Novel product ions of 2-aminoanilide and benzimidazole Ag(I) complexes using electrospray ionization with multi-stage tandem mass spectrometry
ABSTRACT 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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- "   Metal complexation not only increases the ionization efficiency in ESI-MS, but also alters fragmentation pathways in MS n .        Many positional isomers         and enantiomers       have been successfully distinguished by comparing structurally distinctive product ions resulting from dissociation of metal complexes in MS n . "
ABSTRACT: RATIONALEDevelopment of mass spectrometry (MS)-based methods for isomeric differentiation remains a challenging analytical task, and has attracted the interest of many research groups. It is relevant to develop a general method to differentiate the isomeric halogenated phenylmethylidene hydrazinecarbodithioates (MX, X = F, Cl, Br).METHODS Diluted CH3CN solutions containing NiCl2 and a title isomer (MX) were analyzed by electrospray ionization tandem mass spectrometry (ESI-MSn) in a quadrupole ion trap instrument equipped with an ESI source. Theoretical calculations were performed using the density functional theory (DFT) method at the uB3LYP/6-31+G(2d,p) level.RESULTSIn MS3 experiments, the complex [MX + SCH3 + Ni]+ ion, resulting from dissociation of the ESI-generated complex [2MX – H + Ni]+ ion, undergoes ligand-exchange reactions with residual gas molecules, such as water, acetonitrile, and nitrogen in the ion trap, and the o-isomers [Mo-X + SCH3 + Ni]+ were found to undergo the characteristic HX elimination reactions to afford several unique ions. Each set of three isomers [MX + SCH3 + Ni]+ show significantly different reactivity, which has been corroborated by MS4 experiments and theoretical calculations.CONCLUSIONSA rapid method based on metal complexation and tandem mass spectrometric (MSn) analysis has been developed to differentiate three sets of positional isomers of halogenated phenylmethylidene hydrazinecarbodithioates (MX, X = F, Cl, Br). Copyright © 2014 John Wiley & Sons, Ltd.Rapid Communications in Mass Spectrometry 10/2014; 28(19). DOI:10.1002/rcm.6991 · 2.64 Impact Factor
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ABSTRACT: This paper reports here Nazarov cyclization and oxo-Diels–Alder reaction induced by the naked silver cation in the collisional activation of silver(I)/chalcone complexes, which lead to the final elimination of AgOH and AgH, respectively. Deuterium labeling experiments, DFT calculations, and the substituent effect were utilized to confirm the reaction mechanisms.Organometallics 05/2013; 32(11):3385–3390. DOI:10.1021/om4003285 · 4.25 Impact Factor
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ABSTRACT: In collisional activation of argentinated N-arylmethyl-pyridin-2-ylmethanimine, a neutral molecule of AgNH2 is eliminated, carrying one hydrogen from the methylene and the other one from the ortho position (relative to the ipso carbon) of the aryl ring. Taking argentinated N-benzyl-pyridin-2-ylmethanimine for example, the proposition that the AgNH2 loss results from intramolecular arylmethyl transfer combined with cyclodeamination is rationalized by deuterium labeling experiments, blocking experiments, and theoretical calculations. The structure of the final product ion from loss of AgNH2 was confirmed further by multistage mass spectrometry.Journal of the American Society for Mass Spectrometry 12/2013; 25(2). DOI:10.1007/s13361-013-0778-7 · 3.19 Impact Factor