The antibiotic cephalexin [systematic name: d-7-(2-amino-2-phenylacetamido)-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]-oct-2-ene-2-carboxylic acid] forms a range of isomorphic solvates, with the maximum hydration state of two water molecules formed only at high relative humidities. The water content of the structure reported here (C 16 H 17 N 3 O 4 SÁ1.9H 2 O) falls just short of this con®guration, having three independent cephalexin molecules, one of which is disordered, and 5.72 observed water molecules in the asymmetric unit. The facile nature of the cephalexin solvation/desolvation process is found to be facilitated by a complex channel structure, which allows free movement of solvent in the crystallographic a and b directions. CommentThe cephalosporin derivative cephalexin (CEX) is an antibiotic useful for treating a variety of infections, including those of the respiratory tract, of the skin and of other soft tissues. The characterization of the solid-state properties of CEX has, however, been hampered by uncertainty over the exact nature of its hydration behaviour. CEX can form a range of hydrates in the solid state, all with essentially identical unit cells, and has thus been identi®ed as part of the class of compounds known as isomorphic desolvates (Stephenson et al., 1998). Indeed, CEX is known to go further and reversibly replaces water with other small, polar, solvent molecules (Pfeiffer et al., 1970). Powder diffraction studies show that the isomorphic solvates have similar unit-cell dimensions but, despite their crystallographic similarities, their commercially important physical properties (such as their solubilities and dehydration behaviour) vary considerably. Despite considerable interest in CEX, no single-crystal structure determination had previously been achieved, and so the structural basis of its ready solvation/desolvation process remained unknown. However, we have overcome the problems of small crystal size and loss of (single) crystallinity upon facile dehydration by utilizing careful sample preparation methods (see Experimental) and the extra intensity of synchrotron radiation to report here the ®rst crystal structure of any CEX hydrate, that of CEXÁ1.9H 2 O, (I).The asymmetic unit of (I) was found to contain three CEX molecules and, spread over ten sites, 5.72 water molecules. The three crystallographically independent molecules of CEX (Fig. 1) were found to exist in the zwitterionic form, with no signi®cant differences in their bond lengths or angles. One CEX molecule is disordered. There is some¯exibility in the amide backbone, with the OÐCÐCÐN(H 3 ) torsion angles ranging from 27.3 (6) to 44.5 (6) . The geometry of the related species cefadroxil (Shin & Cho, 1992) has a similar conformation, ®tting within the range found here for CEX, as does CEX complexed with -napthol (Kemperman et al., 1999), although here the amide backbone is more eclipsed (equivalent angle = 16.2 ).That the stochiometrically exact dihydrate is not found is unsurprising, given the steep gradient observed by Ste...
We thank Dr K. Mackenzie who conceived the research programme, executed preparative and kinetic work, and provided excellent quality crystals. Dr R. Siedlecka is thanked for the preparation of compound (2D). CW thanks the Institut Laue-Langevin for a studentship.Supplementary data for this paper are available from the IUCr electronic archives (Reference: CF1209). Services for accessing these data are described at the back of the journal. Strathclyde, Glasgow G1 1XL Scotland. E-mail: a. r. kennedy @ ccsun, strath, ac. uk (Received 17 July 1997; accepted 12 November 1997) AbstractThe structure of monoclinic anhydrous 5-nitrouracil, C4H3N304, and of the solvate 5-nitrouracil dimethyl sulfoxide, C4H3N304.C2H6OS, are presented and compared with the previously known structures of the orthorhombic anhydrous form and the monohydrate. Comment 5-Nitrouracil (5NU) is currently of prime interest to the non-linear optical community (Puccetti et al., 1993; Youping et al., 1992) and is also of relevance to the biological and pharmaceutical sciences (Rao et al., 1995; Perrier & Bym, 1982). Interest in the manufacture and desolvation processes of 5NU led us to investigate the crystal growth and stability of the 5NU system from its favoured industrial solvents, water and dimethyl sulfoxide (DMSO). Two crystalline forms had previously been reported, namely, an optically active orthorhombic anhydrate, (I) (Pierce & Wing, 1986), and a monoclinic monohydrate, (II) (Craven, 1967). We found that aqueous solution growth gave a mixture not only of these known polymorphs but also of a third, a monoclinic anhydrate, (HI). In addition, growth from DMSO and aqueous DMSO solutions gave a DMSO-solvated form, (IV). The structures of these new polymorphs are discussed as are the relationships between all four forms.The crystal structures exhibit extensive hydrogenbonding networks (Tables 3 and 6; Figs. 1 and 2) and it is here that the major differences between the polymorphs lie. In 5NU.DMSO, formal hydrogen bonding exists only between the N--H moieties of 5NU and the sulfoxide of the solvent; there are no 5NU to 5NU bonds, for example. This leads to the layered structure shown in Fig. 2. In contrast, the hydrated structure has dimeric hydrogen-bonded 5NU units linked in sheets by both 5NU---H20 and 5NU...5NU interactions. In (III), hydrogen bonding occurs about inversion centres, such that each 5NU molecule has four individual hydrogen bonds involving two adjacent molecules. This contrasts with (I), where each 5NU molecule is hydrogen bonded to four adjacent molecules. The differing intermolecular interactions seem to have little effect on the molecular structures of the 5NU moiety, with all bond lengths and angles being in good agreement. The main conformational difference is evident in the large twist of the NO2 group away from the plane of the ring in 5NU.DMSO, whereas it approaches coplanarity in the other three forms [dihedral angle between the least-squares planes of the ring and the NO2 group: 4.7, 2.0, 7.0(1) and 16.8 (1) ° f...
The antibiotic cephalexin [systematic name: d-7-(2-amino-2-phenylacetamido)-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]-oct-2-ene-2-carboxylic acid] forms a range of isomorphic solvates, with the maximum hydration state of two water molecules formed only at high relative humidities. The water content of the structure reported here (C 16 H 17 N 3 O 4 SÁ1.9H 2 O) falls just short of this con®guration, having three independent cephalexin molecules, one of which is disordered, and 5.72 observed water molecules in the asymmetric unit. The facile nature of the cephalexin solvation/desolvation process is found to be facilitated by a complex channel structure, which allows free movement of solvent in the crystallographic a and b directions. CommentThe cephalosporin derivative cephalexin (CEX) is an antibiotic useful for treating a variety of infections, including those of the respiratory tract, of the skin and of other soft tissues. The characterization of the solid-state properties of CEX has, however, been hampered by uncertainty over the exact nature of its hydration behaviour. CEX can form a range of hydrates in the solid state, all with essentially identical unit cells, and has thus been identi®ed as part of the class of compounds known as isomorphic desolvates (Stephenson et al., 1998). Indeed, CEX is known to go further and reversibly replaces water with other small, polar, solvent molecules (Pfeiffer et al., 1970). Powder diffraction studies show that the isomorphic solvates have similar unit-cell dimensions but, despite their crystallographic similarities, their commercially important physical properties (such as their solubilities and dehydration behaviour) vary considerably. Despite considerable interest in CEX, no single-crystal structure determination had previously been achieved, and so the structural basis of its ready solvation/desolvation process remained unknown. However, we have overcome the problems of small crystal size and loss of (single) crystallinity upon facile dehydration by utilizing careful sample preparation methods (see Experimental) and the extra intensity of synchrotron radiation to report here the ®rst crystal structure of any CEX hydrate, that of CEXÁ1.9H 2 O, (I).The asymmetic unit of (I) was found to contain three CEX molecules and, spread over ten sites, 5.72 water molecules. The three crystallographically independent molecules of CEX (Fig. 1) were found to exist in the zwitterionic form, with no signi®cant differences in their bond lengths or angles. One CEX molecule is disordered. There is some¯exibility in the amide backbone, with the OÐCÐCÐN(H 3 ) torsion angles ranging from 27.3 (6) to 44.5 (6) . The geometry of the related species cefadroxil (Shin & Cho, 1992) has a similar conformation, ®tting within the range found here for CEX, as does CEX complexed with -napthol (Kemperman et al., 1999), although here the amide backbone is more eclipsed (equivalent angle = 16.2 ). That the stochiometrically exact dihydrate is not found is unsurprising, given the steep gradient observed by ...
This paper presents novel information on the thermal dehydration and rehydration of the molecular solid, Oxalic Acid Dihydrate. Although the procedure of the overall decomposition process is welldefined, the structural basis and mechanism of the dehydration process has been poorly studied. We show that the dehydration occurs in a planar manner, with a resultant semi-topotactic relationship between hydrated and dehydrated structures, reflected in the molecular packing. During rehydration, the reconstruction of the phase can be seen to occur at a 3-dimensional phase boundary reaction front, i.e. a recrystallisation of the dihydrate on the surface of the reactant product, with the topotactic relationship leading to texturing and possibly epitaxial relationships between partially dehydrated and rehydrated structures. The proposed mechanism is shown to be consistent with the measured kinetics of the process.
The crystallization of 5-nitrouracil (5NU) from pure aqueous solution yields two anhydrous polymorphs and a monohydrate depending on the temperature at which the process is carried out. 5NU mimics true polymorphism in that, when retained in aqueous solution, both metastable (anhydrous) forms undergo solvent mediated phase transformations (SMPTs) into the more thermodynamically stable hydrated form as would be predicted by Ostwald's rule of stages. The phase transformations can occur either in the classical manner of dissolution and recrystallization or, in one case, may in some circumstances be nucleated and morphologically templated by the original crystalline form. There is no appearance from aqueous solution of a known third acentric anhydrous form, previously prepared from acetonitrile solutions. Preliminary experiments suggest this nonappearance may result from the relatively high solubility of this form in aqueous solution.
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