Protonated N-benzyl- and N-(1-phenylethyl)tyrosine amides dissociate via ion/neutral complexes

The collisional-induced dissociations (CID) of the [M+H]⁺ ions of molecules having benzyl groups attached to N-atoms have been proposed to involve migration of the benzyl group through the intermediacy of ion/neutral complexes (INCs). We report the investigation of the mechanism of dissociation of protonated N-benzyl- and N-(1-phenylethyl)tyrosine amides by electrospray ionization (ESI) tandem mass spectrometry (MS/MS) and density functional theory (DFT) calculations.

The amides were synthesized from the corresponding amino acids and amines. The ESI-MS/MS spectra were recorded using an Agilent QTOF 6540 mass spectrometer. The DFT calculations were performed by using Gaussian 09 software. The structures of the [M+H]⁺ ions, intermediates, products and transition states (TS) were optimized at the B3LYP/6-31G(d,p) level of theory.

CID of the [M+H]⁺ ions of N-benzyltyrosine amide yields two product ions due to rearrangements: (i) the [M+H-74]⁺ ion (m/z 197) due to benzyl migration to the hydroxyphenyl ring and (ii) the [M+H-45]⁺ ion (m/z 226) due to benzyl migration to the NH₂ group. DFT calculations suggest that the rearrangements occur through an INC in which the benzyl cation is the cation partner. The [M+H]⁺ ion of N-(1-phenylethyl)tyrosine amide rearranges to an INC of the 1-phenylethyl cation. Subsequent elimination of styrene occurs by transfer of a proton from the 1-phenylethyl cation to the neutral partner.

The [M+H]⁺ ions of both N-benzyl (1) and N-(1-phenylethyl) (2) tyrosine amide rearrange into INCs. The dissociation of [M+H]⁺ ion of 1 yields the benzyl cation and [M+H-74]⁺ and [M+H-45]⁺ due to benzyl migration to the hydroxyphenyl ring and NH₂ group, respectively. However, the formation of the [M+H-74]⁺ ion is not observed when the aromatic ring is deactivated. The [M+H]⁺ ion of 2 either dissociates to form the 1-phenylethyl cation or [M+H-styrene]⁺ . Copyright © 2015 John Wiley & Sons, Ltd.