Gas-phase fragmentation reactions of protonated benzofuran- and dihydrobenzofuran-type neolignans investigated by accurate-mass electrospray ionization tandem mass spectrometry.

We have investigated gas-phase fragmentation reactions of protonated benzofuran neolignans (BNs) and dihydrobenzofuran neolignans (DBNs) by accurate-mass electrospray ionization tandem and multiple-stage (MS ) mass spectrometry combined with thermochemical data estimated by Computational Chemistry. Most of the protonated compounds fragment into product ions B ([M + H-MeOH] ), C ([B-MeOH] ), D ([C-CO] ), and E ([D-CO] ) upon collision-induced dissociation (CID). However, we identified a series of diagnostic ions and associated them with specific structural features. In the case of compounds displaying an acetoxy group at C-4, product ion C produces diagnostic ions K ([C-C H O] ), L ([K-CO] ), and P ([L-CO] ). Formation of product ions H ([D-H O] ) and M ([H-CO] ) is associated with the hydroxyl group at C-3 and C-3', whereas product ions N ([D-MeOH] ) and O ([N-MeOH] ) indicate a methoxyl group at the same positions. Finally, product ions F ([A-C H O] ), Q ([A-C H O ] ), I ([A-C H O] ), and J ([I-MeOH] ) for DBNs and product ion G ([B-C H O] ) for BNs diagnose a saturated bond between C-7' and C-8'. We used these structure-fragmentation relationships in combination with deuterium exchange experiments, MS data, and Computational Chemistry to elucidate the gas-phase fragmentation pathways of these compounds. These results could help to elucidate DBN and BN metabolites in in vivo and in vitro studies on the basis of electrospray ionization ESI-CID-MS/MS data only.