Exploring halide anion affinities to native cyclodextrins by mass spectrometry and molecular modelling

The binding affinities of cyclodextrins complexation with chlorine (Cl-), bromine (Br-) and iodine (I-), were measured by mass spectrometric titrimetry, and the fitting of the binding constants was based on the concentration measurement of the cyclodextrin equilibrium. The binding constants (lg K-a) for alpha(-), beta(-) or gamma(-) cyclodextrin with Cl- were 3.99, 4.03 and 4.11, respectively. The gas-phase binding affinity of halide anions for native cyclodextrins was probed by collision-induced dissociation. In collision-induced dissociation, the centre-of-mass frame energy results revealed that in the gas phase, for the same type of cyclodextrin, the stability of the complexes decreased in order: Cl > Br > I, and for the same halide anion, the binding stability of the complex with alpha(-), beta(-) or gamma(-)cyclodextrin decreased in the order: gamma-cyclodextrin> beta-cyclodextrin> alpha-cyclodextrin. The density functional theory calculations showed that halide anion binding on the primary face had a lower energy than the secondary face and hydrogen bonding was the main driving force for complex formation. The higher stability of the gamma-cyclodextrin complex with the Cl anion can be attributed to the higher charge density of the Cl anion and better flexibility of gamma-cyclodextrin.