Unusual negative charge‐directed fragmentation: collision‐induced dissociation of cyclopentenone oxylipins in negative ion mode

RATIONALE Oxidized fatty acids, and particularly cyclopentenone oxylipins, are electrophilic metabolites that play diverse physiological roles. Current understanding is limited regarding how ion fragmentation provides essential information about oxylipin structures. In this work, unusual products of the collisional activation of deprotonated cyclopentenone oxylipins were investigated. METHODS The cyclopentenone oxylipin 12-oxo-phytodienoic acid (OPDA) and its 18O-labeled forms were ionized using negative-ion mode electrospray ionization, and product ion tandem mass (MS/MS) spectra were generated using collision-induced dissociation (CID). CID-MS/MS spectra were also generated for several cyclopentenone prostaglandins. RESULTS Upon collisional activation, deprotonated cyclopentenone oxylipins 12-oxo-phytodienoic acid (OPDA) and dinorOPDA form a characteristic and dominant product ion at m/z 165 that is attributed to charge-directed hydride migration to the electrophilic enone ring followed by elimination of neutral C7H10O2 from the carboxyl end. In contrast, pseudo-MS3 spectra of deprotonated cyclopentenone prostaglandins exhibited a different fragmentation behavior, in that cleavage near C = C bonds is directed by the carbonyl group in the nearby cyclopentenone ring. CONCLUSIONS Two different routes of fragmentation are proposed for cyclopentenone fatty acids with saturated and unsaturated side chains. We predict that this behavior may facilitate the identification of novel cyclopentenone oxylipins and accelerate discoveries of their biological regulatory functions. Copyright © 2014 John Wiley & Sons, Ltd.