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.

Rationalising the retro‐Diels‐Alder fragmentation pattern of viscutins using electrospray interface‐tandem mass spectrometry coupled to theoretical modelling

“…Therefore, understanding these mechanisms at a molecular level using theoretical modelling may provide an insight into the stepwise reactions that result in RDA fragmentation products. Śliwka‐Kaszyńska et al 11 studied the fragmentation pattern of luteolin employing theoretical modelling accompanied by electrospray interface‐mass spectrometry (ESI‐MS) data. However, employing several tools to rationalise the RDA fragmentation patterns might be beneficial in identifying the most accurate fragmentation pathway of a given compound.…”

“…Therefore, understanding these mechanisms at a molecular level using theoretical modelling may provide an insight into the stepwise reactions that result in RDA fragmentation products. Śliwka-Kaszy nska et al 11…”

“…Due to various reported health benefits of other commonly studied flavonoids, mainly attributed to their antioxidant and metal chelating abilities, 10 sensitive and effective methods should be employed for their characterisation and identification. The MS/MS fragmentation patterns of various flavonoid subclasses, including flavones, flavonols, flavanones, isoflavones, isoflavanones and chalcones, 7,11,12 have been studied extensively based on their unique fragmentation patterns through the retro-Diels-Alder (RDA) cleavage of the flavonoid scaffold. However, similar studies on flavans such as viscutins are still limited, if there are any, at the moment.…”

Comprehensive profiling of chemical composition of Gleditsiae spina using ultra‐high‐performance liquid chromatography coupled with electrospray ionization quadrupole time‐of‐flight mass spectrometry

“…Therefore, it is essential to develop a rapid and effective analytical method for identifying the chemical components of GS systematically and comprehensively. Ultra‐high‐performance liquid chromatography–quadrupole time‐of‐flight–tandem mass spectrometry (UHPLC–QTOF–MS/MS) coupled with data mining strategy allows rapid identification of Chinese herbal medicine constituents and detection of potential new compounds 13–18 ; due to these advantages over traditional extraction and separation methods, the technology is widely utilized in the manifestation of TCM ingredients 19–24 …”

“…Ultra-high-performance liquid chromatography-quadrupole time-offlight-tandem mass spectrometry (UHPLC-QTOF-MS/MS) coupled with data mining strategy allows rapid identification of Chinese herbal medicine constituents and detection of potential new compounds [13][14][15][16][17][18] ; due to these advantages over traditional extraction and separation methods, the technology is widely utilized in the manifestation of TCM ingredients. [19][20][21][22][23][24] At present, only a few comprehensive profiles of GS chemical composition have been reported. 25 Besides, their identification mode mainly depended on the databases susceptible to imperfection accredited to nonuniform liquid-phase MS conditions and incompetency for identifying novel compounds.…”