Synthesis and multimodal characterization of flavonols: electrochemical, spectroscopic, and DFT approaches

Five flavonols bearing electron-donating and electron-withdrawing substituents were synthesized and characterized by NMR spectroscopy, mass spectrometry, UV-Vis spectroscopy, and cyclic voltammetry. Density functional theory (DFT) and time-dependent DFT (TDDFT) calculations were performed to investigate their molecular geometries, frontier molecular orbitals, electronic structures, and excited-state properties. The optimized geometries revealed that flavonols containing substituents at both the C2' and C6' positions adopt non-planar conformations, whereas the remaining derivatives are essentially planar. Potential energy surface calculations showed that steric interactions between the 3-hydroxyl group and the ortho substituents stabilize the twisted conformations and reduce π-conjugation. The HOMOs were predominantly localized on rings B and C, while the LUMOs were distributed over rings A and C, indicating similar oxidation and reduction centres throughout the series. Electron-donating substituents raised the HOMO energies, resulting in lower oxidation potentials and red-shifted UV-Vis absorption bands. TDDFT calculations accurately reproduced the experimental absorption spectra and confirmed that the lowest-energy electronic excitation is dominated by the HOMO→LUMO transition. Strong correlations were observed between the experimental electrochemical energy gap and the DFT-calculated HOMO-LUMO energy gap (R² = 0.92), while excellent agreement was obtained between the calculated and experimental absorption maxima (R² = 0.98). The excellent agreement between experimental and computational parameters establishes quantitative structure-electronic property relationships for flavonols by integrating DFT, TDDFT, UV-Vis spectroscopy and electrochemistry, and provides a predictive basis for the rational design of flavonol-based functional materials and biologically active derivatives.