Polymorphism in β-cyclodextrin–benzoic acid inclusion complex: a kinetically controlled crystal growth according to the Ostwald’s rule

Abstract

Crystal form II of the β-cyclodextrin–benzoic acid (β-CD–BA) inclusion complex was obtained from the 1.5-year stored aqueous EtOH solution of β-CD and BA as 2β-CD·1.5BA·0.7EtOH·21H 2O in the monoclinic space group C2 with unit cell constants: a = 19.413(3), b = 24.306(4), c = 32.975(1) Å, β = 104.41(1)°. By contrast, the desired crystal form I in the triclinic space group P1 that ever grew up from the fresh solution as 2β-CD·2BA·0.7EtOH·20.65H 2O was not reproducible any more [Aree, T.; Chaichit, N. Carbohydr. Res. 2003, 338, 439–446]. In the two crystal forms, β-CDs are isostructural with a ‘round’ conformation stabilized by intramolecular O-3( n)⋯O-2( n + 1) hydrogen bonds. The BA inclusion geometries are similar with a preferred orientation, that is, BAs are situated above the O-4 plane, point their COOH groups to the β-CD O-6 side, incline 52° with respect to the O-4 plane and are mainly maintained in positions by hydrogen bonding with the surrounding water molecules. β-CDs form dimers as structural motif of different packing modes: the screw-channel type in form II and the average of intermediate and tetrad types in form I. Polymorphism in the β-CD–BA inclusion complex is a kinetically controlled crystal growth following the Ostwald’s rule: the less stable crystal form I grew up first within one week from the fresh solution, whereas the more stable crystal form II appeared after 1.5-year storage.