for Mass Spectrometry, 2011