Microenvironmental Modulation of Bromocresol Green upon γ-Cyclodextrin Association Characterized by UV-Vis Spectral Trajectory Analysis.

Cyclodextrins (CyDs) provide a microenvironment distinct from the bulk solvent by incorporating guest molecules within their hydrophobic cavities; thus, they can induce changes in the physicochemical properties of drugs. In this study, we investigated how γ-CyD association alters the microenvironment experienced by a guest molecule, taking bromocresol green (BCG) as a model reporter molecule. BCG was selected because its ultraviolet-visible (UV-Vis) spectrum sensitively reflects acid-base equilibrium and local solvation-related changes. The results indicated that, upon γ-CyD addition, the spectral contribution assigned to the dianionic form of BCG increased. In addition, a bathochromic shift was observed for the absorption band assigned to the dianionic form. By applying singular value decomposition (SVD) to the UV-Vis spectra, spectral variations associated with acid-base equilibrium and bathochromic shifts were empirically resolved as dominant components. Through trajectory analysis of these components, the γ-CyD-induced microenvironmental effect on BCG was expressed in terms of reference scales based on pH-dependent and dimethyl sulfoxide (DMSO)/water-dependent spectral changes. Based on this trajectory analysis, the γ-CyD-induced spectral changes of BCG were operationally expressed as corresponding to an apparent acid-base equilibrium state comparable to that of an aqueous solution at pH 5.66 and to a bathochromic response observed in a 50.8% DMSO/water mixed solvent. These results indicate that γ-CyD association alters the apparent microenvironment experienced by BCG and that SVD-based trajectory analysis enables this effect to be described in terms of physically interpretable spectral reference coordinates.