Probing Flavonoid-Metal and Membrane Interactions by UV-Vis Spectroscopy: Structural Insights into Bioactivity and Bioavailability.

This study used UV-Vis absorption spectroscopy to investigate the interactions of flavonoids-baicalein (with ortho-dihydroxyl on the A-ring) and apigenin (with 4'-monohydroxyl on the B-ring)-with metal ions (Co2+, Ce4+) and membrane-mimetic systems (CTAB/SDS micelles, liposomes, vesicles). It revealed how flavonoid spectral properties related to molecular structure and microenvironment. Key findings were as follows: pH affected absorption spectra by altering phenolic hydroxyl protonation. Metal chelation depended on hydroxyl position: baicalein's A-ring ortho-dihydroxyl formed a stable charge-transfer complex with Cu2+. In acidic medium, apigenin reduced Ce(IV) more effectively than baicalein, which contradicted the classic antioxidant role of ortho-dihydroxyl groups. This showed that reaction microenvironments could change hydroxyl reactivity and electron transfer paths. Membrane-mimetic systems (liposomes/vesicles) raised apparent pKa, enhanced solubility and stability. The study first quantified distinct ΔpKa values for different flavonoids (e.g., quercetin vs. baicalein), which were linked to intramolecular H-bonding and membrane preference. Quercetin's B-ring ortho-dihydroxyl enabled the formation of hydrophobic interfacial anions in nanocarriers under alkaline pH, ensuring high stability. Kaempferol showed sustained leakage. These findings provided a basis for structure-guided flavonoid carrier design, bioavailability, and antioxidant delivery. By integrating reaction microenvironment, membrane interface effects, and carrier stability, this work clarified flavonoid bioactivity mechanisms and supported targeted delivery strategies.