A good-practice guide to solving and refining molecular organic crystal structures from laboratory powder X-ray diffraction data.

X -ray diffraction becomes a routine process these decades for determining crystal structure of the materials. Most of the crystal structures solved nowadays is based on single crystal X-ray diffraction because it solves the crystal and molecular structures from small molecules to macro molecules without much human intervention. However it is difficult to grow single crystals of sufficient size and quality for conventional single-crystal X-ray diffraction studies. In such cases it becomes essential that structural information can be determined from powder diffraction data. With the recent developments in the direct-space approaches for structure solution, ab initio crystal structure analysis of molecular solids can be accomplished from X-ray powder diffraction data. It should be recalled that crystal structure determination from laboratory X-ray powder diffraction data is a far more difficult task than that of its single-crystal counterpart, particularly when the molecule possesses considerable flexibility or there are multiple molecules in the asymmetric unit. Salicylic acid and its derivatives used as an anti-inflammatory drug are known for its numerous medicinal applications. In our study, we synthesized mononuclear copper (II) complex of salicylate derivative. The structural characterization of the prepared compound was carried out using powder X-ray diffraction studies. Crystal structure of the compound has been solved by direct-space approach and refined by a combination of Rietveld method using TOPAS Academic V4.1. Density Functional Theory (DFT) calculations have to be carried in the solid state for the compound using GaussianW9.0 in the frame work of a generalized-gradient approximation (GGA). The geometry optimization was to be performed using B3LYP density functional theory. The atomic coordinates were taken from the final X-ray refinement cycle.

Molecular surface structure of organic crystals observed by atomic force microscopy

Solving Molecular Crystal Structures from X-ray Powder Diffraction Data: The Challenges Posed by γ-Carbamazepine and Chlorothiazide N,N,-Dimethylformamide (1/2) Solvate

The crystal structures of 35 molecular compounds have been redetermined from laboratory monochromatic capillary transmission X-ray powder diffraction data using the simulated-annealing approach embodied within theDASHstructure solution package. The compounds represent industrially relevant areas (pharmaceuticals; metal coordination compounds; nonlinear optical materials; dyes) in which the research groups in this multi-centre study are active. The molecules were specifically selected to form a series within which the degree of structural complexity (i.e. degrees of freedom in the global optimization) increased systematically, the degrees of freedom increasing with increasing number of optimizable torsion angles in the structural model and with the inclusion of positional disorder or multiple fragments (counterions; crystallization solvent;Z′ > 1). At the lower end of the complexity scale, the structure was solved with excellent reproducibility and high accuracy. At the opposite end of the scale, the more complex search space offered a significant challenge to the global optimization procedure and it was demonstrated that the inclusion of modal torsional constraints, derived from the Cambridge Structural Database, offered significant benefits in terms of increasing the frequency of successful structure solution by restricting the magnitude of the search space in the global optimization.

The title compound [systematic name: 1-[(1R,2R,3S,4R)-2,3-dihydroxy-4-methyltetrahydrofuranyl]-5-fluoropyrimidine-2,4(1H,3H)-dione], C9H11FN2O5, is a prodrug of 5-fluorouracil used as a cytostatic in cancer therapy. Its crystal structure was determined from laboratory X-ray powder diffraction data. The compound crystallises in the triclinic space group P1 with two molecules in the asymmetric unit. These symmetrically independent molecules differ in their hydrogen-bond patterns, the pseudorotational angles P of their furanosyl fragments as well as their N-glycosidic torsion angles χ. The crystal structure of 5′-deoxy-5-fluorouridine, 1-[(1R,2R,3S,4R)-2,3-dihydroxy-4-methyltetrahydrofuranyl]-5-fluoropyrimidine-2,4(1H,3H)-dione], C9H11FN2O5, a prodrug of 5-fluorouracil used as a cytostatic in cancer therapy, was determined from laboratory X-ray powder diffraction data. The compound crystallises in the triclinic space group P1 with two symmetrically independent molecules differing in their hydrogen-bond patterns, the pseudorotational angles P of their furanosyl fragments as well as their N-glycosidic torsion angles χ.

The previously unreported crystal structure of (S)-Dapoxetine hydrochloride (DAPHCl), the only active pharmaceutical ingredient specially developed for the treatment of premature ejaculation in men, has been determined from laboratory X-ray powder diffraction data with DASH and refined by the Rietveld method with TOPAS-Academic. The structure was evaluated and optimized by dispersion-corrected DFT calculations. This compound crystallizes in an orthorhombic cell, space group P212121, with unit-cell parameters a= 6.3208(3) Å, b = 10.6681(5) Å, c = 28.1754(10) Å, V = 1899.89(14) Å3, Z = 4. The refinement converged to Rp= 0.0442, Rwp= 0.0577, and GoF = 2.440. The crystal structure is a complex 3D arrangement of DAPHCl moieties held together by hydrogen bonds, π⋯π, and C–H⋯π interactions. The chloride ions form layers parallel to the ab plane and are connected by dapoxetinium moieties through N–H⋯Cl and C–H⋯Cl hydrogen bonds. These layers stack along the c-axis, which are connected by C–H⋯π interactions. Hirshfeld surface analysis and fingerprint plot calculations have been performed.

Crystal structure from laboratory X-ray powder diffraction data, DFT-D calculations, Hirshfeld surface analysis, and energy frameworks of a new polymorph of 1-benzothiophene-2-carboxylic acid — ERRATUM - Volume 36 Issue 3

Knowledge of crystal structure is a prerequisite for understanding fundamental properties and developing applications of crystalline materials. Although single-crystal X-ray diffraction (XRD) is the most powerful experimental technique for determining crystal structures, the requirement for a single-crystal specimen can impose severe limitations on the scope of this technique. For materials that cannot be grown as suitable single crystals, structure determination must be tackled instead using powder XRD data. However, the task of carrying out structure determination from powder XRD data is significantly more challenging than from single-crystal XRD data, particularly for organic materials. As recently as the early 1990s, no organic molecular crystal structure had ever been solved directly from powder XRD data, as such materials present significant challenges for the application of traditional structure-solution techniques. However, since that time, the direct-space strategy for structure solution has transformed the field, such that structure determination of organic crystal structures of moderate complexity from powder XRD data is now relatively routine. This chapter gives an overview of the current opportunities for carrying out structure determination of organic materials directly from powder XRD data. Results from the application of the direct-space strategy are presented, with examples from several different fields within chemical, materials and biological sciences.

The general problem of the prediction of the crystal parameters and molecular structure of nonlinear molecules is taken up in a treatment that couples the molecular electronic structure determination to the surrounding crystalline lattice field. The molecular electronic structure method used may be at any level of sophistication, but we used the Hartree–Fock approximation in this application. A partial charge analysis of the molecular electronic structure is performed to establish the values of atom‐centered partial charges that interact via Coulomb's law, along with a Lennard–Jones potential between all atoms to establish a crystalline lattice field. The Lennard–Jones parameters are taken from the widely used AMBER force field. The lattice field terms are included in the molecular Hamiltonian and exert forces on the nuclei, leading to a somewhat different equilibrium structure than is obtained for the isolated molecule. The positions, orientations, and unit cell parameters are optimized for the lattice field, leading to a full determination of the crystal structure, including the space group. Results for sulfur dioxide, ammonia, and water are reported. In each case an equilibrium crystalline geometry faithfully reproducing the experimentally determined space group is obtained. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2003

Several benzothiophene-based compounds, including 1-benzothiophene-2-carboxylic acid, exhibit a wide variety of pharmacological activities. They have been extensively used to treat various types of diseases with high therapeutic effectiveness. In this contribution, the crystal structure of a new polymorph of 1-benzothiophene-2-carboxylic acid (BTCA) was determined from laboratory X-ray powder diffraction data with DASH, refined by the Rietveld method with TOPAS-Academic, and optimized using DFT-D calculations. The new form of 1-benzothiophene-2-carboxylic acid crystallizes in space group C2/c (No. 15) with a = 14.635(4), b = 5.8543(9), c = 19.347(3) Å, β = 103.95(1)°, V = 1608.8(6) Å3, and Z = 8. The structure is a complex 3D arrangement which can be described in terms of hydrogen-bonded dimers of BTCA molecules, joined by the acid–acid homosynthon, which interact through C–H⋯O hydrogen bonds to produce tapes further connected through head-to-tail π⋯π and edge-to-face C–H⋯π interactions. A comparison with a previously reported triclinic polymorph and with the related 1-benzofuran-2-carboxylic acid (BFCA) is also presented.

In 2010 we energy-minimized 225 high-quality single-crystal (SX) structures with dispersion-corrected density functional theory (DFT-D) to establish a quantitative benchmark. For the current paper, 215 organic crystal structures determined from X-ray powder diffraction (XRPD) data and published in an IUCr journal were energy-minimized with DFT-D and compared to the SX benchmark. The on average slightly less accurate atomic coordinates of XRPD structures do lead to systematically higher root mean square Cartesian displacement (RMSCD) values upon energy minimization than for SX structures, but the RMSCD value is still a good indicator for the detection of structures that deserve a closer look. The upper RMSCD limit for a correct structure must be increased from 0.25 Å for SX structures to 0.35 Å for XRPD structures; the grey area must be extended from 0.30 to 0.40 Å. Based on the energy minimizations, three structures are re-refined to give more precise atomic coordinates. For six structures our calculations provide the missing positions for the H atoms, for five structures they provide corrected positions for some H atoms. Seven crystal structures showed a minor error for a non-H atom. For five structures the energy minimizations suggest a higher space-group symmetry. For the 225 SX structures, the only deviations observed upon energy minimization were three minor H-atom related issues. Preferred orientation is the most important cause of problems. A preferred-orientation correction is the only correction where the experimental data are modified to fit the model. We conclude that molecular crystal structures determined from powder diffraction data that are published in IUCr journals are of high quality, with less than 4% containing an error in a non-H atom.

Molecular crystals, surfactant assemblies, and block copolymers are properly classified as “soft matter,” but these classes of materials are usually regarded as distinct owing to their different properties and applications. Furthermore, the length scales of translation order in typical molecular crystals are typically at least one order of magnitude smaller than in surfactant assemblies and block copolymers, which often organize as high symmetry hexagonal and cubic microstructures. Whereas the structures of molecular crystals are generally viewed to be governed by intermolecular forces at short length scales that impose local order, surfactant assemblies and block copolymers are locally disordered even though they form ordered microstructures at longer length scales. Though historically the crystal structures of most molecular crystals have been characterized for the purpose of understanding molecular structure, the recent emergence of crystal engineering as a solid-state discipline has shifted the focus toward the elucidation of the factors responsible for crystal packing and strategies for crystal design. This coincides with a growing interest in surfactants and block copolymers having materials properties that can be tuned precisely at the molecular level. As such, it seems opportune to begin examining the structural relationships that connect these classes of materials. The intent of this highlight is to provoke interest in such comparisons through examples of molecular crystals that exhibit features which mimic microstructures observed in surfactant assemblies and block copolymers. These compounds appear to be characterized by molecular components with some degree of amphiphilic character and supramolecular structural elements that (i) enforce topologies that are predestined to form certain high symmetry structures, (ii) introduce conformational softness that permits curvature at small length scales, (iii) form aggregates (i.e., through hydrogen bonding) which effectively increase the length scale so that curved surfaces required for high symmetry lattices can be formed with minimal energetic penalties. These examples suggest that the relationship between length scale, energy, curvature, and crystal symmetry bear further examination.

Predicting lattice energy and structure of molecular crystals by first-principles method: Role of dispersive interactions

Only two crystal structures of diorganotellurones have been reported to date, both of which contain cocrystallized solvents and one of which is stabilized by intramolecular Te-N secondary bonding interactions. This work describes the crystal structure of bis(2,6-diisopropylphenyl) tellurone, (C12H17)2TeO2 or C24H34O2Te, the first well-defined diorganotellurone without cocrystallized solvents and without stabilizing intramolecular contacts. The molecule has crystallographic twofold symmetry, with half the molecule as the asymmetric unit. The molecular structure is compared to previously reported tellurones and those computed at the density functional theory DFT/B3PW91 level. The molecules form two-dimensional layers as a result of a weak intermolecular hydrogen-bonding network. The layers are then stacked in an antiparallel manner to form the crystal packing structure. The Hirshfeld surface analysis was employed to visualize and quantify the intermolecular contacts in the molecular crystal structure, and the contribution of O...H and H...H interactions was found to be the dominating factor.

The crystal structures of 4-chloro-5-methyl-2-ammoniobenzenesulfonate and of the corresponding derivatives 4,5-dimethyl- and 4,5-dichloro-2-ammoniobenzenesulfonates have been determined from laboratory X-ray powder diffraction data. The tautomeric state of all three compounds could also be unequivocally determined from laboratory data, using careful Rietveld refinements. The tautomeric state was confirmed by IR spectroscopy. The compounds are neither isostructural to each other nor to the 5-chloro-4-methyl derivate, despite the similar size of the chloro and methyl substituents. The influence of the chloro and methyl substituents on the packing and on the thermal stability is demonstrated. All crystal structures were confirmed by dispersion-corrected DFT calculations. For the 4-chloro-5-methyl and the 4,5-dichloro derivatives the DFT calculations indicated that the observed polymorph should not be the thermodynamical one. However, no other polymorphs could be found in experimental polymorph screening, even using seeding with the corresponding isostructural phases. Obviously the DFT methods need further improvements.