Charge-Dependent Modulation of S–H vs O–H Excited-State Intramolecular Proton Transfer

Abstract

Substituent effects critically influence electronic coupling and proton-transfer dynamics in excited-state intramolecular proton transfer (ESIPT), yet a quantitative link between charge redistribution and ESIPT behavior remains elusive. Here, we employ Natural Population Analysis (NPA) and the charge of the Substituent Active Region (cSAR) to quantify electronic responses for hydroxyl- versus thiol-functionalized flavonoids in ESIPT, enabling direct comparison with experimentally derived spectroscopic observations. Two distinct charge-redistribution regimes emerge: e: opposed shifts, in which donor and acceptor sites respond inversely to substitution, and concerted shifts, in which both sites gain charge in parallel. Thiol derivatives exhibit stronger substituent sensitivity and enhanced electronic polarization, whereas hydroxyl analogues display more limited yet directionally consistent charge responses across both donor and acceptor sites. Experimentally, this contrast results in a broader tunability of ESIPT rates in thiol systems, while hydroxyl analogues with similar substitution patterns show a narrower kinetic variation. Importantly, the excited-state donor and acceptor charges correlate far more strongly with cSAR(R’’) than with classical Hammett σ_p parameters, underscoring the superior predictive power of cSAR in systems where conventional descriptors fail. Time-resolved fluorescence experiments corroborate the theoretical predictions, revealing a direct correlation between charge redistribution and ESIPT rate. These findings establish the charge-based descriptors as predictive, mechanistic tools for understanding and designing ESIPT-active chromophores.