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

RATIONALE 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. METHODS Sample introduction was by liquid chromatography with mass spectrometry analysis performed on a hybrid linear ion trap/orbitrap instrument capable of high‐resolution measurements. RESULTS 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. CONCLUSIONS 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. Copyright © 2012 John Wiley & Sons, Ltd.