The bimolecular gas-phase reaction of protonated alkyldipeptides with acetonylacetone

The gas-phase reaction of protonated alkyldipeptides with acetonylacetone has been studied in a Fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometer. The reaction is identified as the gas-phase analogue of Paal-Knorr pyrrole synthesis. Under thermal conditions, the reaction complex loses a water molecule during a condensation reaction, which couples the dipeptide to the acetonylacetone molecule via an imine bond. Low energy collisional activation of the long-lived imine product ion induces additional loss of a water molecule to form the protonated 2,5-dimethylpyrrole derivative of the dipeptide. Detailed insight into the mechanism is obtained by a comparison of the reactivity of various alkyldipeptides with model compounds with amino functional groups. The reaction is catalysed by the peptide carbonyl groups, which assist in the protonation of the acetonylacetone carbonyl oxygen atoms, making the acetonylacetone carbonyl carbon atoms susceptible to nucleophilic attack by the peptide amino group. From both the previously studied bimolecular hydrogen-deuterium exchange behaviour and the presently studied reaction with acetonylacetone, it follows that the bimolecular reactivity of protonated alkyldipeptides is related to the extent of mobility of the proton within the reactive complex.