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.