Structures of Polymorphic Agomelatine and Its Cocrystals with Acetic Acid and Ethylene Glycol

Abstract

Two polymorphic structures of Form II and Form III of agomelatine were determined by single and powder X-ray diffraction, respectively, in which the agomelatine molecules are linked through the intermolecular hydrogen bonding interactions to form a one-dimensional (1D) chain, and the 1D chains are further packed through interchain π···π and C−H···π interactions to generate the three-dimensional (3D) structures. Two agomelatine cocrystals with acetic acid ( 1 ) and ethylene glycol ( 2 ) were synthesized, and their structures were determined by single and powder X-ray diffraction, respectively, in which the acetic acid molecules in 1 alternately link the agomelatine molecules to form 1D right-handed and left-handed helical chains, while the alternately linking of agomelatine molecules by ethylene glycol molecules in 2 generates the homochiral right-handed helical chains. After the formation of cocrystals of 1 and 2, the melting points dramatically decrease, and the solubility is approximately twice as large as that of Form II.