title: A study of fragmentation of protonated amides of some acylated amino acids by tandem mass spectrometry: observation of an unusual nitrilium ion.
abstract: A tandem mass spectrometric study of a series of secondary amides of acetylglycine and hippuric acid utilizing electrospray ionization (ESI) was conducted. Among the fragment ions observed was an unusual one, which we have determined to be a nitrilium ion having the structure CH3-C≡N⊕-Ph or Ph-C≡N⊕-Ph by loss of the full mass of glycine as a neutral fragment. A mechanism that we propose involves an initial protonation of the oxygen atom at the N-terminus, followed by cyclization to a five-membered imidazolium ring, and its subsequent collapse to the nitrilium ion. This mechanism is supported by extensive isotopic labels and considerable variation of substituents. A similar study of the amides of acyl β-alanine and acyl γ-aminobutyric acid revealed that the former furnishes the same nitrilium ion, but not the latter. Thus, a six-membered intermediate is also possible and capable of losing the full mass of β-alanine as a neutral fragment. When the size of the ring is forced to be seven-membered, this pathway is blocked. When this study was expanded to include a variety of N-acylproline amides, the nitrilium ion was observed in 100% abundance only when the acyl group was acetyl. Thus a proline effect (involvement of a strained bicyclic [3.3.0] structure) is being observed.
authors.affiliation: Department of Chemistry, Wichita State University, Wichita, KS 67260-0051, USA. erach.talaty@wichita.edu
authors.forename: Erach R
authors.initials: ER
authors.lastname: Talaty
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Young
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Dain
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Van Stipdonk
mesh_terms: D000215:Acylation; D000577:Amides / Q000737:chemistry*; D000596:Amino Acids / Q000737:chemistry*; D055598:Chemical Phenomena; D041961:Deuterium Exchange Measurement; D009570:Nitriles / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000577:Amides; D000596:Amino Acids; D009570:Nitriles