Fragmentation of Protonated 2-(2-Phenylethyl)Chromones from Agarwood: The Diagnostic Role of Ion/Neutral Complexes as Reactive Intermediates

Abstract

A positive-ion electrospray ionisation collision-induced dissociation mass spectrometric study on the fragmentation of the [M + H](+) ions of 2-(2-phenylethyl)chromone and a set of nine hydroxyl- and/or methoxy-substituted derivatives has revealed a highly prominent fragmentation channel, the loss of benzoquinomethanes or a benzaldehyde, respectively, as a diagnostic feature for 2-(2-phenylethyl)chromones that bear a hydroxyl group at the para- (4'-), ortho- (2'-) and/or benzylic (α-) position of the phenylethyl residue. Derivatives that bear only a meta- (3'-) hydroxyl group do not undergo this elimination. The intermediacy of ion/neutral complexes (INCs) is invoked to explain this fragmentation, which involves the remarkable intra-complex proton or hydrogen atom transfer from the remote 4'-OH (or the 2'- or α-OH) functionalities. Density functional theory (B3LYP/6-31G(d)) calculations confirm the energetic preference for these elimination channels and agree with the limited thermochemical data known for para- and ortho- benzoquinomethanes. The INC-mediated losses of the benzaldehydes from the [M + H](+) ions of the α-hydroxy-substituted 2-(2-phenylethyl)chromones correspond to a particularly facile (vinylogous) Grob fragmentation. The study may be viewed as a telling example of the diagnostic role of ion/neutral complexes as intermediates for the structural assignment of constitutional isomers by mass spectrometry.

Free radical‐initiated peptide sequencing (FRIPS)‐based cross‐linkers for improved peptide and protein structure analysis

“…A specific and diagnostic fragmentation reaction was found during FRIPS of Tyr‐containing peptides, taht is, the loss of C 7 H 6 O (4‐methylenecyclohexa‐2,5‐dienone) with a characteristic mass of 106 u, as rationalized in Figure and discussed by Hopkinson and Siu . Interestingly, the same neutral loss was found in the fragmentation of protonated (2‐phenylethyl)chromones as reported by Kuck et al…”

Comparing the fragmentation reactions of protonated cyclic indolyl α‐amino esters in quadrupole/orbitrap and quadrupole time‐of‐flight mass spectrometers

“…As reactive intermediates in gas‐phase ionic reactions, ion‐neutral complexes (INCs) are applied to species in which an ion and a neutral are held together mainly by electrostatic attraction. Unimolecular decomposition processes mediated by INCs involve either a direct separation without a significant barrier or further internal ion‐molecule reactions . Obviously, the kinetic and mechanistic role of INCs hinges heavily on their lifetime behaviors .…”

Ortho‐hydroxyl effect and proton transfer via ion–neutral complex: the fragmentation study of protonated imine resveratrol analogues in mass spectrometry

“…Benzyl cations are highly reactive intermediates in various chemical and biochemical reactions and usually short‐lived in solution . In an INC, benzyl cations formed during the CID process may lead to hydride transfer, electron transfer, proton transfer, electrophilic aromatic substitution and nucleophilic aromatic substitution …”

“…[35][36][37][38][39][40] In an INC, benzyl cations formed during the CID process may lead to hydride transfer, electron transfer, proton transfer, electrophilic aromatic substitution and nucleophilic aromatic substitution. [7,8,11,20,[35][36][37][38][39][40][41][42][43][44][45][46][47][48][49] In the previous studies, the proton donation ability of the 4-methylbenzyl cation was found to be dramatically enhanced by its methylene arenium character. [20,39] In contrast, the positive charge cannot reside at meta-position of the 3-methylbenzyl cation; therefore, the meta-methyl group cannot react as a proton donor.…”

“…[20,39] In contrast, the positive charge cannot reside at meta-position of the 3-methylbenzyl cation; therefore, the meta-methyl group cannot react as a proton donor. [39] A recent paper also reported and discussed intracomplex hydrogen transfer processes that gave rise to the elimination of para-and ortho-quinomethane neutrals, CH 2 = C 6 H 4 = O, from the precursor [M + H] + ions of 2-(2-phenylethyl)chromones obtained from agarwood components.. [49] Although 4-methylbenzyl cation has been determined as a proton donor in several occasions, seldom have the acidity potential of ortho-, meta-or para-hydroxylbenzyl cations been reported.…”