Exploring the interactions between buffers and cyclodextrin complexes—formation of regular inclusion or atypical non-inclusion complexes

The aim of this study was for the first time to determine the effect of 11 buffers on a γ-cyclodextrin complex, and use these and previous reported data to systematically explore the effect of buffers on different cyclodextrin complexes, considering differences in cavity size and exterior between the cyclodextrins. The effect of 11 buffers on the binding between γ-cyclodextrin and the bile salt taurochenodeoxycholate was determined using isothermal titration calorimetry, and the stability constant of the complex ranged from 6.1 × 10⁴ to 9.0 × 10⁴ M⁻¹, depending on the buffer species. Three buffers (citric, maleic and 2-morpholinoethane-sulfonic acid) decreased the stability constant of the complex compared to the stability in water, though to a degree that has limited practical relevance. As for other cyclodextrin complexes, the stability constant depended on the buffer species present in solution. The analysis showed that the size of the cyclodextrin cavity, rather than the exterior, was paramount for the effect of carboxylic acid buffers, suggesting formation of regular inclusion complexes between carboxylic acid buffers and cyclodextrins.