Complexes of macrocycles with γ-cyclodextrin as deduced from NMR diffusion measurements

The complexes of 12-crown-4 (12C4), cyclen (12N4), and 1,4,7,10-tetrathiacyclododecane (12S4) with γ-cyclodextrin (γ-CD) were studied by NMR diffusion measurements in the absence and in the presence of inorganic and organic salts. The 12-crown-4:γ-CD system was also used to evaluate the effect of the nature of the cation and the anion on the association between the macrocycle and the γ-CD. In addition, we have studied the solvent effect and the pH effect on the association constant of the γ-CD:12C4 complex. Based on these measurements, the following conclusions could be reached: (1) All three macrocycles form complexes of moderate stability with γ-CD, (2) the association constants of these complexes are much higher in the absence of the salts, (3) the decrease in the association due to addition of salts seems to be independent on the nature of the cation or the anion, and (4) in contrast to most γ-CD complexes, the association constants between 12-crown-4 and γ-CD are nearly identical in pure D₂O and in 80:20 (v/v) CD₃OD/D₂O and only slightly lower in pure DMSO-d₆, suggesting that the hydrophobic interaction is not the main driving force for complexation in these systems. The pH has only a nonsignificant effect on the association constant of the γ-CD:12C4 complex. Plausible explanations for the above observations and the advantages and disadvantages of NMR diffusion measurements for determination of association constants are discussed.