Novel product ions of 2-aminoanilide and benzimidazole Ag(I) complexes using electrospray ionization with multi-stage tandem mass spectrometry

GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709-3398, USA.
Rapid Communications in Mass Spectrometry (Impact Factor: 2.25). 05/2012; 26(9):1115-22. DOI: 10.1002/rcm.6210
Source: PubMed


The 2-aminoaniline scaffold is of significant value to the pharmaceutical industry and is embedded in a number of pharmacophores including 2-aminoanilides and benzimidazoles. A novel application of coordination ion spray mass spectrometry (CIS-MS) for interrogating the silver ion (Ag(+)) complexes of a homologous series of these compounds using multi-stage tandem mass spectrometry is described. Unlike the ubiquitous alkali metal ion complexes, Ag(+) complexes of 2-aminoanilides and benzimidazoles were found to yield [M - H](+) ions in significant abundance via gas-phase elimination of the metal hydride (AgH) resulting in unique product ion cascades.
Sample introduction was by liquid chromatography with mass spectrometry analysis performed on a hybrid linear ion trap/orbitrap instrument capable of high-resolution measurements.
Rigorous structural characterization by multi-stage tandem mass spectrometry using [M +  H](+), [M - H](-) and [M - H](+) precursor ions derived from ESI and CIS experiments was performed for the homologous series of 2-aminoanilide and benzimidazole compounds. A full tabular comparison of structural information resulting from these product ion cascades was produced.
Multi-stage tandem mass spectrometry of [M - H](+) ions resulting from Ag(+) complexes of 2-aminoanilides and benzimidazoles in CIS-MS experiments produced unique product ion cascades that exhibited complementary structural information to that obtained from tandem mass spectrometry of [M  +  H](+) and [M - H](-) ions by electrospray ionization (ESI). These observations may be broadly applicable to other compounds that are observed to form Ag(+) complexes and eliminate AgH.

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    • "[4] [23] [24] Metal complexation not only increases the ionization efficiency in ESI-MS, but also alters fragmentation pathways in MS n . [25] [26] [27] [28] [29] [30] [31] Many positional isomers [32] [33] [34] [35] [36] [37] [38] [39] and enantiomers [40] [41] [42] [43] [44] [45] have been successfully distinguished by comparing structurally distinctive product ions resulting from dissociation of metal complexes in MS n . "
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