Mechanistic Insights into the Combined Effects of Substituent Modification, Electronegativity Modulation, Solvent Polarity, and External Electric Fields on ESIPT and Antioxidant Potential in 4′,5-Dihydroxy-7-methoxyflavone

Density functional theory (DFT) and time-dependent density functional theory (TD-DFT) calculations were employed to systematically investigate the effects of substituent electronic characteristics, para-position heteroatom substitution, solvent polarity, and external electric fields (EEFs) on excited-state intramolecular proton transfer (ESIPT), emission photophysics, and antioxidant-related reactivity of 4′,5-dihydroxy-7-methoxyflavone (GKO) and its derivatives. Geometric, infrared vibrational, reduced density gradient (RDG), frontier molecular orbital (FMO), natural bond orbital (NBO), and potential energy curve (PEC) analyses reveal pronounced photoinduced reorganization of the intramolecular hydrogen-bonding environment. For GKO in dichloromethane (DCM), the H···O distance decreases from 1.670 Å in S0 to 0.987 Å in S1, accompanied by substantial elongation of the donor O–H bond, indicating pronounced proton displacement toward the acceptor upon excitation. The ground state proton transfer barrier of GKO is 6.41 kcal mol–1, decreasing to 4.57 kcal mol–1 with −CN substitution and increasing to 7.32 kcal mol–1 with −NH2 substitution. O → S substitution at the para position of the proton acceptor lowers the S0 barrier to 5.26 kcal mol–1, whereas increasing solvent polarity from DCM to DMSO produces only a minor decrease to 6.31 kcal mol–1. In the excited state, no apparent energy maximum is observed along the selected O–H proton transfer coordinate for any investigated system. Unconstrained S1 optimizations instead yield spontaneous proton migration without convergence to a stable normal excited-state (E*) minimum. The energy decrease toward the proton transferred region increases from 10.84 kcal mol–1 for GKO to 14.61 kcal mol–1 for GKO-NH2, demonstrating substantial substituent-dependent modulation of the S1 potential energy profile. EEFs induce pronounced nonlinear and direction-dependent changes in proton transfer energetics. A positive field of +0.01 au causes only minor perturbation of the S1 profile, whereas +0.02 au introduces finite barriers of 2.10 and 2.80 kcal mol–1 in DCM and DMSO, respectively. Negative fields produce substantially larger S1 barriers, reaching 10.07 kcal mol–1 in DCM and 11.79 kcal mol–1 in DMSO. Photophysical calculations show that all systems exhibit characteristic K* emission with Stokes shifts exceeding 110 nm, consistent with substantial excited-state structural relaxation associated with ESIPT. For GKO in DCM, the calculated keto emission is 482.67 nm with a Stokes shift of 148.89 nm. −CN substitution shifts the emission to 446.77 nm and increases the oscillator strength from 0.2719 to 0.4849, whereas −NH2 produces a pronounced red shift to 770.51 nm, a Stokes shift of 399.27 nm, and a reduced oscillator strength of 0.0169. EEFs further regulate emissive-state characteristics: +0.01 au increases the K* oscillator strength to 0.5691, while +0.02 au induces competition between E* and K* emission and changes the dominant emissive state. Negative fields strongly suppress the E* transition, yielding nearly zero oscillator strengths. Antioxidant-related calculations distinguish the roles of electron and hydrogen transfer descriptors. Photoexcitation decreases the IP of GKO from 7.52 to 6.71 eV, indicating enhanced electron transfer propensity, while −NH2 substitution lowers the O–H BDE from 97.662 to 78.960 kcal mol–1, favoring hydrogen atom transfer. Overall, substituent characteristics, para-position heteroatom substitution, solvent polarity, and EEFs exert distinct and state-dependent effects on ESIPT energetics, emission photophysics, and electron and hydrogen transfer-related reactivity, providing quantitative insights into the regulation of ESIPT and a theoretical basis for designing molecular systems with tunable optical and antioxidant-related properties.