The Mechanism of a Retro-Diels–Alder Fragmentation of Luteolin: Theoretical Studies Supported by Electrospray Ionization Tandem Mass Spectrometry Results

Abstract

The mechanisms of retro-Diels–Alder fragmentation of luteolin are studied theoretically using the Density Functional Theory method (B3LYP hybrid functional) together with the 6-311++G(d,p) basis set and supported by electrospray ionization tandem mass spectrometry (ESI-MS) results. The reaction paths leading to the formation of 1,3A− and 1,3B− fragment ions observed as the main spectral features in the ESI-MS spectrum are described and discussed, including the structures of the transition states and intermediate products. The heights of the activation energy barriers which have to be overcome along the reaction paths corresponding to 1,3-retrocyclization cleavage of the ionized luteolin are predicted to span the 69–94 kcal/mol range (depending on the initial isomeric structure) for the concerted retrocyclization mechanism and the 60–89 kcal/mol (first barrier) and 24–52 kcal/mol (second barrier) barriers for the stepwise mechanism (also depending on the initial isomeric structure). It is also demonstrated that the final fragmentation products (1,3A− and 1,3B−) are in fact represented by various isomeric systems which are not experimentally distinguishable. In addition, the absence of the spectral feature corresponding to the [M-B]− fragment ion formed by the rupture of the C-C bond connecting luteolin’s B and C rings (which does not occur during the ESI-MS experiment) is explained by much larger energy barriers predicted for such a process.