Crystal structures of antiarrhythmic drug disopyramide and its salt with phthalic acid

Majid Ismail Tamboli, Yushi Okamoto, Yohei Utsumi, Takayuki Furuishi, Siran Wang, Daiki Umeda, Okky Dwichandra Putra, Kaori Fukuzawa, Hidehiro Uekusa, Etsuo Yonemochi

Research output: Contribution to journalArticlepeer-review

Abstract

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 P21/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···O hydrogen bond whereas the second amide hydrogen N–H engaged in an intramolecular N–H···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 P21/n, comprising one protonated DPA and one PA¯ anion (hydrogen phthalate counterion) in an asymmetric unit and linked by N–H···O and C–H···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.

Original languageEnglish
Article number379
JournalCrystals
Volume11
Issue number4
DOIs
Publication statusPublished - 2021 Apr

Keywords

  • Crystal structure
  • Disopyramide
  • Metastable
  • Phthalic acid
  • Salt

ASJC Scopus subject areas

  • Chemical Engineering(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Inorganic Chemistry

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