Do Cyclodextrins Aggregate in Water? Insights from NMR Experiments.

One decade ago Bonini et al. [Langmuir 2006, 22, 1478-1484] reported the occurrence of aggregates of β-cyclodextrin in aqueous solutions with sizes in the range from 90 nm to a few micrometers. The experimental technique used was cryo-TEM. This work followed a number of previous studies involving other physical parameters, such as viscosities and activity coefficients, the results of which were interpreted in terms of self-aggregation of cyclodextrins. Since then, the ability of cyclodextrins to self-assemble were often used to explain and rationalize the supramolecular mechanisms involving cyclodextrins. Here, the question of aggregation of native cyclodextrins (α-, β-, and γ-) in aqueous solutions is addressed by using (1)H NMR techniques, including NMR diffusometry, relaxometry, and proton peak intensities. Within the detection limit of the NMR experiments, no aggregates of cyclodextrin were observed. If aggregates are present, the fraction of cyclodextrin in aggregates is quite small-less than 1%. However, we cannot exclude the presence of transient clusters involving several cyclodextrin molecules where the lifetime of the cluster is short.