Binding of Cyclodextrins to Alicyclic and Aromatic Substrates: Complex Formation of α-, β-, and γ-Cyclodextrins with Substituted Cyclohexanecarboxylic Acids and Phenylalkanoic Acids

Complex binding constants of the three native cyclodextrins with seven cyclohexane derivatives (all possessing the carboxylic acid group) and with the series C6H5(CH2)nCOOH (n = 0 to 4) were measured in aqueous solution at 25 degrees C by potentiometry and the solubility method. These results, combined with literature data, indicate that alpha- and gamma-cyclodextrins bind with comparable strength to both the cyclohexyl and phenyl moieties, with beta-cyclodextrin binding significantly more strongly. These acid series are compared with several series CH3(CH2)nX, where X is CH3, COOH, COO-, OH, SO3-, etc., and it is concluded that the X group (for X other than methyl) contributes appreciably to complex stability, perhaps by means of an extracavity interaction. The COOH group provides a further augmentation of complex stability. NMR CIS and ROESY results indicate the presence of isomeric complexes in both the cyclohexyl and phenylalkanoic series, and clearly demonstrate the existence of intracavity inclusion. An NOE study of the alpha-cyclodextrin: cyclohexanecarboxylate system provides evidence for inclusion combined with interaction outside (that is, at the rim of) the cavity.