Atypical cleavage of protonated N-fatty acyl amino acids derived from aspartic acid evidenced by sequential MS³ experiments

Lipidomics calls for information on detected lipids and conjugates whose structural elucidation by mass spectrometry requires to rationalization of their gas phase dissociations toward collision-induced dissociation (CID) processes. This study focused on activated dissociations of two lipoamino acid (LAA) systems composed of N-palmitoyl acyl coupled with aspartic and glutamic acid mono ethyl esters (as LAA(*D) and LAA(*E)). Although in MS/MS, their CID spectra show similar trends, e.g., release of water and ethanol, the [(LAA(*D/*E)+H)–C2H5OH]+ product ions dissociate via distinct pathways in sequential MS3 experiments. The formation of all the product ions is rationalized by charge-promoted cleavages often involving stepwise processes with ion isomerization into ion–dipole prior to dissociation. The latter explains the maleic anhydride or ketene neutral losses from N-palmitoyl acyl aspartate and glutamate anhydride fragment ions, respectively. Consequently, protonated palmitoyl acid amide is generated from LAA(*D), whereas LAA(*E) leads to the [*E+H–H2O]+ anhydride. The former releases ammonia to provide acylium, which gives the CnH(2n−1) and CnH(2n−3) carbenium series. This should offer structural information, e.g., to locate either unsaturation(s) or alkyl group branching present on the various fatty acyl moieties of lipo-aspartic acid in further studies based on MSn experiments.