Influence of ion valency on aggregation and inclusion behaviour of β-cyclodextrin and its derivatives in aqueous solution.

Cyclodextrins (CDs) exhibit concentration-dependent aggregation in aqueous solution governed by substitution chemistry, hydration, and intermolecular interactions. In this study, the aggregation behaviour of β-cyclodextrin (β-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD), and sulfobutyl ether-β-cyclodextrin (SBE-β-CD) was systematically investigated in the presence of monovalent (K+) and divalent (Ca2+) electrolytes using dynamic light scattering, conductivity, surface tension, and phenolphthalein inclusion measurements. Under salt-free conditions, β-CD showed pronounced aggregation driven by intermolecular hydrogen bonding, SBE-β-CD displayed coexistence of molecular and aggregated populations consistent with its charged substituents, and HP-β-CD remained largely dispersed due to steric and hydration effects. Electrolyte addition modified aggregation trends in a valency-dependent manner. K+ produced moderate changes consistent with electrostatic screening, whereas Ca2+ induced stronger and time-dependent aggregation effects. Conductivity measurements reflected electrolyte-dependent modification of the ionic environment, while surface tension data supported changes in aggregation state. Phenolphthalein inclusion assays demonstrated that electrolyte-induced aggregation correlates with variations in effective cavity accessibility. These results provide comparative physicochemical insight into how substitution pattern and ion valency influence aggregation and host-guest behaviour of cyclodextrins in aqueous solution.