Crystal Packing Arrangement Research Articles

Decisive interactions between the heterocyclic moiety and the cluster observed in polyoxometalate-surfactant hybrid crystals.

Inorganic-organic hybrid crystals were successfully obtained as single crystals by using polyoxotungstate anion and cationic dodecylpyridazinium (C12pda) and dodecylpyridinium (C12py) surfactants. The decatungstate (W10) anion was used as the inorganic component, and the crystal structures were compared. In the crystal comprising C12pda (C12pda-W10), the heterocyclic moiety directly interacted with W10, which contributed to a build-up of the crystal structure. On the other hand, the crystal consisting of C12py (C12py-W10) had similar crystal packing and molecular arrangement to those in the W10 crystal hybridized with other pyridinium surfactants. These results indicate the significance of the heterocyclic moiety of the surfactant to construct hybrid crystals with polyoxometalate anions.

Working out how to pack benzene in silico

Theoretical Chemistry Many organic compounds crystallize in several different energetically similar packing arrangements, or polymorphs. This complicates processes such as drug formulation that rely on reproducible crystallization. Yang et al. have now achieved the long-standing goal of calculating a crystal packing arrangement from first principles to an accuracy that can distinguish polymorphs (see the Perspective by Price). They used benzene as a prototypical test case and applied quantum chemical methods that improve estimates of multibody interactions. The results bode well for future applications of theory to optimization of crystallization protocols. Science , this issue p. [640][1]; see also p. [619][2] [1]: /lookup/doi/10.1126/science.1254419 [2]: /lookup/doi/10.1126/science.1257250

Theoretical chemistry. Ab initio determination of the crystalline benzene lattice energy to sub-kilojoule/mole accuracy.

Computation of lattice energies to an accuracy sufficient to distinguish polymorphs is a fundamental bottleneck in crystal structure prediction. For the lattice energy of the prototypical benzene crystal, we combined the quantum chemical advances of the last decade to attain sub-kilojoule per mole accuracy, an order-of-magnitude improvement in certainty over prior calculations that necessitates revision of the experimental extrapolation to 0 kelvin. Our computations reveal the nature of binding by improving on previously inaccessible or inaccurate multibody and many-electron contributions and provide revised estimates of the effects of temperature, vibrations, and relaxation. Our demonstration raises prospects for definitive first-principles resolution of competing polymorphs in molecular crystal structure prediction.

Solvate-dependent spin crossover and exchange in cobalt(II) oxazolidine nitroxide chelates.

Two oxazolidine nitroxide complexes of cobalt(II), [Co(II)(L(•))2](B(C6F5)4)2·CH2Cl2 (1) and [Co(II)(L(•))2](B(C6F5)4)2·2Et2O (2), where, L(•) is the tridentate chelator 4,4-dimethyl-2,2-bis(2-pyridyl)oxazolidine N-oxide, have been investigated by crystallographic, magnetic, reflectivity, and theoretical (DFT) methods. This work follows on from a related study on [Co(II)(L(•))2](NO3)2 (3), a multifunctional complex that simultaneously displays magnetic exchange, spin crossover, and single molecule magnetic features. Changing the anion and the nature of solvation in the present crystalline species leads to significant differences, not only between 1 and 2 but also in comparison to 3. Structural data at 123 and 273 K, in combination with magnetic data, show that at lower temperatures 1 displays low-spin Co(II)-to-radical exchange with differences in fitted J values in comparison to DFT (broken symmetry) calculated J values ascribed to the sensitive influence of a tilt angle (θ) formed between the Co(dz(2)) and the trans-oriented O atoms of the NO radical moieties in L(•). Spin crossover in 1 is evident at higher temperatures, probably influenced by the solvate molecules and crystal packing arrangement. Complex 2 remains in the high-spin Co(II) state between 2 and 350 K and undergoes antiferromagnetic exchange between Co-radical and radical-radical centers, but it is difficult to quantify. Calculations of the magnetic orbitals, eigenvalue plots, and the spin densities at the Co and radical sites in 1 and 2 have yielded satisfying details on the mechanism of metal-radical and radical-radical exchange, the radical spins being in π*NO orbitals.

Linking crystal structure with temperature-sensitive vibrational modes in calcium carbonate minerals.

We demonstrate a correlation between how an IR-active vibrational mode responds to temperature changes and how it responds to crystallinity differences. Infrared (IR) spectroscopy was used to track changes in carbonate-related vibrational modes in three different CaCO3 polymorphs (calcite, aragonite, and vaterite) and CaMg(CO3)2 (dolomite) during heating. Of the three characteristic IR-active carbonate modes, the in-plane bending mode (ν4) shows the most pronounced changes with heating in polymorphs that have planar carbonate arrangements (calcite, aragonite, and dolomite). In contrast, this mode is virtually unchanged in vaterite, which has a canted arrangement of carbonate units. We correlate these trends with recent studies that identified the ν4 mode as most susceptible to changes related to crystallinity differences in calcite and amorphous calcium carbonate. Thus, our results suggest that studies of packing arrangements could provide a generalizable approach to identify the most diagnostic vibrational modes for tracking either temperature-dependent or crystallinity-related effects in IR-active solids.

Crystallographic analysis of an RNA polymerase σ-subunit fragment complexed with -10 promoter element ssDNA: quadruplex formation as a possible tool for engineering crystal contacts in protein-ssDNA complexes.

Structural studies of -10 promoter element recognition by domain 2 of the RNA polymerase σ subunit [Feklistov & Darst (2011), Cell, 147, 1257-1269] reveal an unusual crystal-packing arrangement dominated by G-quartets. The 3'-terminal GGG motif of the oligonucleotide used in crystallization participates in G-quadruplex formation with GGG motifs from symmetry-related complexes. Stacking between neighboring G-quadruplexes results in the formation of pseudo-continuous four-stranded columns running throughout the length of the crystal (G-columns). Here, a new crystal form is presented with a different arrangement of G-columns and it is proposed that the fortuitous finding of G-quartet packing could be useful in engineering crystal contacts in protein-ssDNA complexes.

Putative dioxygen-binding sites and recognition of tigecycline and minocycline in the tetracycline-degrading monooxygenase TetX

Expression of the aromatic hydroxylase TetX under aerobic conditions confers bacterial resistance against tetracycline antibiotics. Hydroxylation inactivates and degrades tetracyclines, preventing inhibition of the prokaryotic ribosome. X-ray crystal structure analyses of TetX in complex with the second-generation and third-generation tetracyclines minocycline and tigecycline at 2.18 and 2.30 Å resolution, respectively, explain why both clinically potent antibiotics are suitable substrates. Both tetracyclines bind in a large tunnel-shaped active site in close contact to the cofactor FAD, pre-oriented for regioselective hydroxylation to 11a-hydroxytetracyclines. The characteristic bulky 9-tert-butylglycylamido substituent of tigecycline is solvent-exposed and does not interfere with TetX binding. In the TetX-minocycline complex a second binding site for a minocycline dimer is observed close to the active-site entrance. The pocket is formed by the crystal packing arrangement on the surface of two neighbouring TetX monomers. Crystal structure analysis at 2.73 Å resolution of xenon-pressurized TetX identified two adjacent Xe-binding sites. These putative dioxygen-binding cavities are located in the substrate-binding domain next to the active site. Molecular-dynamics simulations were performed in order to characterize dioxygen-diffusion pathways to FADH2 at the active site.

A Metallosupramolecular Octahedron Assembled from Twelve Copper(I) Metal Ions and Six 4,4′‐(1,2‐Phenylene)bis(3,5‐dimethylpyrazol‐1‐ide) Ligands

AbstractThe novel coordination compound [CuI12(C16H16N4)6]·8DMAc, (2), (DMAc = N, N‐dimethylacetamide) was prepared in solvothermal or microwave assisted reaction. It contains four metallamacrocyclic trinuclear copper(I) pyrazolate coordination units, which occupy four (opposite) faces of an imaginary metallosupramolecular octahedron. Six (4,4′‐(1,2‐phenylene)bis(3,5‐dimethylpyrazol‐1‐ide) ligands (L12–) are placed at the corners of the octahedron. Crystals of the free ligand H2L1 [1,2‐bis(3,5‐dimethyl‐1H‐pyrazol‐4‐yl)benzene, (1)], and [CuI12(C16H16N4)6]·8DMAc (2), were characterized by single‐crystal X‐ray structure analyses. Lingand 1 crystallizes in the monoclinic crystal system, with: a = 9.0118(9), b = 14.0075(11), c = 11.7484(11) Å, β = 104.945(5)°, V = 1432.9(2) Å3, space group P21/c (no. 14). Compound 2 crystallizes in the tetragonal system, with: a = b = 19.506(5), c = 42.888(5) Å, V = 16318(6) Å3, space group I41/amd (no. 141). Compound 2 represents a porous structure, where each metallosupramolecular octahedron encloses a solvent‐filled cavity of 889 Å3 (accounting for 6 DMAc molecules, 21.8 % of the cell volume). The incomplete crystal packing arrangement of adjacent [CuI12(C16H16N4)6] moieties in addition leads to solvent‐filled interstitial voids accounting to 8.1 % of the cell volume. Removing solvent molecules in vacuo is accompanied by reversible structural changes, leading to a partial loss of porosity, as revealed by Ar‐BET sorption analysis. Compounds 1 and 2 were further characterized by elemental and thermogravimetric analysis, X‐ray powder diffraction, FTIR‐, UV/Vis‐ and fluorescence spectroscopy. Preliminary results on the activation of molecular oxygen by compound 2 are presented.

Influence of Anions and Alkyl Chain Lengths ofN-Alkyl-n-(R)-12-Hydroxyoctadecyl Ammonium Salts on Their Hydrogels and Organogels

The self-assembly and gelating characteristics of a set of N-alkyl-(R)-12-hydroxyoctadecylammonium salts (n-HOA-X, where n = 0-6, 18 is the length of the alkyl chain on nitrogen, X = Cl, n = 3, and X = Br, NO3, and BF4) are described. Solid-solid phase transitions were observed for powders of n-HOA-Cl, and orthorhombic-type crystal packing arrangements and lattice spacings were calculated from X-ray diffractograms at 22 °C. The diffractogram of 3-HOA-Br indicates the presence of more than one morph at room temperature, and that of 3-HOA-I corresponds to a lamellar packing arrangement. Differences in the molecular packing arrangements of 3-HOA-X are reflected in their gelation abilities. The melting temperatures (T(gel)) of the hydrogels of 3-HOA-Br are higher than those of 3-HOA-Cl at the same concentrations, and 3-HOA-I failed to gelate any of the investigated liquids. 3-HOA-NO3 gelated only water and CCl4 and 3-HOA-BF4 formed only hydrogels. Plots of changes in conductivities of the 3-HOA-X salts (where X = Cl, Br, NO3 and BF4) as a function of temperature were used to calculate the critical aggregation concentrations (CGCs). Because the CGCs from the 'falling drop' method are nearly the same as those from the conductivity measurements, aggregation, nucleation, and gelation must occur within a very narrow 3-HOA-X concentration range. T(gel) values of 2 wt % 3-HOA-Cl hydrogels (prepared by fast cooling of the sol phase) increased upon adding KCl up to 0.1 M. The effects can be attributed principally to the chloride anion rather than its cation partners. The properties of the hydrogels of 3-HOA-X do not follow the Hofmeister ranking rule. The variations in the counterions afford detailed insight into the behavior of 3-HOA-X in their neat solids and assemblies in gels as well as the processes accompanying gel formation in water and organic liquids.

A water wire inL-prolyl-L-serine monohydrate

Despite the extra functional group in the serine side chain, the crystal packing arrangement of the title compound {systematic name: (S)-3-hydroxy-2-[(S)-pyrrolidine-2-carboxamido]propanoic acid monohydrate}, C8H14N2O4·H2O, is essentially the same as observed for a series of L-Pro-L-Nop peptide hydrates, where Nop is a strictly nonpolar residue. This is rendered possible by a monoclinic P2(1) packing arrangement with Z' = 2 that deviates from orthorhombic P2(1)2(1)2(1) symmetry only for the seryl hydroxy groups, which form infinite O-H···O-H hydrogen-bonded chains along the 5.3 Å a axis. At the same time, cocrystallized water molecules form parallel water wires.

Water soluble pentacene

A water soluble pentacene, potassium 3,3′-(pentacene-6,13-diylbis(sulfanediyl))dipropanoate (4), has been synthesized and characterized. The synthesis of 4 is straightforward and scalable, and its isolation does not require time consuming chromatographic separations. UV-vis spectra in several solvents indicate an optical HOMO–LUMO gap of approximately 1.91–1.97 eV. Water soluble pentacene 4 is long-lived in the solution phase and in the solid state. Because it forms stable solutions, inks based on 4 have been formulated and printed onto paper and flexible plastic using an unmodified commercial ink-jet printer. A bi-layer photovoltaic cell using 4 as donor and [60]fullerene as acceptor was fabricated and shown to be active. The crystal structure of the pentacene diacid precursor to water soluble pentacene 4 has been solved and shows a parallel displaced arrangement of pentacene rings, indicative of stabilizing π–π stacking interactions. DFT modeling for 4, however, suggests an unusual, low energy conformation in which both potassium carboxylate moieties are located on the same face (syn) of the pentacene π system. Likewise, calculated two-molecule stacks of 4 suggest a crystal packing arrangement in which potassium carboxylate moieties are intercalated between adjacent pentacene rings.

Insights of Dosage form Design: Polymorphs and Cocrystals

Formulators are charged with the responsibility to formulate a bioequivalent product (in case of ANDA) product which is physically and chemically stable, manufacturable at commercial scale. Different crystal structures in polymorphs arise when the drug substance crystallizes in different crystal packing arrangements and/or different conformations. Besides, Polymorphs cocrystallization is now important method to achieve crystalline forms of molecules where alternative polymorphs or salts or solvates are desired. Regulatory road map for polymorphs approval is quite clear and for cocrystals draft guidance is on scientific advisory form public. From Intellectual property perspectives polymorphs and cocrystal patents are approved in different countries within the meaning specified in the act. Overall the patentability of polymorphs and cocrystals directly affects the business driven strategy for research based Pharmaceuticals as well as collaborative research universities for science updation for better health care.

Influence of the Hydroxyl Position in Racemic Hydroxyoctadecanoic Acids on the Crystallization Kinetics and Activation Energies of Gels and Dispersions in Mineral Oil

Minor changes in molecular structure affect the ability of racemic hydroxyoctadecanoic acids (nHSA, where n is the position of the hydroxyl group) to form molecular gels in a low polarity liquid, mineral oil, and influence their supramolecular structures. The activation energy and energy released during crystallization of 2HSA and 3HSA from solutions or sols are significantly lower than those of 6HSA, 8HSA, 10HSA, 12HSA, and 14HSA. The lower activation energies are associated with the ease of molecules of 2HSA or 3HSA to add to a face of a growing crystal lattice or the ease in which the critical nuclei are reached; the change in the activation energies appears to be related, in part, to the critical size of the crystallites, which, in turn, depends on the energy associated with the creation of the new phase and the interfacial free energy of the nucleated species with the liquid component. When the polar groups are close in proximity, the crystal packing arrangements are able to sequester these groups aw...

Survey of conformational isomerism in (E)-2-[(4-bromophenylimino)methyl]-5-(diethylamino)phenol compound from structural and thermochemical points of view

In this study, (E)-2-[(4-bromophenylimino)methyl]-5-(diethylamino)phenol compound was investigated by mainly focusing on conformational isomerism. For this purpose, molecular structure and spectroscopic properties of the compound were experimentally characterized by X-ray diffraction, FT-IR and UV–Vis spectroscopic techniques, and computationally by DFT method. The X-ray diffraction analysis of the compound shows the formation of two conformers (anti and eclipsed) related to the ethyl groups of the compound. The two conformers are connected to each other by non-covalent C–H⋯Br and C–H⋯π interactions. The combination of these interactions is resulted in fused R22(10) and R24(20) synthons which are responsible for the tape structure of crystal packing arrangement. The X-ray diffraction and FT-IR analyses also reveal the existence of enol form in the solid state. From thermochemical point of view, the computational investigation of isomerism includes three studies: the calculation of (a) the rate constants for transmission from anti or eclipsed conformations to transition state by using Eyring equation, (b) the activation energy needed for isomerism by using Arrhenius equation, (c) the equilibrium constant from anti conformer to eclipsed conformer by using the equation including the change in Gibbs free energy. The dependence of tautomerism on solvent types was studied on the basis of UV–Vis spectra recorded in different organic solvents. The results showed that the compound exists in enol form in all solvents except ethyl alcohol.

Structure of the tetradecanucleotide d(CCCCGGTACCGGGG)2 as an A-DNA duplex.

The crystal structure of the tetradecanucleotide sequence d(CCCCGGTACCGGGG)(2) has been determined at 2.5 Å resolution in the tetragonal space group P4(1). This sequence was designed with the expectation of a four-way junction. However, the sequence crystallized as an A-DNA duplex and represents more than one full turn of the A-helix. The crystallographic asymmetric unit consists of one tetradecanucleotide duplex. The structural parameters of the A-type DNA duplex structure and the crystal-packing arrangement are described. One Mn(2+) ion was identified with direct coordination to the N7 position of G(13) and a water molecule at the major-groove side of the C(2)·G(13) base pair.

Probing CH-π(alkyne) interactions in a series of ethynylferrocenes

A neoteric correlation between the cyclopentadienyl (Cp)-aryl dihedral angle and crystal packing arrangement is confirmed in the structural determination of three ethynylferrocene substituted naphthalenes. Two of the naphthalenes have approximately orthogonal Cp and aryl ring systems and feature an inversion dimer motif with CH⋯π(alkyne) short contacts. This motif is found in other arylethynylferrocenes. DFT calculations suggest the difference in energy between different dihedral conformations is of the same order as a weak hydrogen bond. Focussing on weak hydrogen bonds that involve the ethynyl group, other comparisons are made with a new polymorph of diferrocenylbutadiyne and the trans-isomer of 1,4-diferrocenylbut-1-ene-3-yne. Although the intermolecular forces described for the subject ethynylferrocenes are weak, they nonetheless give rise to distinctive structural motifs that may be exploitable in future supramolecular design.

Design of Clathrate Compounds that Use Only Weak Intermolecular Attractions

Intermolecular attractive forces that are considerably weaker than hydrogen bonding and coordination complexation may be used in the design of new molecules that function as host molecules in the solid-state. Known literature examples of accidentally discovered hosts (clathrands), which do not involve strong interactions in their crystals, are identified and discussed. Their molecular symmetry and supramolecular interactions are analysed in order to identify structural features that facilitate and promote molecular inclusion. The solid-state properties of a family of designed compounds that embody these principles are then described. Prediction of their inclusion behaviour was 95 % successful and a wide variety of crystal packing arrangements were encountered. This is an inevitable consequence of competition between many different molecular interactions of comparable energy during the crystallisation process. The lowest energy combination of these host–host and host–guest associations generates the observed outcome. One consequence of this behaviour is that detailed prediction of a new clathrate crystal packing arrangement is extremely difficult. However, a second consequence is that crystal structure analysis provides a rich source of information about weak intermolecular forces and new supramolecular synthons that previously had remained hidden.

XPac dissimilarity parameters as quantitative descriptors of isostructurality: the case of fourteen 4,5′-substituted benzenesulfonamido-2-pyridines obtained by substituent interchange involving CF3/I/Br/Cl/F/Me/H

Crystal structures of fourteen 4,5′-substituted benzenesulfonamido-2-pyridines, with tautomeric forms R1–C6H4–SO2–NC5NH4–R2 or R1–C6H4–SO2–NH–C5NH3–R2, and with R1 = CF3, I, Br, Cl, Me, F, H and R2 = CF3 or I are reported. Comparisons carried out with the program XPac show that all investigated structures display a common 3D arrangement of N–H⋯N bonded centrosymmetric dimers. This isostructural series is exceptional in its completeness and in the diversity of the substituents involved. Accordingly, the XPac dissimilarity index x, a measure of how far two structures deviate from perfect geometrical similarity, varies from 0.9 for the interchange R1 = Br → Cl to 9.5 for the simultaneous interchange of R1 = I → H and R2 = CF3 → I. XPac plots of individual dissimilarity parameters have been used to elucidate details of geometrical similarities and differences between structures. This indicated that the geometry is preserved most closely within bc-layers that are composed of 1D slipped stacks of N–H⋯N bonded dimers, with interlayer van der Waals interactions being dominated by R1⋯R2 contacts. The main mode of geometrical adjustment for the size of R1 is a parallel shift of neighbouring layers against one another in the direction perpendicular to the layer plane, whilst the relative orientations of molecules within each layer are altered to a much smaller extent, even for those structure pairs representing R1 substituents that are very different in size. This study shows that the ability of two compounds to crystallise in fundamentally the same crystal structure depends not only on how much their molecules differ in shape but also, critically, on the specific tolerance characteristics of the crystal packing arrangement concerned. As a comparison with the present study, dissimilarity indices are reported for a set of 24 isostructural 4,4′-substituted benzenesulfonamidobenzenes previously subjected to XPac analysis.

Crystal and molecular structures of 2-(4-chlorophenyl)-5,7-dimethoxyquinolin-4-yl phenyl bis(2-chloroethyl) phosphoramidate

2-(4-Chlorophenyl)-5,7-dimethoxyquinolin-4-yl phenyl bis(2-chloroethyl)phosphoramidate is synthesized and characterized by NMR, IR and single crystal X-ray crystallography. The crystal is triclinic, \(P\bar 1\) space group, with a = 9.5188(19) A, b = 12.856(3) A, c = 13.250(3) A, V = 1412.0(5) A)3, and Z = 2 (at 291(2) K). The crystal packing arrangement indicates that the molecule is stacked through π...π aromatic stacking interactions.

Intermolecular CH⋯O hydrogen bonds in formyl-substituted diphenylhexatriene, a [2+2] photoreactive organic solid: Crystal structure and IR, NMR spectroscopic evidence

(E,E,E)-1,6-di(4-formylphenyl)-1,3,5-hexatriene (1) undergoes [2 + 2] photocycloaddition in the solid state, while the unsubstituted parent, (E,E,E)-1,6-diphenyl-1,3,5-hexatriene (DPH), is photochemically inert as we reported previously. Although the steering effect of the formyl group for the photoreaction is very clear, the crystal structure of 1 had been unknown. In this study, single crystals of 1 suitable for X-ray diffraction (XRD) analysis were prepared and the crystal structure was investigated. The molecules in crystal are linked through intermolecular CH⋯O-type hydrogen bonds involving formyl groups to form a 3D structure of π-stacked crystal packing arrangement with intermolecular distance of 3.926 Å (=b), less than the Schmidt’s criteria of 4.2 Å for the [2 + 2] photoreaction. The existence of CH⋯O hydrogen bonds is evidenced by FT-IR, 1H and 13C NMR spectroscopic measurements. For the IR peak assignments, ab initio and DFT calculations were performed. The solid-state 1H and 13C NMR spectra were measured using the CRAMPS and CP/MAS techniques, respectively. Owing to the small CH⋯O angular dependence of the interaction energy (directionality), the CH⋯O hydrogen bonds are formed in a multiple manner. Thus, although being rather weak, these hydrogen bonds play a decisive role in constructing the [2 + 2] photoreactive crystal structure, without any other stronger intermolecular interactions coexisting.