Low-energy collision-induced dissociation tandem mass spectrometry of 7-acetonyloxycoumarins

Coumarins are naturally occurring, oxygen-containing heterocycles with considerable pharmaceutical potential. For structural elucidation of natural or synthetic coumarins, tandem mass spectrometry (MS(n)) represents an essential tool. In this study, fragmentation characteristics of twenty-two 7-acetonyloxycoumarins, having promising anti-inflammatory properties, were investigated with low-energy collision-induced dissociation (CID).

Accurate mass measurements were performed on a 12-T Fourier transform ion cyclotron resonance (FT-ICR) instrument. Most CID-MS(n) measurements were performed on a quadrupole ion trap (QIT) instrument, except some additional CID-MS(2) measurements performed on the FT-ICR instrument for further confirmation of some fragment ions. Positive-ion electrospray ionization (ESI) was employed throughout. Density functional theory (DFT) calculations (B3LYP) were carried out to analyze putative ion structures/fragmentation channels.

The most favourable dissociation channel for [M + H](+) ions of 7-acetonyloxycoumarins was the elimination of a C3H5O(●) radical (57 Da) from the 7-acetonyloxy group via homolytic bond cleavage. The resulting phenolic radical ion was the primary fragment ion for the most compounds studied. Losses of even-electron neutrals, C3H4O and C3H6O (56 and 58 Da), were also observed. These primary eliminations were accompanied with other characteristic neutral losses from the coumarin skeleton, including H2O, CO, CO2, and C2H2O (ketene). In addition, propene (C3H6) loss was also observed for 4-propyl or 3-ethyl-4-methyl-substituted compounds.

The studied coumarins showed interesting characteristics in low-energy CID due to the presence of a 7-acetonyloxy group, leading to both even- and odd-electron product ions. The main dissociation channels observed for each compound were highly dependent on the substituents in the benzopyranone ring. The present results will advance our knowledge on the dissociation characteristics of both synthetic and natural coumarins.