Formation of molecular radical cations of aliphatic tripeptides from their complexes with Cu^II(12‐crown‐4)

Abstract

Molecular radical cations have proven to be difficult to generate from aliphatic peptides under electrospray ionization mass spectrometry (ESI-MS) conditions. For a family of small aliphatic peptides GGX, where X = G, A, P, I, L and V, these cations have been generated by electrospraying a mixture of Cu.2+, 12-crown-4 and GGX in methanol/water. GGX.+ is readily formed from the collision-induced dissociation (CID) of [CuII(12-crown-4)(GGX)].2+. The formation of these aliphatic peptide radical ions from these complexes, in cases where it is not possible from the corresponding complexes involving a series of amine ligands instead of 12-crown-4, is likely due to the second ionization energy of the [CuI(12-crown-4)(GGX)]+ complex being higher than that of the corresponding [CuI(amine)(GGX)]+ complex. Using these 12-crown-4 complexes, GGI can be differentiated from the isomeric GGL by comparing the CID spectra of their [a3 + H].+ ions.

Fragmentation of Singly, Doubly, and Triply Charged Hydrogen Deficient Peptide Radical Cations in Infrared Multiphoton Dissociation and Electron Induced Dissociation

“…A frequently used method for generation of hydrogen deficient species is based on low energy CID of ternary metal complexes containing an auxiliary ligand (L) and the peptide or amino acid (M), [Metal(L)M] n+ [15][16][17][18][19][20][21][22][23][24][25][26]. Under low energy CID, dissociation of the [Metal(L)M] n+ complex is observed and the metal-auxiliary ligand system removes an electron from the departing peptide resulting in the generation of the hydrogen deficient species [18,21,27].…”

“…Furthermore, the metal ion used, the peptide composition and the presence of specific amino acids, Tyr, Trp, Arg, Lys, His in the polypeptide also play a significant role in the generation of these radical cations [15-17, 27, 30, 32]. It should be pointed out that regardless of the metal ion and the auxiliary ligand used, the presence of both a basic, Arg, His, Lys, and an aromatic Trp or Tyr amino acid residue facilitate the formation of the [M + nH] (n+1)+· species [15][16][17][18][19][20]. In addition to the investigations focusing on the generation of hydrogen deficient peptide radical cations, several reports have focused on their gas phase dissociation, mainly in CID [11,21,[27][28][29][32][33][34][35][36][37][38][39][40][41][42].…”

Kinetics for tautomerizations and dissociations of triglycine radical cations

“…UV photodissociation of a peptide/protein chemically modified to incorporate an appropriate chromophore can generate a radical cation that undergoes site-specific, radical-driven dissociations, which are useful in protein identifications [25,26]. Peptide radical cations have also been generated via low-energy CID of a ternary metal complex containing the peptide and auxiliary ligands [27][28][29][30][31][32][33][34][35][36][37]. These methodologies open new avenues whereby the fragmentation chemistries of peptide radical cations can be examined and exploited.…”

Experimental and computational studies of the macrocyclic effect of an auxiliary ligand on electron and proton transfers within ternary copper(II)-Histidine complexes

“…Oxidized radical products from Cu(II)-protein ion complexes have been proposed as intermediates that play key roles in several neurodegenerative conditions, including Alzheimer's disease (␤-amyloid peptide) and bovine spongiform encephalitis (prion protein) [3,4]. It was demonstrated recently that the dissociation of ligated Cu(II)-peptide complexes [Cu II (L)M] •2ϩ (L, ligand; M, peptide) generates peptide radical cations (M •ϩ ) through ET dissociation in the gas phase [7][8][9][10][11][12][13][14][15][16][17][18]. Such complexes are a useful simple system for studying the fundamental parameters that govern the formation of peptide radical cations through single-electron transfer in the absence of solvation.…”

“…The experimental results can be further examined in conjunction with theoretical calculations. Several systematic studies have been performed to determine the roles played by the auxiliary ligands and metals during the formation of peptide radical cations through ET dissociation (Reaction 1) [7][8][9][10][11][12][13][14][15][16]. Three major competitive dissociation pathways have been reported: proton transfer (PT) to the peptide (Reaction 2) [7-12, 14, 16, 19 -21], proton abstraction from the peptide (Reaction 3) [7,8,10,11,22], and peptide fragmentation (Reaction 4) [7-12, 14, 19, 20, 23, 24].…”