Geometrical isomerization of hydroxycinnamic acid under UV-light: Structural plasticity as a driver of metabolite...

Hydroxycinnamic acid (HCA)-containing molecules such as chlorogenic acids undergo trans/cis isomerization under UV light, a process expected to intensify with increasing sunlight exposure under climate change. Advanced analytical and data visualization methods to capture such dynamic transformations in nutraceutical compounds are urgently required. To investigate this transformation, methanolic extracts of a hemi-parasitic plant Viscum combreticola were exposed to UV light and profiled using ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC-qTOF-MS). Multivariate analysis (PCA and biplots) revealed that UV-sensitive metabolites predominantly contained HCA moieties, with clearer separation between treated and untreated samples emerging at longer chromatographic run times. Molecular networking was also used to show that robust chromatographic separation is critical in isomer differentiation and visualizing metabolomic changes in samples. Findings of this study demonstrate that UV irradiation enhances metabolite diversity by driving HCA photoisomerization. DFT modeling of selected cinnamic acid-containing molecules showed that successful isomerization depends on the co-localization of the HOMO and LUMO within the same structural moiety, particularly around the olefinic functional group of the cinnamic acid unit. Most importantly, this study demonstrates that HCAs are versatile molecules that exhibit structural plasticity under UV light by producing cis isomers whose biological consequences remain unexplored.