Differentiation of heterocyclic regioisomers: a combined tandem mass spectrometry and computational study of N-acridin-4-ylbenzylamide and N-acridin-2-yl-benzylamide.
Electrospray ionization (ESI) tandem mass spectrometry (MS/MS) has been used to differentiate two positional isomers of acridine derivatives, N-acridin-4-ylbenzylamide and N-acridin-2-ylbenzylamide. The study revealed that the isomeric ion structures produced by these heterocycles could be distinguished upon collision-induced dissociations (CID). In particular, the loss of a water molecule was shown to be a regiospecific reaction of the protonated N-acridin-4-ylbenzylamide, in which the location of the benzylamide substituent with respect to the acridinic nitrogen greatly assists proton migration by allowing the creation of intramolecular hydrogen bonds. To a lesser extent, the two isomers could also be distinguished by the difference in the abundance of the benzoyl cation in the MS/MS spectra of the [M+H]+ ions, as this ion is produced with a much higher rate from N-acridin-4-ylbenzylamide. Calculations based on quantum-mechanical models have been performed to evaluate the stability of the ion structures and to support mechanisms proposed for these two dissociation reactions.
Tintaru
Aura
A
Universités d'Aix-Marseille I, II & III CNRS, UMR 6264: Laboratoire Chimie Provence, Spectrométries Appliquées à la Chimie Structurale, 13397 Marseille, France.
Benchabane
Yohann
Y
Boyer
Gérard
G
Humbel
Stéphane
S
Charles
Laurence
L
D000166:Acridines / Q000032:analysis*; D001593:Benzyl Compounds / Q000032:analysis*; D003198:Computer Simulation; D007536:Isomerism; D008956:Models, Chemical; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013816:Thermodynamics
D000166:Acridines; D001593:Benzyl Compounds