Density Functional Theory Analysis of Luteolin Molecular Structure and Spectrum

Luteolin is a natural flavonoid compound. Numerous studies have demonstrated that luteolin exhibits pharmacological activities such as antioxidant and antitumor effects; however, the molecular mechanisms linking its electronic structure to pharmacological activities have not been systematically elucidated. Structure determines properties, which are crucial factors for investigating the chemical characteristics and reaction mechanisms. This study aims to analyze its electronic structure parameters and reveal the correlation between active sites and biological functions by using density functional theory. The geometric configuration of luteolin was optimized by the B3LYP-D3-(BJ)/6-311G-(d,p) method. Frontier molecular orbitals (FMOs), electron affinity (EA), ionization energy (ionization potential (IP)), density of states (DOS), bond dissociation energy (BDE), proton affinity (PA), molecular surface electrostatic potential (MESP), and vibrational spectra were calculated. The chemical shifts of ¹H NMR and ¹³C NMR were predicted using the gauge-including atomic orbital theory. Results show that geometric optimization and spectral analysis confirm the presence of hydrogen bonds and conjugated systems in luteolin, indicating that its antioxidant and antitumor potential are closely associated with the electron delocalization capacity of the conjugated backbone and the stability modulation of intramolecular hydrogen bonds. DOS analysis reveals that the p-orbital-dominated conjugated system is the core of its chemical stability and antioxidant activity; functional groups such as carbonyl and hydroxyl groups participate in electronic state construction through p-orbital hybridization/conjugation, ultimately determining the molecular structure-function relationship. With a narrow HOMO-LUMO energy gap (4.37 eV), low BDE (304.27 kJ/mol), and low IP (724.44 kJ/mol), luteolin synergistically and efficiently scavenges free radicals via a hydrogen atom transfer-dominated mechanism, combined with sequential proton loss electron transfer (SPLET) and single electron transfer followed by proton transfer (SET-PT), suggesting potent antioxidant and antitumor capabilities. Based on the low BDE (304.27 kJ/mol) and the distribution of electrophilic/nucleophilic regions in MESP analysis, the phenolic hydroxyl group on ring B (O20-H30) and the carbonyl group on ring C (C3O11) are identified as potential key active sites for antioxidant and antitumor activities. This study investigates the structural characteristics, spectral properties, and key active sites of luteolin, providing a theoretical basis for its antioxidant and antitumor pharmacological effects and offering theoretical guidance for its targeted drug design.