Stoichiometric and microenvironmental effects on hydrolysis of propantheline and oxyphenonium bromides in cyclodextrin solutions

The effects of alpha-, beta-, and gamma -cyclodextrins (CDs) on the basic h ydrolysis of propantheline bromide (PB) and oxyphenonium bromide (OB) are a nalyzed in terms of the stoichiometry and microenvironments of their comple xes. The rate constant of each species is evaluated with binding constant d ata for the 1:1, 1:2, and 2:1 complexes. The dielectric constant of the bin ding site of PB is estimated from the ultraviolet maximum wavelength in ref erence with the ethanol-water and dioxane-water systems. The energy-optimiz ed structures of some complexes of PB with beta- and gamma -CD are obtained by molecular mechanics. Because the ester linkage of PB in the 1:1 complex with alpha -CD and in the 2:1 complex with gamma -CD is located near hydro xyls of the CD rim, these complexes catalyze the hydrolysis of PB. In contr ast, the hydrolysis is inhibited by the formation of the 1:1 and 1:2 comple xes of beta -CD and the 1:1 complex of gamma -CD because the ester linkage of PB is rather deeply incorporated into the CD cavities for these complexe s. All the CDs inhibit the hydrolysis of OB. The rate constant of the 1:1 c omplex of OB and CD is in the decreasing order alpha -CD > gamma -CD > beta -CD. This order is consistent with that of the local dielectric constants of the binding sites. (C) 2001 Wiley-Liss, Inc. and the American Pharmaceut ical Association J Pharm Sci 90:740-748, 2001.