Fluorescence-Based Investigations of Alcohol Co-Solvents on the Nature of Cyclodextrin Inclusion Complexation

Abstract

The effects of aliphatic alcohol co-solvents on the nature of inclusion complexes formed between 2-anilinonaphthalene-6-sulfonic acid (2,6-ANS) and β- or γ-cyclodextrin were studied with the use of steady-state and time-resolved fluorescence spectroscopy. Complementary information about the effects of alcohol on cyclodextrin (CD) inclusion complexation has been obtained. The fluorescence lifetimes are recovered from multifrequency phase and modulation experiments in concert with a global analysis scheme. In all cases, the best fitting model contained two decay times. One of the components of the intensity decay is short lived and discrete and the other is a longer-lived distributed component. Evidence from the emission peak intensity, the center and width of the lifetime distribution, and the molar fraction of lifetime components indicates that alcohol modifiers have two distinct effects on the cyclodextrin inclusion complex. First, alcohol co-solvents can disrupt the 2,6-ANS-CD complex through competitive binding with the CD cavity, and to a lesser extent they increase the bulk solvent hydrophobicity. Second, alcohols can enhance the stability of certain 2,6-ANS inclusion complexes by formation of higher-order complexes (2,6-ANS-CD-ROH n). These two effects are governed by the cavity size and the structure and concentration of the alcohol co-solvents. These observations are consistent with the roles of the van der Waals interactions, the hydrophobic effect, and the stearic effects as important factors in CD inclusion complexation. Finally, the average rotational correlation time, recovered from steady-state anisotropy experiments, indicates that the rotational dynamics of the 2,6-ANS-CD complex are regulated by the size and concentration of the alcohol co-solvent.