Crystal Structures of Antiarrhythmic Drug Disopyramide and Its Salt with Phthalic Acid

Disopyramide (DPA) is as a class IA antiarrhythmic drug and its crystallization from cyclohexane at ambient condition yields lower melting form crystals which belong to the monoclinic centrosymmetric space group P2(1)/n, having two molecules in an asymmetric unit. Crystal structure analysis of pure DPA revealed closely associated DPA molecules aggregates via amide-amide dimer synthon through the N-H center dot center dot center dot O hydrogen bond whereas the second amide hydrogen N-H engaged in an intramolecular N-H center dot center dot center dot N hydrogen bond with N-nitrogen of 2-pyridine moieties. Crystallization of DPA and phthalic acid (PA) in 1: 1 stoichiometric molar ratio from acetone at ambient condition yielded block shape crystals of 1:1 DPA_PA salt. Its X-ray single crystal structure revealed the formation of salt by transfer of acidic proton from one of the carboxylic acidic groups of PA to the tertiary amino group of chain moiety (N3-nitrogen atom) of DPA molecules. DPA_PA salt crystals belong to the monoclinic centrosymmetric space group P2(1)/n, comprising one protonated DPA and one PA over bar anion (hydrogen phthalate counterion) in an asymmetric unit and linked by N-H center dot center dot center dot O and C-H center dot center dot center dot O hydrogen bonds. Pure DPA and DPA_PA salt were further characterized by differential calorimetric analysis, thermal gravimetric analysis, powder x-ray diffraction and infrared spectroscopy.

Automated summary

Disopyramide (DPA) is a class IA antiarrhythmic drug, and its crystallization with phthalic acid (PA) forms a salt with specific hydrogen bonding structure; pure DPA and DPA_PA salt were further characterized by various experimental methods.