Kinetics of acetal and orthobenzoate hydrolysis as probes of cyclodextrin-guest binding
Acid-catalyzed hydrolysis of acetophenone dimethyl acetal (ADMA) and trimethyl orthobenzoate (TMOB) is retarded by cyclodextrins (CDs): α-CD, β-CD, hb-β-CD = "hydroxypropyl-β-cyclodextrin", and γ-CD. The observed first order rate constants (kobs) vary with [CD] in the manner expected for 1:1 binding between the substrates and the CDs. Similar behaviour was found recently for the hydrolysis of benzaldehyde dimethyl acetal (BDMA). With β-CD and hp-β-CD, the binding of all three substrates (BDMA, ADMA, TMOB) is strong and the CD-bound forms have very little reactivity. By contrast, substrate binding by α-CD is much weaker, and the CD-bound forms have appreciable, though reduced, reactivity. Substrate binding by γ-CD is also relatively weak, but the bound substrates have very low reactivities. The hydrolysis reactions of ADMA, TMOB, and BDMA have been evaluated as kinetic probes of the binding of guests to CD hosts. For α-CD, β-CD, and hp-β-CD, the addition of guests reduces the amount of free CD and thereby alleviates retardation of the hydrolysis by the CD. The resultant increases in hydrolysis rates can be analyzed to provide estimates of CD-guest dissociation constants, KG. For aliphatic alcohols and ketones binding to β-CD and hp-β-CD, all three probe reactions provide values of KG that agree well with each other and with literature values determined by other methods. The approach does not work well with α-CD because of its much weaker binding of the kinetic probes and their less pronounced dependence of kobs on [α-CD]. In the case of γ;-CD, the approach cannot be used because added guests cause a further lowering in the rate of hydrolysis, suggesting the formation of an unreactive ternary (substrate·CD·guest) complex.Key words: acetal, hydrolysis, cyclodextrin, host-guest, binding.