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

IUCrJ

Pawldzio, S.¹ 

[1] Biological and Chemical Research Centre, Department of Chemistry, University of Warsaw, wirki i Wigury 101, Warsaw 02-089, Poland

关键词: KETOPROPHEN;    CHARGE DENSITY;    CRYSTAL STRUCTURES;    PHARMACEUTICALS;    BIOINVERSION;   

DOI  :  10.1107/S2052252518013222

学科分类：数学（综合）

来源: International Union of Crystallography

【 摘 要 】

The crystal and molecular structure of the pure (S)-enantiomer of the popular analgesic and anti-inflammatory drug ketoprophen (α-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 (β-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 β-ket case, the (S)-enantiomer crystallizes with two independent molecules in the asymmetric unit with two distinct conformations. The major difference between the β-ket and α-ket crystal forms lies in the formation of distinct hydrogen-bonded motifs: a closed ring motif in β-ket versus infinite chains of hydrogen bonds in the chiral α-ket structure. However, the overall crystal packing of both forms is surprisingly similar, with close-packed layers of antiparallel-oriented benzo­phenone moieties bound by C—H⋯π 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 (α- and β-ket) were additionally characterized by differential scanning calorimetry and thermogravimetric analysis.

【 授权许可】

CC BY