Complex formation between alpha-cyclodextrin and 4-substituted phenols studied by potentiometric and competitive spectrophotometric methods

Stability constants for complex formation between alpha-cyclodextrin and the conjugate acid and base forms of nine phenols were measured in aqueous solution at 25 degrees. The potentiometric method, in which the apparent acid dissociation constant of the phenol is measured as a function of cyclodextrin concentration, was supplemented by a modified version of a competitive spectrophotometric methyl orange method. For all phenols, the 1:1 stability constant for the conjugate base form (K11b) was larger than K11a for the conjugate acid form. Finite K12b values were found for phenols whose 4-substituents could tolerate a positive charge by electron delocalization. Complex stability, as measured by K11a and K11b, increases with electron density and polarizability at the 4-substituent. It is concluded that the 4-substituent is the sole or predominant site of binding for both the conjugate acid and base forms of the phenols. The general result that K11b is greater than K11a for any phenol is accounted for by relative delocalization of charge in the anion and neutral species.