Ground-state pK_a and physicochemical characterization of resveratrone as a pH-responsive organic fluorophore

Elucidating acid dissociation constants (pK_a) is essential for organic molecules, particularly for tentative drug candidates and biocompatible fluorescent probes, as pK_a values determine the predominant ionic species and fluorescence properties in physiological environments. Consequently, accurate pK_a determination is critical for designing new drug candidates and biosensors. In this study, we determined the ground-state pK_a values of resveratrone, a photoproduct characterized by high fluorescence quantum yield, biocompatibility, and photodynamic therapy capability. To determine these unknown pK_a values, we employed a dual approach combining experimental and computational methods. pH-dependent spectroscopy data acquired over a pH range of 5.87-12.05 were analyzed by singular value decomposition, which simultaneously deconvolutes all contributing spectral species and correctly accounts for the overlapping deprotonation equilibria inherent to a diprotic system. This approach yielded macroscopic pK_a values of 7.81 (pK_a1) and 10.97 (pK_a2). These experimental values were validated through density functional theory calculations employing quantitative structure-property relationships and benchmarked against structurally analogous compounds. Notably, the proximity of pK_a1 to physiological pH establishes resveratrone as an ideal candidate for pH-responsive applications, as it undergoes ionization state transitions accompanied by distinct spectral changes in cellular environments. The determined pK_a values establish fundamental physicochemical properties that enable rational design of resveratrone-based fluorescent probes for pH sensing and pH-responsive drug delivery systems. This work provides an essential foundation for translating resveratrone from a photophysical entity into a functional biomedical tool.