Host−Guest Complexation of Neutral Red with Macrocyclic Host Molecules: Contrasting pKa Shifts and Binding Affinities for Cucurbit[7]uril and β-Cyclodextrin

Abstract

The photophysical properties of the phenazine-based dye neutral red were investigated in aqueous solution in the presence of the macrocyclic host molecule cucurbit[7]uril (CB7) using ground-state absorption as well as steady-state and time-resolved fluorescence measurements. The results are contrasted to those previously obtained for β-cyclodextrin (β-CD; Singh et al. J. Phys. Chem. A2004, 108, 1465). Both the neutral (NR) and cationic (NRH⁺) forms of the dye formed inclusion complexes with CB7, with the larger binding constant for the latter (K = 6.5 × 10³ M^-1 versus 6.0 × 10⁵ M^-1). This result differed from that for β-CD, where only the neutral form of the dye was reported to undergo sizable inclusion complex formation. From the difference in binding constants and the pK_a value of protonated neutral red in the absence of CB7 (6.8), an increased pK_a value of the dye when complexed by CB7 was projected (∼8.8). This shift differed again from the behavior of the dye with β-CD, where a decreased pK_a value (ca. 6.1) was reported. The photophysical properties of both NR and NRH⁺ forms showed significant changes in the presence of CB7. Fluorescence anisotropy studies indicated that the inclusion complexes of both forms of the dye rotate as a whole, giving rotational relaxation times much larger than that expected for the free dye in aqueous solution. The thermodynamic parameters for the NRH⁺·CB7 complex were investigated in temperature-dependent binding studies, suggesting an entropic driving force for complexation related to desolvation of the cation and the removal of high-energy water molecules from the CB7 cavity.