title: Structural relationships, thermal properties, and physicochemical characterization of anhydrous and solvated crystalline forms of tetroxoprim.
abstract: Six distinct phases of the antibacterial tetroxoprim (TXP) have been isolated by recrystallization from various solvents. These comprise two polymorphs, forms I and II, and four solvates with the following solvents and TXP solvent stoichiometric ratios: chloroform (3:2), water (3:2), methanol (2:1), and ethanol (2:1). Thermal and infrared spectral data showed that forms I and II are enantiotropically related with form II being stable below the transition temperature of 118 degrees C and form I melting at 159 degrees C. The crystal structure of form I contains three crystallographically independent TXP molecules arranged in layers formed by extensive base pairing between the 2,4-diaminopyrimidine rings. This species invariably results upon heating the solvates of TXP. Thermogravimetry and differential scanning calorimetry respectively showed one-step mass losses and progressively increasing desolvation temperatures for the solvates with chloroform, water, ethanol, and methanol. X-ray diffraction studies revealed that the latter three solvates are isostructural, belonging to the class of "isolated site" solvates. Extensive base pairing maintains the common TXP crystalline framework. Thermal data for the desolvation of these phases are reconciled with the observed crystal packing features. Experimental and computed powder X-ray patterns for form I and the solvates with water, methanol, and ethanol are presented.
authors.affiliation: University of Cape Town, Department of Chemistry, P. D. Hahn Building, Room B 201, Private Bag, Rondebosch 7701, South Africa. xraymino@science.uct.ac.za
authors.forename: Mino R
authors.initials: MR
authors.lastname: Caira
authors.forename: Giampiero
authors.initials: G
authors.lastname: Bettinetti
authors.forename: Milena
authors.initials: M
authors.lastname: Sorrenti
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003460:Crystallization; D018360:Crystallography, X-Ray; D011743:Pyrimidines / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D013818:Thermogravimetry / Q000379:methods
chemical_list: D000890:Anti-Infective Agents; D011743:Pyrimidines; D012997:Solvents; C023507:tetroxoprim