Reassessment of paracetamol orthorhombic Form III and determination of a novel low-temperature monoclinic Form III-m from powder diffraction data.

Paracetamol [N-(4-hydroxyphenyl)acetamide, C8H9NO2] has several polymorphs, just like many other drugs. The most stable polymorphs, denoted Forms I and II, can be obtained easily and their crystal structures are known. Crystals of the orthorhombic, less stable, room-temperature Form III are difficult to grow; they need a special recipe to crystallize and suffer from severe preferred orientation. A crystal structure model of Form III has been proposed and solved from a combination of structure prediction and powder X-ray diffraction (PXRD) [Perrin et al. (2009). Chem. Commun. 22, 3181-3183]. The final Rwp value of 0.138 and the corresponding considerable residual trace were reasons to check its validity. A new structure determination of Form III using new high-resolution PXRD data led to a final Rwp value of 0.042 and an improvement of the earlier proposed model. In addition, a reversible phase transition was found at 170-220 K between the orthorhombic Form III and a novel monoclinic Form III-m. The crystal structure of Form III-m has been determined and refined from PXRD data to a final Rwp value of 0.059.

New furanoditerpenoids from Croton jatrophoides.

Four furanoditerpenoids were isolated from roots of Croton jatrophoides (Euphorbiaceae) collected in Tanzania. In addition to the known compounds penduliflaworosin and teucvin (mallotucin A), a new teucvin isomer, which was named isoteucvin, and a furanoditerpenoid with a new skeleton, for which the name jatrophoidin was adopted, were isolated. Their structures were elucidated by spectroscopic methods such as ESI-MS and NMR, including (1)H-, (13)C-, and two-dimensional NMR. The crystal structures of isoteucvin and jatrophoidin were solved using single-crystal X-ray diffraction, by which we also established the absolute configuration of jatrophoidin. The refined crystal structure of isoteucvin has the same (absolute) configuration as jatrophoidin, although the X-ray diffraction data of isoteucvin were not conclusive with respect to the absolute configuration.

Structures of mono-unsaturated triacylglycerols. V. The beta'(1)-2, beta'-3 and beta(2)-3 polymorphs of 1,3-dilauroyl-2-oleoylglycerol (LaOLa) from synchrotron and laboratory powder diffraction data.

The crystal structures of the beta'(1)-2, the beta'-3 and the beta(2)-3 polymorphs of 1,3-dilauroyl-2-oleoylglycerol have been solved from powder diffraction data. The packing of the beta(2)-3 polymorph is similar to that of other cis mono-unsaturated triacylglycerols. Both the beta' polymorphs are crystallized in a novel type of packing in which one of the saturated lauroyl chains is packed side-by-side with part of the unsaturated oleoyl chain.

Structures of mono-unsaturated triacylglycerols. III. The beta-2 polymorphs of trans-mono-unsaturated triacylglycerols and related fully saturated triacylglycerols.

The beta-2 crystal structures of a series of saturated and trans-mono-unsaturated triacylglycerols (TAGs) have been solved from high-resolution powder synchrotron diffraction data. The series comprises symmetric as well as asymmetric even-numbered TAGs and the trans-mono-unsaturated ones all have a single elaidoyl chain. The structures have been solved with the direct-space parallel-tempering program FOX and refined with the Rietveld program GSAS. The beta-2 structures all crystallized in the space group P\bar 1 with the same molecular conformation. Within the resolution of the data no significant difference in packing or conformation is observed between trans-mono-unsaturated TAGs and saturated (stearoyl or palmitoyl) chain-containing analogues, in spite of the lower melting points of the former. An analysis of the position of the stepped methyl end-plane in the various subgroups of TAGs confirms most but not all suppositions found in the literature.

Structures of mono-unsaturated triacylglycerols. IV. The highest melting beta'-2 polymorphs of trans-mono-unsaturated triacylglycerols and related saturated TAGs and their polymorphic stability.

The beta'(1)-2 crystal structures of a series of mixed-chain saturated and trans-mono-unsaturated triacylglycerols containing palmitoyl, stearoyl and elaidoyl acyl chains have been solved from high-resolution powder diffraction data, from synchrotron as well as laboratory X-ray sources. The structures crystallized in the space group I2 with two independent molecules forming a dimer in the asymmetric unit, and packed in double-chain length layers. Unlike the corresponding beta-2 structures the solved beta'(1)-2 structures have different molecular conformations for the symmetric and the asymmetric mixed triacylglycerols, both with the sn-2 chain in a leg position of the chair-shaped conformation. A transformation to the beta-2 structure with the sn-2 chain in the back position is complicated and unlikely to take place in the solid state. A novel beta'-2 polymorph of PSS has been crystallized and its structure has been solved. The melting point (239 K) of this so-called beta'(0)-2 polymorph is 2 K above that of the beta'(1)-2 polymorph and almost equal to that of the beta-2 polymorph of PSS. The difference in packing of the beta'(0)-2 versus beta'(1)-2 structure explains the slow beta'(1)-2 to beta'(0)-2 phase transition. The transition is strikingly similar to the beta(2)-3 to beta(1)-3 transition in cis-mono-unsaturated triacylglycerols.

Spectroscopic investigations and crystal structure from synchrotron powder data of the inclusion complex of beta-cyclodextrin with atenolol.

Inclusion complexes of atenolol with beta-cyclodextrin (beta-CD) in aqueous solution have been investigated with 1H NMR and UV-vis spectroscopy. The stoichiometry of this inclusion complex was established to be equimolar (1:1) and its stability constant was determined by UV-vis spectroscopy. The crystal structure of the beta-CD-atenolol (1:1) inclusion compound has been solved from synchrotron powder diffraction data using direct-space search techniques. The crystal structure model and 1H NMR data are in good agreement and, with support of Hyperchem MM+ molecular dynamics results, suggest which protons are likely to be involved in the inclusion process that leads to the supramolecular architecture of this guest-host complex.

Structures of tetrabromothiophene and tetrabromoselenophene: the influence of the heteroatom on the heterophene packing.

The crystal structures of C(4)Br(4)S and C(4)Br(4)Se have been determined from X-ray powder diffraction data, using direct-space search techniques. In the case of C(4)Br(4)S two crystalline phases occur, a stable orthorhombic and a metastable monoclinic phase. For the orthorhombic phase two different structural models were found that fit the experimental data equally well. The diversity in crystal structure models and packings of C(4)Br(4)S is explained.

New preparation of 1,2,4,5,7,8-hexaoxonanes.

A new versatile procedure was developed for the synthesis of 1,2,4,5,7,8-hexaoxonanes based on the Lewis acid catalyzed reaction of acetals with 1,1'-dihydroperoxydicycloalkyl peroxides. The procedure substantially extends the structural diversity of these compounds and, in most cases, allows the synthesis of these compounds in higher yields (to 96%) and with higher selectivity. Complexation of hexaoxonane with chloroform was documented for the first time. The structures of several triperoxides were established by X-ray diffraction.

Structures of mono-unsaturated triacylglycerols. I. The beta1 polymorph.

The crystal structures of the beta1 polymorphs of mono-unsaturated triacylglycerols have been solved from high-resolution laboratory and synchrotron powder diffraction data for five pure compounds, the 1,3-dimyristoyl-2-oleoylglycerol (beta1-MOM), 1,3-dipalmitoyl-2-oleoylglycerol (beta1-POP), 1,3-distearoyl-2-oleoylglycerol (beta1-SOS), 1-palmitoyl-2-oleoyl-3-stearoylglycerol (beta1-POS), 1-stearoyl-2-oleoyl-3-arachidoylglycerol (beta1-SOA) and three mixtures: the co-crystallized 1:1 molar mixture of SOS and POP [beta1-SOS/POP (1:1)] and two cocoa butters from Bahia and Ivory Coast, both in their beta-VI (=beta1) polymorph. All eight beta1 structures crystallized in the space group (P2(1)/n) and have two short cell axes (5.44-5.46 and 8.18-8.22 A), as well as a very long b axis (112-135 A). The dominant-zone problem in the indexing of the powder patterns was solved with the special brute-force indexing routine LSQDETC from the POWSIM program. Structures were solved using the direct-space parallel-tempering method FOX and refined with GSAS. Along the b axis, alternations of inversion-centre-related ;three-packs' can be discerned. Each ;three-pack' has a central oleic zone, with oleic acyl chains of the molecules being packed together, that is sandwiched between two saturated-chain zones. The conformation of the triacylglycerol molecules is relatively ;flat' because the least-square planes through the saturated chains and those through the saturated parts of the olein chain are parallel. The solution of the beta1 structures is a step forward towards understanding the mechanism of fat-bloom formation in dark chocolate and has led to a reexamination of the beta2 structural model [see van Mechelen et al. (2006). Acta Cryst. B62, 1131-1138].

Structures of mono-unsaturated triacylglycerols. II. The beta2 polymorph.

An improved crystal structure model has been established for the beta2 polymorph of the symmetric mono-unsaturated triacylglycerol 1,3-distearoyl-2-oleoylglycerol (SOS) and the equivalent beta-V polymorph of Ivory Coast cocoa butter. In addition, the crystal structures of the beta2 polymorphs are reported for the triacylglycerols 1,3-dipalmitoyl-2-oleoylglycerol (POP) and 1-palmitoyl-2-oleoyl-3-stearoylglycerol (POS), which are, together with SOS, the major components of cocoa butter, and that of 1-stearoyl-2-oleoyl-3-arachidoylglycerol (SOA). The existence of beta2-POS and beta2-SOA has not been previously reported in the literature. All structures have been solved from high-resolution laboratory or synchrotron powder diffraction data with the direct-space parallel-tempering program FOX and refined with the Rietveld module of GSAS. All compounds crystallize in similar monoclinic unit cells (Cc) with very long b axes (>127 A). The oleic chains are packed together and sandwiched between saturated chain layers, forming acyl-chain three-packs. An analysis of the beta2 polymorphs and beta1 polymorphs [van Mechelen et al. (2006). Acta Cryst. B62, 1121-1130] shows that they contain the same three-packs and differ only in the symmetry relation between the three-packs. The three-pack build-up provides an explanation of the mechanism of the phase transition that causes the formation of fat bloom on dark chocolate.

High-spin- and low-spin-state structures of [Fe(chloroethyltetrazole)6](ClO4)2 from synchrotron powder diffraction data.

The spin-crossover complex [Fe(teec)(6)](ClO(4))(2) (teec = chloroethyltetrazole) exhibits a 50 % incomplete spin crossover in the temperature range 300-30 K. Time-resolved synchrotron powder diffraction experiments have been carried out to elucidate its structural behavior. We report crystal structure models of this material at 300 K (high spin) and 90 K (low spin), as solved from synchrotron powder diffraction data by using Genetic Algorithm and Parallel Tempering techniques and refined with Rietveld refinement. During short synchrotron powder diffraction experiments (five minutes duration) two distinguishable lattices were observed the quantities of which vary with temperature. The implication of this phenomenon, that is interpreted as a structural phase transition associated with the high-to-low spin crossover, and the structural characteristics of the high-spin and low-spin models are discussed in relation to other compounds showing a similar type of spin-crossover behavior.

Low-spin state structure of [Fe(chloroethyltetrazole)6](BF4)2 obtained from synchrotron powder diffraction data.

The complex [Fe(teec)6](BF4)2 (teec = chloroethyltetrazole) shows a two-step complete spin-crossover transition in the temperature range 300-90 K. Time-resolved synchrotron powder diffraction experiments have been carried out in this temperature range, and crystal structure models have been obtained from the powder patterns by using the parallel tempering technique. Of these models, the low-spin state structure at 90 K has been refined completely with Rietveld refinement. Its structural characteristics are discussed in relation to the high-spin state model and other spin-crossover compounds. The complex shows a remarkable anisotropic unit-cell parameter contraction that is dependent on the applied cooling rate. In addition, the possible important implications for the interpretation of spin-crossover behavior in terms of structural changes are discussed.

Ammonium 3-cyano-4-(dicyanomethylene)-5-oxo-4,5-dihydro-1H-pyrrol-2-olate monohydrate.

Each anion of the title salt, NH4+.C8HN4O2-.H2O, is linked by two N-H...O hydrogen bonds to another anion, thus forming an essentially planar centrosymmetric dimer. The dimers are considered to be molecular building blocks of an anionic wall. The building blocks form infinite ribbons via -C-N...N-C- dipole-dipole and pi-pi interactions. Adjacent ribbons are stacked by means of pi-pi interactions, thus forming an anionic wall. Neighbouring walls are connected by (NH4+...H2O)n chains running along the b axis.

Structural characterization of [1,4]diazepino[6,5-b]indoles by powder diffraction.

As part of a systematic structural study of potentially pharmacologically active [1,4]diazepino[6,5-b]indoles, the crystal structures of nine compounds have been determined from laboratory powder diffraction data. The investigated compounds are: 2-oxo-1-(4-nitrophenyl)-1,2,3,6-tetrahydro[1,4]diazepino[6,5-b]indole-4-oxide, C(17)H(12)N(4)O(4) (1a); 2-oxo-1-phenyl-1,2,3,6-tetrahydro[1,4]diazepino[6,5-b]indole-4-oxide, C(17)H(13)N(3)O(2) (1b); 2-oxo-1-(4-ethoxyphenyl)-1,2,3,6-tetrahydro[1,4]diazepino[6,5-b]indole-4-oxide, C(19)H(17)N(3)O(3) (1c); 2-oxo-1-(4-chlorophenyl)-1,2,3,6-tetrahydro[1,4]diazepino[6,5-b]indole-4-oxide, C(17)H(12)N(3)O(2)Cl (1d); 2-oxo-1-(4-cyanophenyl)-1,2,3,6-tetrahydro[1,4]diazepino[6,5-b]indole-4-oxide, C(18)H(12)N(4)O(2) (1e); 6-methyl-2-oxo-1-phenyl-1,2,3,6-tetrahydro[1,4]diazepino[6,5-b]indole-4-oxide, C(18)H(15)N(3)O(2) (1f); 2-formyl-3-[N'-(omega-chloracetyl)-N'-(4-nitrophenyl)]aminoindole, C(17)H(12)N(3)O(4)Cl (2a); 2-formyl-3-[N'-(omega-chloracetyl)-N'-(4-nitrophenyl)]aminoindole solvate with toluene (2:1), C(17)H(12)N(3)O(4)Cl.0.5C(7)H(8) (2as); 2-formyl-3-[N'-(omega-chloracetyl)-N'-(4-cyanophenyl)]aminoindole, C(18)H(12)N(3)O(2)Cl (2e). Compounds (1a)-(1f) crystallize in non-centrosymmetric triclinic, monoclinic and orthorhombic space groups. The three-dimensional structures of (1a)-(1e) demonstrate identical intermolecular NH(indole)...O<--N hydrogen bonds, which form linear chains of connected molecules. A comparison of the crystal structures (2a), (2e) and (2as) shows that the solvent used in the re-crystallization of (2a) and (2e), which are intermediates in the synthesis of (1a) and (1e), affects the intermolecular hydrogen-bond formation and, as a result, leads to essentially different yields of the goal products.

Structural analysis of a melaminium polyphosphate from X-ray powder diffraction and solid-state NMR data.

The crystal structure of the environmentally friendly flame retardant melaminium polyphosphate (MPoly) (2,4,6-triamino-1,3,5-triazinium x PO(3))(n)was determined by a direct-space global optimization technique from X-ray powder diffraction data. Solid-state NMR was used to corroborate the proposed hydrogen-bonding model and to determine the average degree of polymerization (n > 100). An analysis of the crystal structure of MPoly reveals aspects of molecular geometry and packing that are characteristic for melamine-containing compounds and polyphosphate salts. A comparison of MPoly with the crystal structures of its precursors melaminium orthophosphate (MP) and melaminium dihydrogenpyrophosphate (MPy) provides insight in the mechanism of the endothermic dehydration processes that takes place in the reaction path MP --> MPy --> MPoly. Solid-state NMR characterization of various samples of the same batch showed inhomogeneities in the MPoly composition. Various quantities of orthophosphates were found, which cannot be assigned to be MP.

Structures of Fe(II) spin-crossover complexes from synchrotron powder-diffraction data.

Crystal structure determination and analysis have been carried out for the two spin-crossover compounds [Fe(teeX)(6)](BF(4))(2) (teeX is haloethyltetrazole; X = I: teei; X = Br: teeb), in both their high-spin (near 300 K) and their low-spin states (T = 90 K), using high-resolution powder-diffraction data collected at the ESRF (Grenoble, France) and SPring8 (Japan) synchrotron radiation facilities. The structures of teei have been solved using various direct-space structure determination techniques (grid search, genetic algorithm and parallel tempering) and refined with the Rietveld method using geometrical restraints. In the case of teeb, a structural model was found but a full refinement was not successful because of the presence of a significant amount of an amorphous component. Analysis of the structures (space group P2(1)/c, Z = 2) and diffraction data, and the absence of phase transitions, show the overall structural similarity of these compounds and lead to the conclusion that the gradual spin-crossovers are likely to be accompanied by small structural changes only.

N-Methylpyridinium 3-cyano-4-(dicyanomethylene)-5-oxo-4,5-dihydro-1H-pyrrol-2-olate.

The crystal structure of the title compound, C(6)H(8)N(+).C(8)HN(4)O(2)(-), is characterized by three independent ion pairs (A, B and C) in the asymmetric unit. Each ion pair consists of an anion and a cation, and the three ion pairs have similar geometric parameters. All the anions are arranged as dianion dimers via two N-H.O hydrogen bonds and the dimers form one-dimensional columns parallel to the b axis as a result of pi-pi interactions. The cations are also stacked, in two different ways: one type of stacking consists of alternating A and B cations, while the other type consists of C cations only. Each dianion dimer stack is surrounded by eight stacks of cations and is not connected directly to other dianion stacks.

N,N-dimethylanilinium 3-cyano-4-(dicyanomethylene)-5-oxo-4,5-dihydro-1H-pyrrol-2-olate.

In the title compound, C(8)H(12)N(+).C(8)HN(4)O(2)(-), the anion and cation lie on a crystallographic mirror plane and form planar ribbons via N-H...O [N...O = 2.933 (4) A, H...O = 2.01 A and N-H...O = 170 degrees] and N-H...N [N...N = 3.016 (5) A, H...N = 2.15 A and N-H...N = 169 degrees] hydrogen bonds. The ribbons are further linked via weak C-H...O and C-H...N hydrogen bonds. In adjacent planes, anions lie opposite cations; pi-pi interactions (separation a/2 = 3.520 A) exist between the anions and the cations, and stacks are formed, running along the a axis. The cations are disordered over two interpenetrating sites, with occupancies of 0.833 (5) and 0.167 (5).

Potassium 3-cyano-4-(dicyanomethylene)-5-oxo-4,5-dihydro-1H-pyrrol-2-olate.

The crystal structure of the title potassium salt, K(+).C(8)HN(4)O(2)(-), of the organic anion 3-cyano-4-(dicyanomethylene)-5-oxo-4,5-dihydro-1H-pyrrol-2-olate shows that the dicyanomethylene moiety is able to accept an electron in the same way as does tetracyanoethylene, to yield the novel product. The organic anion is nearly planar, with deviations caused by steric crowding among the exocyclic cyano groups. The K(+) cations lie within tricapped trigonal prisms that stack to form channels. The three-dimensional structure is completed by the formation of hydrogen-bonded chains by the anions.

Crystal structure of the inclusion complex of beta-cyclodextrin with mefenamic acid from high-resolution synchrotron powder-diffraction data in combination with molecular-mechanics calculations.

The crystal structure of the inclusion complex of beta-cyclo-dextrin with mefenamic acid has been determined from a combination of high-resolution synchrotron powder-diffraction data and molecular-mechanics calculations. A grid search indicates two possible solutions, which are corroborated by molecular-mechanics calculations, while Rietveld-refinement results suggest the crystal structure that is more likely to be formed in the solid state. Mefenamic acid is partially included in beta-cyclodextrin with either the xylyl or the benzoic-acid moiety being inside its cavity. In both solutions mefenamic acid and beta-cyclodextrin form a monomeric complex in a herringbone packing scheme.