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ABSTRACT: An experimental search for physical forms of the thiazide diuretic compound chlorothiazide comprising 402 different crystallizations identified one nonsolvated form and ten crystalline solvates. There are five distinct conformations in the experimental crystal structures which are in good agreement with the conformational minima found by ab initio optimization of the isolated molecule structure. An approximate rigid-body crystal energy landscape using these five conformations produced a diverse range of low energy crystal structures, with the anhydrous structure among the most stable. Inspection of the molecular packing adopted in both the experimental and predicted structures highlighted a number of chlorothiazide···chlorothiazide motifs that result from packing the different conformers. Specifically, four bimolecular face-to-face motifs were observed in most of the predicted structures and all of the experimental structures. The role of these robust intermolecular packing motifs and of the organic solvent molecules in stabilizing the experimental solvate structures of chlorothiazide is discussed. The results highlight the value of the approximate crystal energy landscape for flexible organic molecules in assisting with the interpretation of solid-state diversity in chlorothiazide crystal structures and identifying key stabilizing packing features.
01/2011;
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Angewandte Chemie International Edition 10/2010; 49(47):8892-6. · 13.45 Impact Factor
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ABSTRACT: Urea forms a 1:1 solvate with N,N-dimethyl-acetamide (DMA) [systematic name: diamino-methanal-N,N-dimethyl-acetamide (1/1), C(4)H(9)NO·CH(4)N(2)O] with both mol-ecules positioned on a twofold axis, giving rise to rotational disorder of the DMA mol-ecule. The mol-ecules display a layered structure in which urea mol-ecules form hydrogen-bonded ribbons bounded by mol-ecules of solvent.
Acta Crystallographica Section E Structure Reports Online 01/2008; 64(Pt 2):o355. · 0.35 Impact Factor
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ABSTRACT: Hydrogen chloride gas (HCl) is absorbed (and reversibly released) by a nonporous crystalline solid, [CuCl2(3-Clpy)2] (3-Clpy = 3-chloropyridine), under ambient conditions leading to conversion from the blue coordination compound to the yellow salt (3-ClpyH)2[CuCl4]. These reactions require substantial motions within the crystalline solid including a change in the copper coordination environment from square planar to tetrahedral. This process also involves cleavage of the covalent bond of the gaseous molecules (H-Cl) and of coordination bonds of the molecular solid compound (Cu-N) and formation of N-H and Cu-Cl bonds. These reactions are not a single-crystal-to-single-crystal transformation; thus, the crystal structure determinations have been performed using X-ray powder diffraction. Importantly, we demonstrate that these reactions proceed in the absence of solvent or water vapor, ruling out the possibility of a water-assisted (microscopic recrystallization) mechanism, which is remarkable given all the structural changes needed for the process to take place. Gas-phase FTIR spectroscopy has permitted us to establish that this process is actually a solid-gas equilibrium, and time-resolved X-ray powder diffraction (both in situ and ex situ) has been used for the study of possible intermediates as well as the kinetics of the reaction.
Journal of the American Chemical Society 01/2008; 129(50):15606-14. · 9.91 Impact Factor
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ABSTRACT: Bendroflumethiazide, or 3-benzyl-6-(trifluoromethyl)-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide, is reported to crystallize as 1:1 solvates with acetone, C(15)H(14)F(3)N(3)O(4)S(2).C(3)H(6)O, and N,N-dimethylformamide, C(15)H(14)F(3)N(3)O(4)S(2).C(3)H(7)NO. A detailed investigation of the crystal packing and intermolecular interactions is presented by means of Hirshfeld surface analysis. This analysis confirms the atomic positions of methyl H atoms of the solvent molecules that were inferred from the X-ray data and provides a useful tool for structure validation.
Acta crystallographica. Section C, Crystal structure communications 12/2007; 63(Pt 11):o659-63. · 0.78 Impact Factor
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ABSTRACT: The crystal structures of gamma-carbamazepine (P1, Z' = 4) and chlorothiazide N,N-dimethylformamide solvate (1/2) (P2(1)/c, Z' = 2) have been determined from synchrotron and laboratory X-ray powder diffraction data, respectively, using simulated annealing. Both structures represent a significant challenge for global optimization and the successful solutions and subsequent refinements highlight the ever-expanding range of applicability of powder diffraction to structural problems of pharmaceutical relevance.
Journal of Pharmaceutical Sciences 06/2007; 96(5):1192-202. · 3.06 Impact Factor
