Symmetry-independent Molecules Research Articles

Solid-state transformations in the β-form of chlorpropamide on cooling to 100 K

A single-crystal X-ray diffraction study of the effect of cooling down to 100 K on the β-form of chlorpropamide, 4-chloro-N-(propylaminocarbonyl)benzenesulfonamide, has revealed reversible phase transitions at ∼257 K and between 150 and 125 K: β (Pbcn, Z' = 1) ⇔ β(II) (P2/c, Z' = 2) ⇔ β(III) (P2/n, a' = 2a, Z' = 4); the sequence corresponds to cooling. Despite changes in the space group and number of symmetry-independent molecules, the volume per molecule changes continuously in the temperature range 100-300 K. The phase transition at ∼257 K is accompanied by non-merohedral twinning, which is preserved on further cooling and through the second phase transition, but the original single crystal does not crack. DSC (differential scanning calorimetry) and X-ray powder diffraction investigations confirm the phase transitions. Twinning disappears on heating as the reverse transformations take place. The second phase transition is related to a change in conformation of the alkyl tail from trans to gauche in 1/4 of the molecules, regularly distributed in the space. Possible reasons for the increase in Z' upon cooling are discussed in comparison to other reported examples of processes (crystallization, phase transitions) in which organic crystals with Z' > 1 have been formed. Implications for pharmaceutical applications are discussed.

2-(4-Phenyl-5-pyridin-2-yl-4H-1,2,4-triazol-3-yl)cyclohexanecarboxylic Acid and Its DMSO Solvate: Synthesis, Crystal Structure and Biological Activity

A new 1,2,4-triazole derivative, 2-(4-phenyl-5-pyridin-2-yl-4H-1,2,4-triazol-3-yl)cyclohexanecarboxylic acid, C20H20N4O2 (I), and its dimethyl sulfoxide solvate 1:1 (II) have been synthesized and their crystal structure was established. Compound (I) was screened for its antiproliferative and antiinflammatory activity. Structural analysis indicated the substantial difference between two symmetry independent molecules in (I) and this in (II), it manifests in the relative orientation of pyridine/phenyl and triazole rings, as well as in the orientation of carboxyl group with respect to cyclohexane ring. The molecules A and B in the crystal (I) form two hydrogen-bonded chains through O–Hcarboxyl and Ntriazole atoms, giving separate catemers of symmetry independent molecules. The catemer of (IA) running along the 21 axis is homochiral, while the catemer (IB) is racemic—formed about the c glide plane. In the crystalline solvate (II) complexation of (I) with DMSO induced enantiomeric self-resolution. Obtained crystals are racemic twins, in which each part is built of one enantiomer of (I) having the relative configuration 11S,12R or 11R,12S. A pair of host–guest molecules is linked by the O–Hcarboxyl⋯ODMSO hydrogen bond.

(1RS,6SR)-Ethyl 4-(2,4-dichlorophenyl)-6-(4-fluorophenyl)-2-oxocyclohex-3-ene-1-carboxylate

There are two symmetry-independent mol­ecules in the asymmetric unit of the title compound, C21H17Cl2FO3. Both these mol­ecules are very similar: the normal probability plots for bond lengths, angles and even for torsion angles show that the differences are of a statistical nature. A pseudocentre of symmetry is located between the symmetry-independent mol­ecules at [0.245 (1), 0.535 (19), 0.909 (1)]. The cyclo­hexene rings have slightly distorted sofa conformations in both mol­ecules and the two benzene rings are inclined by dihedral angles of 61.33 (14) and 62.85 (14)°. In the crystal, relatively short inter­molecular C—H⋯O inter­actions join mol­ecules into homomolecular (i.e. ⋯AAA⋯ and ⋯BBB⋯) chains along the b axis. These chains are inter­connected by further heteromolecular C—H⋯O inter­actions.

N-{4-[(E)-(4-Methylphenyl)iminomethyl]phenyl}acetamide

There are two symmetry-independent mol­ecules in the asymmetric unit of the title compound, C16H16N2O, that differ in conformation. The dihedral angles between the benzene rings in the two mol­ecules are 44.35 (19) and 48.14 (17)°, but the rings twist in opposite directions. The acetamide groups make nearly equal dihedral angles of 25.4 (3) and 25.7 (3)° with the parent benzene rings. An S(6) ring motif is formed in each mol­ecule by intra­molecular C—H⋯O close contacts. In the crystal, strong N—H⋯O hydrogen bonds between acetamide groups generate a C(4) chain motif arranging the mol­ecules into two symmetry-independent polymeric structures extending along [010].

Bis[3α,7α,12α-tris(4-nitrobenzoyloxy)-5β-cholan-24-yl] disulfide–ethyl acetate–n-hexane (4/4/1)

The crystal structure of the title compound, C90H100N6O24S2·C4H8O2·0.25C6H14, solved and refined against synchrotron diffraction data, contains two formula units in the asymmetric unit with the all-trans n-hexane mol­ecule having half-occupancy and one of the ethyl acetate mol­ecules disordered over two positions. The two symmetry-independent disulfide mol­ecules are assembled by approximate face-to-face and face-to-edge inter­actions between their 4-nitro­benzo­yloxy groups into an inter­twined dimer having a double-helix-type structure. The centrally placed disulfide bridges in the two symmetry-independent mol­ecules exhibit different helicity as shown by the C—S—S—C torsion angles of 71.0 (1) and −92.5 (1)°.

Symmetry breaking and light-induced spin-state trapping in a mononuclearFeIIcomplex with the two-step thermal conversion

Crystallographic, magnetic, and Raman investigations of the mononuclear $[{\text{Fe}}^{\text{II}}(\text{Hpy-DAPP})]{({\text{BF}}_{4})}_{2}$ complex are presented. Its particular feature is a two-step thermal spin conversion in spite of a unique symmetry-independent iron site per unit cell. The plateau around 140 K is associated with a symmetry breaking visible by the appearance of weak $(0k0)$ $k$ odd Bragg peaks. Symmetries of the high-temperature high-spin state and of the low-temperature low-spin state are both monoclinic $P{2}_{1}/c$, so that the symmetry breaking on the plateau is associated with a reentrant phase transition. It is discussed in relation with Ising-type microscopic models. At the plateau level, the two symmetry-independent molecules differ both by their spin state and the conformation (chair versus twist-boat) of one metallocycle. At low-temperature photoinduced phenomena have been investigated: a partial phototransformation [light-induced excited spin-state trapping (LIESST) effect] is observed under visible red irradiation. Raman spectroscopy shows that the molecular photoinduced state is the high-spin one. Nevertheless, as no macroscopic symmetry breaking is observed, the unique average cationic $[{\text{Fe}}^{\text{II}}(\text{Hpy-DAPP})]$ state of the unit cell is intermediate between pure low-spin and high-spin states and presents a conformational disorder for one metallocycle. Reverse-LIESST has also been evidenced using near infrared excitation. Thus, the mononuclear $[\text{Fe}(\text{Hpy-DAPP})]{({\text{BF}}_{4})}_{2}$ compound offers the opportunity to discuss the interplay between spin conversion, molecular conformational change, and ordering processes.

2-(4-Fluorophenyl)-5-iodo-3-isopropylsulfinyl-1-benzofuran

In the title compound, C17H14FIO2S, the 4-fluoro­phenyl ring makes a dihedral angle of 18.88 (9)° with the mean plane of the benzofuran ring. In the crystal, pairs of inter­molecular I⋯O contacts [3.153 (2) Å] link the mol­ecules into inversion dimers.

Structures of cyclic dipeptides: an X-ray and computational study of cis- and trans-cyclo(Pip-Phe), cyclo(Pro-Phe) and their N-methyl derivatives

The crystal structures of eight cyclodipeptides are determined, incorporating pipecolic acid or proline and phenylalanine or N-methyl phenylalanine. This set of structures allows the evaluation of the effects on molecular conformation and crystal packing of imino acid ring-size, relative configuration of the two amino acids, and N-methylation. In the non-methylated compounds, hydrogen-bonding interactions form one-dimensional motifs that dominate the packing arrangement. Three compounds have more than one symmetry-independent molecule in the asymmetric unit (Z' > 1), indicative of a broad and shallow molecular energy minimum. Density functional theory calculations reveal the interplay between inter- and intramolecular factors in the crystals. Only for the N-methylated compounds do simulations of the molecules in the isolated state succeed to reproduce the observed crystallographic conformations. Puckering of the diketopiperazine ring and the deviation from planarity of the amide bonds are not reproduced in the remaining compounds. Cluster in vacuo calculations with a central cyclodipeptide molecule surrounded by hydrogen-bound molecules establish that hydrogen bonding is of major importance but that other intermolecular interactions must also contribute substantially to the crystal structure. More advanced periodic calculations, incorporating the crystallographic environment to the full extent, are necessary to correctly describe all the conformational features of these cyclodipeptide crystals.

1,3,4-Triphenyl-7-trifluoromethyl-1H-pyrazolo[3,4-b]quinoline at 293 and 100 K

In the structure of the title compound, C(29)H(18)F(3)N(3), belonging to the space group P6(5) (or P6(1)), three symmetry-independent molecules are arranged in two chains, with two molecules alternating along the 3(2) axes, whereas the remaining molecule forms a chain along [0001] due to the 6(5) screw axis. The conformation of each of the molecules is stabilized by an intramolecular C-H...N hydrogen bond, with C...N distances in the range 2.964 (6)-3.069 (5) A at room temperature (293 K) and 2.943 (4)-3.084 (4) A at low temperature (100 K). One molecule has its -CF(3) group ordered even at 293 K, which can be explained only by considering its involvement in two weak intermolecular C-H...F interactions, with C...F distances in the range 3.084 (6)-3.302 (5) A at 293 K and 3.070 (3)-3.196 (3) A at 100 K, and also a C-F...N interaction, with a C...N distance of 3.823 (5) A at 293 K and 3.722 (4) A at 100 K. The trifluoromethyl groups in the two remaining molecules are disordered at 293 K, whereas at 100 K the continuous (dynamic) positional disorder of one of the -CF(3) groups (of the molecule forming the chain along [0001]) is totally eliminated while the -CF(3) group disorder remains for the third molecule.

New Solid State Forms of the Anti-HIV Drug Efavirenz. Conformational Flexibility and HighZ′Issues

Structural information on the solid forms of efavirenz, a non-nucleoside reverse transcriptase inhibitor, is limited, although various polymorphic forms of this drug have been patented. We report here structural studies of four new crystal forms—a pure form, a cyclohexane solvate, and cocrystals with 1,4-cyclohexanedione and 4,4′-bipyridine. Temperature dependent single-crystal to single-crystal phase transitions are observed for the pure form and for the cyclohexane solvate with an increase in the number of symmetry independent molecules, Z′, upon a lowering of temperature. Other issues related to these solid forms, such as thermal stability, conformational flexibility, and high Z′ occurrences, are addressed by using a combined experimental and computational approach.

Ethenzamide–gentisic acid–acetic acid (2/1/1)

In the title co-crystal solvate, 2-ethoxy­benzamide–2,5-dihydroxy­benzoic acid–ethanoic acid (2/1/1), 2C9H11NO2·C7H6O4·C2H4O2, two nonsteroidal anti-inflammatory drugs, ethenzamide (systematic name: 2-ethoxy­benzamide) and gentisic acid (systematic name: 2,5-dihydroxy­benzoic acid), together with acetic acid (systematic name: ethanoic acid) form a four-component mol­ecular assembly held together by N—H⋯O and O—H⋯O hydrogen bonds. This assembly features two symmetry-independent mol­ecules of ethenzamide, forming supra­molecular acid–amide heterosynthons with gentisic acid and acetic acid. These heterosynthons involve quite strong O—H⋯O [O⋯O = 2.5446 (15) and 2.5327 (15) Å] and less strong N—H⋯O [N⋯O = 2.9550 (17) and 2.9542 (17) Å] hydrogen bonds. The overall crystal packing features several C—H⋯O and π–π stacking inter­actions [centroid–centroid distance = 3.7792 (11) Å].

Polymorphism in Isomeric Dihydroxybenzoic Acids

Multifunctional molecules are capable of assembling via different supramolecular synthons, or hydrogen bond motifs, between the same or different functional groups, leading to the possibility of polymorphism. We have employed sublimation and melt crystallization to generate two new crystalline polymorphs of 3,5-dihydroxybenzoic acid (DHBA), and a second form for 2,3-dihydroxybenzoic acid and 3,4-dihydroxybenzoic acid each. Since hydroxybenzoic acids tend to give solvate/hydrate crystal structures by solution crystallization, solvent-free methods are necessary to obtain single crystals of unsolvated forms. In addition to guest-free polymorphs, a new hydrate polymorph of 3,4-dihydroxybenzoic acid was crystallized from cold water. Polymorphs of dihydroxybenzoic acids differ in the number of symmetry-independent molecules (Z′), the nature of the hydrogen bond synthon, the molecular packing, and the unit cell parameters. Structural and thermal characterization of polymorphic phases shows that the commercial ma...

Hydrate of 2,3:4,5-di-O-isopropylidene-β-D-arabino-hexos-2-ulo-2,6-pyranose as new crystalline reagent in the preparation of Amadori derived peptides

Abstract We established, that crystalline hydrate of 2,3:4,5-di-O-isopropylidene-β-D-arabino-hexos-2-ulo-2,6-pyranose is a new, convenient and stable reagent for solid phase synthesis of peptide derived Amadori products. The structure of the title compound was studied by X-ray analysis, NMR spectroscopy, and high resolution ESI-MS. The crystal structure indicated the existence of two symmetry-independent molecules that were not connected with hydrogen bonds. A comparison with previously reported 2,3:4,5-di-O-isopropylidene-β-D-fructopyranose revealed, that these two compounds are isostructural.

Cis-N-(2-Hydroxycyclohexyl)-p-toluenesulfonamide

There are two symmetry-independent mol­ecules in the asymmetric unit of the title compound, C13H19NO3S. The cyclo­hexane rings in the two mol­ecules adopt chair configurations. The hydr­oxy and amino groups on the cyclo­hexane ring assume axial and equatorial orientations, respectively, with respect to the plane of the ring. The crystal structure is stabilized by two inter­molecular N—H⋯O and O—H⋯O hydrogen bonds from the two symmetry-independent mol­ecules.

5-Fluoro-2-methyl-3-phenylsulfonyl-1-benzofuran

There are two symmetry-independent mol­ecules, A and B, in the asymmetric unit of the title compound, C15H11FO3S. The crystal studied was an inversion twin with a 0.21 (12):0.79 (12) domain ratio. In the crystal structure, the two independent mol­ecules are related by a pseudo-inversion center. The dihedral angles formed by the phenyl ring and the plane of the benzofuran fragment are 80.2 (1)° in mol­ecule A and 80.7 (1)° in mol­ecule B. In the crystal structure, the A and B mol­ecules are linked by aromatic π–π inter­actions between the furan and benzene rings of neighbouring benzofuran systems; the centroid–centroid distances are 3.671 (7) and 3.715 (7) Å. In addition, the crystal structure also exhibits two weak non-classical inter­molecular C—H⋯O hydrogen bonds.

Bis(N-triisopropylsilylquinolin-8-aminato)nickel(II)

The reddish-brown title complex, [Ni(C18H27N2Si)2], was prepared via the salt-metathesis reaction of N-triisopropyl­silyl-8-amido­quinoline lithium with nickelocene (NiCp2). The asymmetric unit contains two symmetry-independent mol­ecules with the Ni atoms in distorted tetra­hedral environments.

Diethyl 2-oxo-3-(2-oxo-2,3-dihydro-1H-indol-3-yl-idene)butane-dioate.

The title compound, C16H15NO6, crystallizes with two symmetry–independent mol­ecules in the asymmetric unit. The crystal structure is stabilized by inter­molecular C—H⋯O and N—H⋯O hydrogen bonds, and intra­molecular C—H⋯O hydrogen bonds. In addition, the crystal structure exhibits two inter­molecular C—H⋯π inter­actions.

Two two-dimensional hydrogen-bonded coordination networks: bis(3-carboxybenzoato-κO)bis(4-methyl-1H-imidazole-κN3)copper(II) and bis(3-methylbenzoato-κN)bis(4-methyl-1H-imidazole-κN3)copper(II) monohydrate

The title two-dimensional hydrogen-bonded coordination compounds, [Cu(C(8)H(5)O(4))(2)(C(4)H(6)N(2))(2)], (I), and [Cu(C(8)H(7)O(2))(2)(C(4)H(6)N(2))(2)].H(2)O, (II), have been synthesized and structurally characterized. The molecule of complex (I) lies across an inversion centre, and the Cu(2+) ion is coordinated by two N atoms from two 4-methyl-1H-imidazole (4-MeIM) molecules and two O atoms from two 3-carboxybenzoate (HBDC(-)) anions in a square-planar geometry. Adjacent molecules are linked through intermolecular N-H...O and O-H...O hydrogen bonds into a two-dimensional sheet with (4,4) topology. In the asymmetric part of the unit cell of (II) there are two symmetry-independent molecules, in which each Cu(2+) ion is also coordinated by two N atoms from two 4-MeIM molecules and two O atoms from two 3-methylbenzoate (3-MeBC(-)) anions in a square-planar coordination. Two neutral complex molecules are held together via N-H...O(carboxylate) hydrogen bonds to generate a dimeric pair, which is further linked via discrete water molecules into a two-dimensional network with the Schläfli symbol (4(3))(2)(4(6),6(6),8(3)). In both compounds, as well as the strong intermolecular hydrogen bonds, pi-pi interactions also stabilize the crystal stacking.

Cover Picture: ZAAC ‐ Journal of Inorganic and General Chemistry 13‐14/2009

AbstractThe cover picture shows a projection of the unit cell of the title compound [Fe(ppo)3] along the c axis. [Fe(ppo)3] crystallizes in the space group $R{\bar 3}$ with two symmetry independent molecules in the unit cell, A and B, situated on a three‐fold axis. In both symmetry independent molecules, the FeO6 units show distorted octahedral arrangement with a Fe–O(phenolato) bond length of 1.914(2) Å, which is shorter than the Fe–O(carbonyl) distance of 2.070(2) Å. In the unit cell, 12 FeO6 units, which alternate along the z axis, are involved in crystal packing of [Fe(ppo)3]. The crystal structure is mainly stabilized by C–H···π interactions between phenyl rings of the same layer and by C–H···O(phenolate) interactions between molecules from neighboring layers. More details are discussed in the article by M. Lalia‐Kantouri et al. on p. 2185ff.

Unmasking a third polymorph of a benchmark crystal-structure-prediction compound.

Unmasking a third polymorph of a benchmark crystal-structure-prediction compound.