Redox properties of quercetin iron Ii complex with enhanced antioxidant and antiviral activities

Quercetin is a naturally occurring flavonoid widely recognized for its potent antioxidant, anti-inflammatory, and anticancer effects. However, its clinical application is limited by low water solubility and poor bioavailability. In this study, the complexation of quercetin with iron (II) ions was systematically investigated through electrochemical, spectroscopic, biological, and computational techniques to improve its physicochemical and pharmacological performance. Cyclic voltammetry revealed that quercetin undergoes irreversible oxidation due to semiquinone and para-quinonemethide formation, while Fe(II) exhibited quasi-reversible redox behavior, which became less reversible upon complexation, suggesting altered electron transfer kinetics. The stability constant (log βMX = 3.29) and the negative Gibbs free energy (ΔG = - 19.07 kJ/mol) confirmed spontaneous and thermodynamically favorable complex formation. UV-Vis spectroscopy showed significant bathochromic shifts (Δλ = 66 nm), and the continuous variation method established a 1:1 metal-to-ligand stoichiometry. ¹H NMR spectroscopy and X-ray diffraction patterns further confirmed the coordination sites and structural modifications upon metal binding. The Fe(II)-quercetin complex demonstrated superior antioxidant capacity in DPPH radical scavenging assays, with an IC₅₀ of 21.86 µg/mL compared to 23.47 µg/mL for free quercetin, confirming enhanced radical scavenging activity upon complexation. Cytotoxicity assays on HepG2 and MCF-7 cancer cell lines revealed enhanced bioactivity of the complex, with IC₅₀ values of 26.80 and 18.60 µM, respectively. Antifungal testing showed moderate inhibition against Candida albicans. Molecular docking simulations using the SARS-CoV-2 spike protein (PDB: 7JWY) indicated stronger binding affinity for the complex (- 5.42 kcal/mol) than quercetin alone, suggesting potential antiviral efficacy. Additionally, DFT calculations revealed increased softness and electrophilicity of the complex, supporting its enhanced reactivity. Collectively, these findings position the Fe(II)-quercetin complex as a promising multifunctional agent with potential applications in antioxidant therapy, cancer treatment, and antiviral drug development.