Interactions of peptides with simple Lewis acids and fragmentation mechanisms of adducts studied by tandem mass spectrometry

The dissociations of [Cu(II)AA(AA-H)]+ complexes with the amino acids (AA) Gly, Ala, Val, Leu, Ile, t-Leu, and Phe (no heteroatoms in the side chain) have been examined in the gas phase by tandem mass spectrometry (MS/MS), using collisionally activated dissociation (CAD) in an electrospray ionization ion trap mass spectrometer. These complexes contain an intact and a deprotonated AA ligand. The amino groups of both AA units, the carbonyl group of the intact amino acid, and the deprotonated hydroxyl oxygen coordinate Cu(II) in square-planar fashion. Under CAD conditions, the [Cu(II)AA(AA-H)]+ complexes undergo decarboxylation with simultaneous reduction of Cu(II) to Cu(I); during this process, a radical site is created at the alpha-carbon of the decarboxylated ligand (N1H2·C alphaHCbetaH2R). The radical site is able to move along the backbone of the decarboxylated amino acid to form two new radicals (·N1HCalphaH2Cbeta H2R and/or N1H2CalphaH 2·CbetaHR). From the complex of t-Leu, only Calpha and N1 radicals can be formed. The whole radical ligand can be lost to form [Cu(I)AA]+ from these three isomeric radicals. Alternatively, further radical induced dissociations can take place along the backbone of the decarboxylated amino acid ligand to yield [Cu(II)AA(AA-H2-CO2)]+, [Cu(I)AA(·NH 2)]+, and/or [Cu(I)AA(NH=CalphaH2)] +. Those products may undergo consecutive dissociation to form the final product [Cu(I)AA]+. The sodiated copper complexes ([Cu(II)(AA-H+Na)(AA-H)] +) show the same fragmentation patterns as their non-sodiated counterparts; sodium ion is retained on the intact amino acid ligand and is not involved in the CAD pathways. On the basis of the CAD spectra, reasonable dissociation mechanisms are proposed for the [Cu(II)AA(AA-H)]+ complexes and substantiated by calculated potential energy diagram of selected CAD channels of the [Cu(II)Ala(Ala-H)]+ complex.; For copper complexes with amino acids with aliphatic or phenyl side chains, only the deprotonated amino acid ligand is involved in the dissociation reactions. On the other hand, complexes of copper and amino acids with functionalized side-chains additionally undergo inter-ligand reactions. As the size of the molecules coordinated to copper increases, the probability of inter-ligand reactions increases. (Abstract shortened by UMI.)...