During our ongoing investigation of the formation and reactivity of gas-phase complex ions composed of Ag(I) and various R-amino acids, we discovered that the mass-to-charge ratio for the major collision-induced dissociation (CID) product generated from a binary Ag + complex with phenylalanine was consistent with the formation of an Ag + complex with an aldehyde. In this study we investigated and compared the fragmentation pathways for complexes of Ag + with phenylalanine, phenylalanine with exchangeable protium replaced with deuterium, phenylalanine with the carboxylic acid group labeled with 13 C, and phenylalanine with the benzylic group labeled with deuterium. The reaction pathways were determined using multidimensional dissociation steps in an ion-trap mass spectrometer. The dissociation experiments provide clear evidence for the formation of several novel product species, including the Ag + complex with phenylacetaldehyde, as well as the formation of an Ag + complex with either a benzyl carbene or styrene. These dissociation products are markedly different from those observed following the fragmentation of other transition and alkali metal adducts of phenylalanine. On the basis of the dissociation of the various isotope-exchanged and -labeled versions of phenylalanine, we propose several reaction pathways that implicate the formation of an Ag + complex with an aziridinone (Rlactam), for which a peak at the correct mass-to-charge ratio was observed in the MS/MS spectrum of the (M + Ag) + ion. A comparison of the apparent reactivity toward water and methanol in the ion-trap mass spectrometer of the Ag + -containing product ions to Ag + complexes with various low-mass organic molecules provided further evidence to support the proposed formation of the aldehyde and styrene complexes with Ag + ions. For instance, the apparent reactivity of the Ag + /aldehyde product ion generated from the CID of the (M + Ag) + ion is identical to that observed for a complex produced by the electrospray ionization of a solution containing Ag + ions and neat phenylacetaldehyde. Similar results were obtained for a dissociation product ion assumed to be a complex composed of Ag + ions and styrene.

In a previous report we showed that certain binary Ag(+)-amino acid complexes formed adduct ions by the attachment of a single water and methanol molecule when stored in an ion trap mass spectrometer: complexes with aliphatic amino acids and with 4-fluorophenylalanine formed the adduct ions whereas complexes with phenylalanine and tryptophan did not. In this study we compared the tendency of the Ag(+) complexes derived from phenylalanine, 4-fluorophenylalanine, 4-hydroxyphenylalanine (tyrosine), 4-bromophenylalanine, 4-nitrophenylalanine and aminocyclohexanepropionic acid to form water adducts when stored, without further activation, in the ion trap for times ranging from 1 to 500 ms. Because the donation of pi electron density to the Ag(+) ion is a likely determining factor in complex reactivity, our aim in the present study was to determine qualitatively the influence of para-position substituents on the aromatic ring on the formation of the water adducts. Our results show that the reactivity of the complexes is influenced significantly by the presence of the various substituents. Decreases in [M + Ag](+) ion abundance, and increases in adduct ion abundance, both measured as a function of storage time, follow the trend -NO(2) > -Br > -F > -OH > -H. The complex of Ag(+) with 4-nitrophenylalanine was nearly as reactive towards water as the Ag(+) complex with aminocyclohexanepropionic acid, the last being an amino acid devoid of pi character in the ring system. Collision induced dissociation of the [M + Ag](+) species derived from the amino acids produces, among other products, Ag(+) complexes with a para-substituted phenylacetaldehyde: complexes that also form adduct species when stored in the ion trap. The trends in adduct ion formation exhibited by the aldehyde-Ag(+) complex ions were similar to those observed for the precursor complexes of Ag(+) and the amino acids, confirming the influence of the ring substituent.

We compared the tandem mass spectra of a range of native and acetylated Ag(+) cationized peptides to determine the influence of the derivatization step on the abundance of the [b(n) + 17 + Ag](+) product ions. Using tripeptides, the smallest for which the mechanisms to generate [b(2) - 1 + Ag](+) and [b(2) + 17 + Ag](+) products are both operative, we found that in most cases acetylation causes an increase in the abundance of the C-terminal rearrangement ion, [b(2) + 17 + Ag](+), relative to the rival N-terminal rearrangement ion, [b(2) - 1 + Ag](+). The presence of a free amino group to bind to the metal ion significantly influences the relative abundances of the product ions. We propose a mechanism for the formation of the [b(n) + 17 + Ag](+) that is based on the formation of a five-membered oxazolidin-5-one and tetrahedral carbon intermediate that may collapse to a peptide upon release of CO and an imine, aided by the fact that the ring formed during C-terminal rearrangement is both a hemiacylal and hemiaminal. We also identified an influence of amino acid sequence on the relative abundances of the [b(n) + 17 + Ag](+) and [b(n) - 1 + Ag](+) product ions, whereby bulky substituents located on the alpha-carbon of the amino acid to the C-terminal side of the cleavage site apparently promote the formation of the [b(n) + 17 + Ag](+) product over [b(n) - 1 + Ag](+) when the amino acid to the N-terminal side of the cleavage site is glycine. The latter ion is the favored product, however, when the bulky group is positioned on the alpha-carbon of the amino acid to the N-terminal side of the cleavage site.