Crystal Structure and Toxicity of the Polymorphic Modifications of the Rodenticide Difenacin

Abstract

Two new polymorphic forms (I and II) of 2-(diphenylacetyl)indanedione-1,3 (C23H16O3, difenacin, DF) were obtained by original methods. The crystal structures of the polymorphic forms, solved by X‑ray diffraction (XRD) analysis, were compared with those of the known modification III. The structure of the latter was re-determined and studied at a low temperature. The crystal parameters of the polymorphic forms of DF are: (I) Pna21: a = 8.549(2) Å, b = 35.323(7) Å, and c = 5.803(1) Å; Z = 4; (II) P21/c: a = 25.856(1) Å, b = 12.363(1) Å, and c = 16.081(1) Å; β = 94.00(1)°; Z = 12; (III) P21/n: a = 10.365(2) Å, b = 12.239(2) Å, and c = 13.227(2) Å; β = 95.83(1)°; Z = 4. For samples I and II, the recording was performed at room temperature; for III, at 173 K. The number of independent molecules in the polymorphs was found to be different: one molecule in I and III, and three in II. In difenacin crystals, the conformation of neutral C23H16O3 molecules is stabilized by intramolecular hydrogen bonding, with the enol proton localized near the oxygen atom of the keto group of the acyl fragment. The crystal packings contain various sets of C–H···O contacts and intermolecular π–π stacking interactions of indanedionate fragments, with interplanar distances varying from 3.50 to 3.65 Å. The C23H16O3 molecule does not contain a chiral center, but the phenyl groups in the acyl substituent in the crystals are nonequivalent, which should lead to optical activity (stereoisomers in equal amounts). The polymorphic forms proved equally efficient in the same dosage of 2.28 mg/kg for white rats.