Beta-cyclodextrin inclusion complexes: effect of the host substitution on molecular recognition

The stability of inclusion complexes (i.e. the measure of molecular recognition between a guest and beta-cyclodextrin) is highly influenced by the fit of the guest into the cavity of the host and by the secondary bonds among the functional groups getting in close connection. The strength of these interactions depend on the size, shape and functional groups of the guests as well as on the facts that both the size of the cavity and the reactivity of beta-cyclodextrins are altered when the hydroxy groups are substituted. As best models, the interactions among hydroxypropylated cyclodextrins of different average degree (and pattern) of substitution and phenolphthalein (as a model for "large" guests) and p-nitrophenol-p-nitrophenolate couple (as for "small" ones) have been studied. The formation constants of phenolphthalein hydroxypropyl-beta-cyclodextrin complexes are continuously decreasing, while those of p-nitrophenol/phenolate ones show a maximum with increasing degree of substitution. The pattern of substitution has also a significant effect on the quality of the interactions: the substitution on O(6) position alters the type of the interactions most, and a series of different findings prove that this change is the basis in the chiral selectivity of different cyclodextrin derivatives, too.