Crystal structure, interaction energies and experimental electron density of the popular drug ketoprophen.

ABSTRACT: The crystal and molecular structure of the pure (S)-enantiomer of the popular analgesic and anti-inflammatory drug ketoprophen (?-ket) is reported. A detailed aspherical charge-density model based on high-resolution X-ray diffraction data has been refined, yielding a high-precision geometric description and classification of the O-H?O interactions as medium strength hydrogen bonds. The crystal structure of the racemic form of ketoprophen (?-ket) was also redetermined at 100?K, at 0.5?Å resolution. A previously unreported disorder (10% occupancy) was discovered. In contrast to the racemic ?-ket case, the (S)-enantiomer crystallizes with two independent molecules in the asymmetric unit with two distinct conformations. The major difference between the ?-ket and ?-ket crystal forms lies in the formation of distinct hydrogen-bonded motifs: a closed ring motif in ?-ket versus infinite chains of hydrogen bonds in the chiral ?-ket structure. However, the overall crystal packing of both forms is surprisingly similar, with close-packed layers of antiparallel-oriented benzo-phenone moieties bound by C-H?? interactions. Notably, the most important stabilizing term in the total lattice energies in both instances proved to be the dispersion related to these interactions. Both forms of the title compound (?- and ?-ket) were additionally characterized by differential scanning calorimetry and thermogravimetric analysis.

SUBMITTER: Pawledzio S 

PROVIDER: S-EPMC6211533 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature