Gas‐phase fragmentation study of novel synthetic 1,5‐benzodiazepine derivatives using electrospray ionization tandem mass spectrometry

Abstract

The fragmentation patterns of a series of three novel synthesized 3-hydroxy-4-phenyl-tetrahydro-1,5-benzodiazepin-2-ones (1-3), possessing the same backbone structure, were investigated using electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (MS/MS) techniques. A simple methodology, based on the use of ESI (positive ion mode) and by increasing the declustering potential in the atmospheric pressure/vacuum interface, collision-induced dissociation (CID), was used to enhance the formation of the fragment ions. In general, the novel synthetic 1,5-benzodiazepine derivatives afforded, in the gas phase, both protonated and sodiated molecules. This led to the confirmation of the molecular masses and chemical structures of the studied compounds. Exact accurate masses were measured using a high-resolution ESI-quadrupole orthogonal time-of-flight (QqToF)-MS/MS hybrid mass spectrometer instrument. The breakdown routes of the protonated molecules were rationalized by conducting low-energy collision CID-MS/MS analyses (product ion- and precursor ion scans) using a conventional quadrupole-hexapole-quadrupole (QhQ) tandem mass spectrometer. All the observed major fragmentations for the 1,5-benzodiazepines occurred in the saturated seven-membered ring containing the nitrogen atoms. These formed a multitude of product ions by different breakdown routes. All the major fragmentations involved cleavages of the N-1-C-2 and C-3-C-4 bonds. These occurred with concomitant eliminations of glyoxal, benzene and ethyl formate, forming the product ion at m/z 119, which was observed in all the studied compounds. In addition, an unique simultaneous CID-MS/MS fragmentation was noticed for the 1,5-benzodiazepines 1 and 3, which occurred by a pathway dictated by the substituent located on the N-1-position. It was evident that the aromatic ring portion of the 1,5-benzodiazepines was resistant to CID-MS/MS fragmentation. Re-confirmation of the various geneses of the product ions was achieved by conducting a series of precursor ion scans. ESI-MS and CID-MS/MS analyses have thus proven to be a specific and very sensitive method for the structural identification of these novel 1,5-benzodiazepine derivatives.

Novel efficient fluorophores synthesized from citric acid

“…Moreover, the combination of HR-LCMS data with fragmentation spectra of molecular ions have been frequently reported as a sufficient method for structure elucidation of peptides, biomolecules as well as small molecules and metabolites. 39,40 The S-CAFM group has been represented in the literature up to now only by CAFM synthesized in the presence of (2a), (4a) and glutathione (6a). [16][17][18]26,31 Herein we conrmed that (2b) can be easily fabricated through condensation reaction of CA and (2a).…”

Spectral trends in GC-EI-MS data obtained from the SWGDRUG mass spectral library and literature: A resource for the identification of unknown compounds

“…Ions at m/z 75 and m/z 77 are observed across the RA categories bins (Table 3) and can be explained by fragmentation at the phenyl ring and the R4 group [31,32]. The Medium RA category consists of ions generated from the fragmentation and recombination of the remaining core structure which can be found in numerous reports [30,[33][34][35][36]. Ions at m/z…”

Gas‐phase fragmentation study of biotin reagents using electrospray ionization tandem mass spectrometry on a quadrupole orthogonal time‐of‐flight hybrid instrument

“…In a continuation of our research work on the gas‐phase MS fragmentation of novel biomolecules,25–29 we present herein the ESI‐MS and CID‐MS/MS fragmentations of the five different biotin linkers 1 – 5 .…”