Effect of Photoacid Strength on Fluorescence Modulation of 2-Naphthol Derivatives inside β-Cyclodextrin Cavity: Insights from Fluorescence, Isothermal Calorimetry, and Molecular Dynamics Simulations.

Abstract

Fluorescence response of a photoacid inside a confined environment often differs markedly from the bulk response. Is there any correlation between the extent of fluorescence modulation and the strength of the photoacid? Here, we used three photoacids: 2-naphthol (2OH, pKa* = 3.3), 6-sulfonate-2-naphthol (6SO3-2OH, pKa* = 3.06), and 6-cyano-2-naphthol (6CN-2OH, pKa* = 0.6) with remarkably different excited-state acidities to investigate fluorescence modulation inside the nanocavity of β-cyclodextrin (β-CD). Interestingly, we found strong fluorescence modulation for 2OH and 6SO3-2OH but almost none for 6CN-2OH. Isothermal calorimetry measurements showed that all three fluorophores form 1:1 inclusion complex with comparable binding constants (285, 420, and 580 M-1 for 2OH, 6SO3-2OH, and 6CN-2OH, respectively). Molecular dynamics simulation further revealed that binding modes are quite similar, and the distribution of water molecules around the proton-donating hydroxyl group of the photoacids are also comparable. Consequently, the difference in the fluorescence response should be accounted solely to the difference in the photoacidity strengths.