Triple Structural Transition below Room Temperature in the Antifilarial Drug Diethylcarbamazine Citrate

Abstract

A very unusual triple structural transition pattern below room temperature was observed for the antifilarial drug diethylcarbamazine citrate. Besides the first thermal, crystallographic, and vibrational investigations of this first-line drug used in clinical treatment for lymphatic filariasis, a noteworthy behavior with three structural transformations as a function of temperature was demonstrated by differential scanning calorimetry, Raman spectroscopy, and single-crystal X-ray diffractometry. Our X-ray data on single crystals allow for a complete featuring and understanding of all transitions, since the four structures associated with the three solid−solid phase transformations were accurately determined. Two of three structural transitions show an order−disorder mechanism and temperature hysteresis with exothermic peaks at 224 K (T1′) and 213 K (T2′) upon cooling and endothermic ones at 248 K (T1) and 226 K (T2) upon heating. The other transition occurs at 108 K (T3) and it is temperature-rate sensitiv...