Effects of functional groups on ESIPT and antioxidant activity of apigenin: A non-existent enol* state fluorescein

The development and enhancement of antioxidant drugs, which are aimed at mitigating DNA damage, mutations, and cancer, are of paramount significance in the biomedical sphere. In recent years, antioxidant drug molecules with photoluminescence have sprung up like mushrooms. Apigenin (AP), characterized by its distinctive property of excited state intramolecular proton transfer (ESIPT), plays a pivotal role in mediating antioxidant and anticancer activities. Despite being a representative molecule of the non-existent enol form (E*) state with ESIPT nature, there is a notable lack of theoretical investigations into its antioxidant properties. Herein, density functional theory (DFT) and time-dependent DFT methodologies were utilized to explore the effects of various functional groups on AP molecules in a methanol solvent. Studies have demonstrated that for the non-existent E* state fluorescence molecule AP, the ESIPT process can significantly enhance the antioxidant potency of AP and its derivatives. However, the introduction of electron-withdrawing groups significantly accelerated the ESIPT process while simultaneously suppressing the antioxidant activity of AP-CN. Conversely, the incorporation of electron-donating groups effectively inhibited the ESIPT process, yet markedly enhanced the antioxidant activity of AP-NH₂. This investigation furnishes vital perspectives and sources of reference for the conception and advancement of groundbreaking antioxidant medications that aim to tackle non-existent E* state molecules.