Studying On The Fragmentation Reaction Of N-Aryl Lactams In Electrospray Ionization Mass Spectrometry

Lactam framework is an important scaffold of lots of natural bioactive molecules. Appling the electrospray ionization high-energy collisional dissociation mass spectrometry to investigate the gas phase dissociation reactions of N-aryl lactam compounds is useful for their structural identification, structure-activity relationship and metabolic research. In this thesis, electrospray ionization tandem mass spectrometry combined with isotopic labeling experiments and theoretical computations was applied to investigate the fragmentation reaction mechanisms of two kinds of N-aryl lactam compounds. The main contents are as follows:1. The fragmentation mechanisms of protonated bicyclic caprolactamsThe fragmentation of protonated bicyclic caprolactams gave rise to product ions a and b by neutral loss cinnamaldehyde derivatives and2-oxo-N-phenylbutanamide derivatives, respectively, in high-energy collision-induced dissociations mass spectrometry. According to studying a series of compounds with different substitutents at phenyl ring, it wasdemonstrated that electron-donating groups at phenyl ring were in favor of neutral loss 2-oxo-N-phenylbutanamide derivatives, whereas electron-withdrawing groups at phenyl ring were in favor of neutral loss cinnamaldehyde derivatives. Density functional theory calculations indicated that the oxygen atom of lactam part is the thermodynamically most favorable site and the additional proton should migrate from this initially protonated site to the dissociative protonation site before charge induced heterolytic cleavage. The rate of the fragmentation reaction is controlled by thermodynamics factors. Moreover, the kinetic method proposed that the fragmentation reaction proceeds via a proton-bound complex of 2-oxo-N-phenylbutanamide/cinnamaldehyde intermediate.2. The fragmentation mechanisms of protonated 4-substituted isoquinolinonesCollision-induced dissociations of protonated 4-substituted isoquinolinones were investigated by electrospray ionization tandem mass spectrometry and two major competitive routes were observed. In one channel, neutral loss benzene derivatives resulted in product ion a. In another channel, neutral elimination of 2-(phenylamino)-1H-inden-1-one derivatives led to fragmentation ion b. Density functional theory calculations demonstrated that the amide oxygen is the thermodynamically most favorable site and heterolytic cleavages are triggered by the proton migrating from the initially protonated site to the dissociative protonation sites. The rate of the fragmentation reaction is controlled by thermodynamics factors. The natural logarithm of the intensity ratios of ion a and ion b is related linearly with the Hammett substitutent constants,which demonstrated that electron-donating groups at phenyl ring were in favor of neutral loss benzene derivatives, whereas electron-withdrawinggroups at phenyl ring were in favor of neutral loss2-(phenylamino)-1H-inden-1-one derivatives.