To D or not to D? On estimating the microenvironment polarity of biomolecular cavities

Abstract

Knowledge of the local polarity of specific cavities in biopolymers can facilitate the design of selective low MW ligands that impact the structure and function of macromolecules. The most common tools for interrogating local polarity are fluorescent probes that are sensitive to their microenvironment. Researchers often evaluate and express this local polarity using dielectric constants, a parameter that reflects an inherent bulk property. A more appropriate expression should take into account solvent–solute interactions at the molecular level. Reevaluation of commonly used fluorophores illustrates the improved correlation between observed Stokes shift changes and E_T(30) values as compared to the corresponding dielectric constants.