title: Cocrystals of the antibiotic trimethoprim with glutarimide and 3,3-dimethylglutarimide held together by three hydrogen bonds.
abstract: The antibiotic trimethoprim [5-(3,4,5-trimethoxybenzyl)pyrimidine-2,4-diamine] was cocrystallized with glutarimide (piperidine-2,6-dione) and its 3,3-dimethyl derivative (4,4-dimethylpiperidine-2,6-dione). The cocrystals, viz. trimethoprim-glutarimide (1/1), C14H18N4O3·C5H7NO2, (I), and trimethoprim-3,3-dimethylglutarimide (1/1), C14H18N4O3·C7H11NO2, (II), are held together by three neighbouring hydrogen bonds (one central N-H...N and two N-H...O) between the pyrimidine ring of trimethoprim and the imide group of glutarimide, with an ADA/DAD pattern (A = acceptor and D = donor). These heterodimers resemble two known cocrystals of trimethoprim with barbituric acid and its 5,5-diethyl derivative. Trimethoprim shows a conformation in which the planes of the pyrimidine and benzene rings are approximately perpendicular to one another. In its glutarimide coformer, five of the six ring atoms lie in a common plane; the C atom opposite the N atom deviates by about 0.6 Å. The crystal packing of each of the two cocrystals is characterized by an extended network of hydrogen bonds and contains centrosymmetrically related trimethoprim homodimers formed by a pair of N-H...N hydrogen bonds. This structural motif occurs in five of the nine published crystal structures in which neutral trimethoprim is present.
authors.affiliation: Institut für Organische Chemie und Chemische Biologie, Goethe-Universität Frankfurt, Max-von-Laue-Strasse 7, 60438 Frankfurt am Main, Germany.
authors.forename: Quoc Cuong
authors.initials: QC
authors.lastname: Ton
authors.affiliation: Institut für Organische Chemie und Chemische Biologie, Goethe-Universität Frankfurt, Max-von-Laue-Strasse 7, 60438 Frankfurt am Main, Germany.
authors.forename: Ernst
authors.initials: E
authors.lastname: Egert
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003959:Diamines / Q000737:chemistry*; D006860:Hydrogen Bonding; D008968:Molecular Conformation; D010881:Piperidones / Q000737:chemistry*; D014295:Trimethoprim / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D003959:Diamines; D010881:Piperidones; D014295:Trimethoprim; C007864:glutarimide
keywords: active pharmaceutical ingredients; antibiotics; cocrystal; crystal structure; glutarimide; hydrogen bonds; molecular recognition; trimethoprim