The research uses Density Functional Theory to study the molecular and electronic behavior of new supramolecular dyads that link a flavonoid to C60 fullerene and allicin therapeutic agents. The research evaluates their dual functionality for photodynamic therapy and antioxidant pharmacology through electronic analysis of their operational mechanisms. The optimization of geometries shows that both dyads maintain stable molecular structures. The fullerene–flavonoid dyad achieves stability through powerful pi–pi stacking bonds, yet the allicin–flavonoid complex forms through hydrogen bonds and van der Waals forces, which produce substantial negative binding energies that prove thermodynamic stability. We used electronic structure parameters to study the charge transfer behavior of the system. The HOMO–LUMO energy gap of the fullerene–flavonoid dyad decreased substantially from the flavonoid alone, which indicates improved electronic polarizability and reduced photoexcitation energy needs for photosensitization applications. The molecular electrostatic potential maps on the flavonoid and fullerene cage were calculated to figure out how the photoinduced electron transfer from the flavonoid to the acceptor for reactive oxygen species production works. The allicin–flavonoid dyad shows a reduced HOMO–LUMO gap with orbital distribution across the entire complex, which indicates a cooperative effect that boosts electron donation for better radical scavenging.

The allicin–flavonoid complex exhibits a higher dipole moment than the fullerene-based dyad, which indicates better solubility in biological fluids with polar characteristics. The study shows that the allicin–flavonoid dyad acts as a strong synergistic antioxidant. Also, the fullerene– flavonoid structure can be a potential photosensitizer candidate according to quantum chemical descriptor analysis for drug development.

References

• Al-Salami, A., & Brown, K. (2024). Quantum chemical descriptors in rational drug design: Predicting bioavailability and reactivity. Journal of Pharmaceutical Sciences, 113(4), 855– 867. https://doi.org/10.1016/j.xphs.2023.12.001
• Clinical development of flavonoid-based drugs: A systematic review. (2023). Drug Discovery Today, 28(8), 103653. https://doi.org/10.1016/j.drudis.2023.103653
• Computational study on the therapeutic properties of allicin and its nanocomplexes: DFT and molecular docking approaches. (2025). Computational Biology and Chemistry, 110, 108045. https://doi.org/10.1016/j.compbiolchem.2024.108045
• Jan, A., Rehman, M. F., & Rahim, A. (2025). Integrating computational and experimental approaches in drug development: A case study of natural product derivatives. Journal of Molecular Structure, 1315, 139001. https://doi.org/10.1016/j.molstruc.2024.139001
• Ji, J., Ge, X., & Liu, Y. (2023). Synergistic antioxidant effects of natural compound dyads: A computational and experimental assessment. Bioorganic & Medicinal Chemistry, 82, 117237. https://doi.org/10.1016/j.bmc.2023.117237
• Kumar, P., & Srivastava, R. (2022). Molecular electrostatic potential (MEP) maps as a tool for predicting reactive sites and intra-molecular charge transfer. Journal of Computational Chemistry, 43(15), 1021–1033. https://doi.org/10.1002/jcc.26862
• Kwiatkowski, S., Knap, B., Przystupski, D., Saczko, J., Kędzierska, E., Knap-Czop, K., Kotlińska, J., Michel, O., Kotowski, K., & Kulbacka, J. (2018). Photodynamic therapy – mechanisms, photosensitizers and combinations. Biomedicine & Pharmacotherapy, 106, 1098–1107. https://doi.org/10.1016/j.biopha.2018.07.049
• Mendes, L. V., & Serrão, P. V. P. (2024). Benchmark of density functional theory for phenolic acids and flavonoids: A focus on antioxidant properties. Computational and Theoretical Chemistry, 1236, 114587. https://doi.org/10.1016/j.comptc.2024.114587
• Mroz, P., Tegos, G. P., Gali, H., Wharton, T., Sarna, T., & Hamblin, M. R. (2007). Photodynamic therapy with fullerenes. Photochemical & Photobiological Sciences, 6(11), 1139–1149. https://doi.org/10.1039/b711141j
• PDT and dietary antioxidants: Mechanisms of DNA protection and repair. (2025). Free Radical Biology and Medicine, 215, 1–15. https://doi.org/10.1016/j. freeradbiomed.2024.03.015
• Sampaio, R. G. V., Viana, J. O., & de Almeida, W. B. (2023). Electronic structure analysis of natural compounds with therapeutic potential using DFT: HOMO-LUMO, MEP, and Fukui function insights. Journal of Biomolecular Structure and Dynamics, 41(18), 8910– 8923. https://doi.org/10.1080/07391102.2022.2137240
• Schneider, H. J. (2021). Supramolecular chemistry in water. John Wiley & Sons.
• Silva, A. M., & Costa, F. G. (2024). A comparative DFT study on the reactivity and antiradical activity of allicin and its metabolites. Chemical Physics Letters, 837, 141054. https://doi.org/10.1016/j.cplett.2024.141054
• Spesia, M. B., & Durantini, E. N. (2014). Fullerenes and their derivatives as photosensitizers in photodynamic therapy. In Advances in Photodynamic Therapy: From Basic Science to Clinical Application (pp. 155–179). Academic Press.
• Zhang, P., Huang, H., & Chen, Y. (2019). C60-based nanocarriers for co-delivery of doxorubicin and photodynamic therapy. ACS Applied Materials & Interfaces, 11(12), 11421–11429. https://doi.org/10.1021/acsami.8b21686