Recognition and resolution of isomeric alkyl anilines by mass spectrometry

Abstract

Two MS techniques have been used to recognize and resolve a representative isomeric pair of N-alkyl and ring-alkyl substituted anilines. The first technique (1) uses MS/MS to perform ion/molecule reactions of structurally-diagnostic fragment ions (SDFI) whereas the second (2) uses traveling wave ion mobility spectrometry (TWIMS) of the pair of protonated molecules followed by on-line collision-induced dissociation (CID), that is, MS/TWIMS-CID/MS. Isomeric C 7 H 7 N ϩ ions of m/z 106 (1= from 4-butylaniline and 2 from N-butylaniline) are formed as abundant fragments by 70 eV EI of the anilines, and found to function as suitable SDFI. Ions 1= and 2 display nearly identical unimolecular dissociation chemistry, but contrasting bimolecular reactivity with ethyl vinyl ether, isoprene, acrolein, and 2-methyl-1,3-dioxolane. Ion 2 forms adducts to a large extent whereas 1= is nearly inert towards all reactants tested. The intact protonated anilines are readily resolved and recognized by MS/TWIMS-CID/MS in a SYNAPT mass spectrometer (Waters Corporation, Manchester, UK). The protonated N-butyl aniline (the more compact isomer) displays shorter drift time and higher lability towards CID than its 4-butyl isomer. The general application of SDFI 1= and 2 and other homologous and analogous ions and MS/TWIMS-CID/MS for absolute recognition and resolution of isomeric families of N-alkyl and ring-alkyl mono-substituted anilines and analogues is discussed. somers have distinct structures and properties, but exactly the same mass. Mass spectrometry measures primarily mass; hence when dealing with intact gaseous species, MS is inherently blind for distinguishing isomers. Many MS strategies based on the correlation between structure and physicochemical properties, such as those exploring uni-or bimolecular reactivity, have therefore been developed to recognize and resolve gaseous isomeric ions [1]. Isomers sometimes display, however, very similar gaseous reactivities and still end up being indistinguishable by these approaches. Isomers have also been treated in case by case approaches and, up to now, no general MS strategy for isomer recognition and resolution is available.We have recently proposed a MS/MS strategy for wide-ranging, absolute (noncomparative) recognition and resolution of constitutional isomers based on structurally diagnostic fragment ions (SDFI) [2]. The main SDFI requisites are that they must: (1) be a fragment ion shared by most (ideally by all) members of the isomeric family; (2) contain and retain the structural information of its specific isomeric precursor; (3) be stable gaseous species with relatively high barriers for structural rearrangements, and (4) display contrasting dissociations or bimolecular reactivities, or both, induced and properly rationalized in terms of their distinct structures.Although the task is by no means easy, we have so far succeeded in finding several proper SDFI for different families of constitutional isomers. For instance, pyridinium ions function as SDFI for ortho, meta and para-s...

Baseline resolution of isomers by traveling wave ion mobility mass spectrometry: investigating the effects of polarizable drift gases and ionic charge distribution

“…The two isomers N ‐butylaniline and para ‐butylaniline are also challenging in terms of IM separation for the TWIM device, since the theoretical Ω He for their protonated molecules only differ by 1.5% (1.2 Å 2 ; Table ). TWIM‐MS in N 2 at a pressure of 1.0 mbar has been previously shown to resolve these isomers with a reasonable R p‐p of 0.71 . Herein, we first tested the limits of R p‐p improvement for isomers N ‐butylaniline and para ‐butylaniline using various drift‐gas pressures (Table ).…”

Analyzing complex mixtures of drug-like molecules: Ion mobility as an adjunct to existing liquid chromatography-(tandem) mass spectrometry methods

“…for detection of narcotics and explosives [7,8]. Although its hyphenation with MS in commercial instrumentation is a more recent development, it has already created new possibilities for the characterization of some classes of small molecules and metabolites [9][10][11]. Specific examples are the separation of isomeric disaccharides [12][13][14] and metal(-ligand) complexes [15][16][17] or the characterization of carbohydrate, glycan and lipid structures [18][19][20][21][22][23].…”

Exploring the coordination chemistry of isomerizable terpyridine derivatives for successful analyses of cis and trans isomers by travelling wave ion mobility mass spectrometry

“…Several IMS configurations have already been employed to separate structural isomers, such as field asymmetric waveform (FAIMS), tandem differential mobility analysis (TDMA) and traveling wave ion mobility (TWIM); [1][2][3][4][5] but, to the best of our knowledge, no report on the use of IMS in the study of cis-trans photoisomerization has yet been published.…”