Sodium Adduct Formation of a UV-induced 4-cis-caffeoylquinic Acid Dimer: Insights from the UHPLC-qTOF-MS and DFT Modelling

Abstract Purpose Excessive sunlight exposure causes cinnamic acid-containing molecules in plants to undergo geometrical isomerization, increasing metabolomic diversity which poses an analytical challenge since the resulting compounds cannot be confidently distinguished by conventional mass spectrometry. However, past studies have demonstrated that the newly formed isomers can be distinguished from their trans counterparts through the formation of alkali metal adducts. Methods Herein, ultra high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-q-TOF-MS) was employed for the first time to characterize a sodium adduct of dimeric 4- cis -caffeoylquinic acid (4- cis -CQA) in UV-irradiated Viscum combreticola methanolic extracts which was observed at m/z 729.164. Density functional theory was used to rationalize the formation of this dimer. Results Theoretical modelling revealed that this compound was formed by various interactions between a neutral 4- cis -CQA and doubly deprotonated 4- cis -CQA molecules, with a Na + ion sandwiched between the two 4-CQA units through their functional groups. These interactions occurred through the π-system of the aromatic rings, along with multiple interactions, including the lone pairs of electrons on the oxygen atom of the keto group. Conclusion Findings of the current study further reaffirm that cis isomers of hydroxycinnamate containing molecules formed by UV irradiation bind sodium more efficiently than their trans counterparts, a phenomenon that we believe can be further exploited in the discovery and development of drugs based on metal binding as a therapeutic mechanism of action.