Unmasking a third polymorph of a benchmark crystal-structure-prediction compound.
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ABSTRACT:
SUBMITTER: Roy S
PROVIDER: S-EPMC3140642 | biostudies-literature | 2009
REPOSITORIES: biostudies-literature
Publications
Unmasking a third polymorph of a benchmark crystal-structure-prediction compound.
Roy Saikat S Matzger Adam J AJ
Angewandte Chemie (International ed. in English) 20090101 45
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Project description:In the structure of the title complex, [Fe(C5H7O2)3] or Fe(acac)3, the asymmetric unit contains one mol-ecule in a general position. The coordination sphere of the Fe(III) atom is that of a slightly distorted octahedron. The crystal under investigation was a two-component pseudo-merohedral twin in the monoclinic system with a β angle close to 90°. Twin law [100/0-10/00-1] reduced the R1 residual [I > 2σ(I)] from 0.0769 to 0.0312, and the mass ratio of twin components refined to 0.8913 (5):0.1087 (5). In the crystal, mol-ecules are arranged in sheets normal to [001] via non-classical C-H⋯O hydrogen bonding. No other significant inter-molecular inter-actions are observed. The structure is a new polymorph of Fe(acac)3 and is isotypic with one polymorph of its gallium analog.
| S-EPMC4719847 | biostudies-literature
Project description:Organic molecules, such as pharmaceuticals, agro-chemicals and pigments, frequently form several crystal polymorphs with different physicochemical properties. Finding polymorphs has long been a purely experimental game of trial-and-error. Here we utilize in silico polymorph screening in combination with rationally planned crystallization experiments to study the polymorphism of the pharmaceutical compound Dalcetrapib, with 10 torsional degrees of freedom one of the most flexible molecules ever studied computationally. The experimental crystal polymorphs are found at the bottom of the calculated lattice energy landscape, and two predicted structures are identified as candidates for a missing, thermodynamically more stable polymorph. Pressure-dependent stability calculations suggested high pressure as a means to bring these polymorphs into existence. Subsequently, one of them could indeed be crystallized in the 0.02 to 0.50 GPa pressure range and was found to be metastable at ambient pressure, effectively derisking the appearance of a more stable polymorph during late-stage development of Dalcetrapib.
| S-EPMC4525153 | biostudies-literature
Project description:A third crystalline form of the title compound, C9H10O4, crystallizing in the centrosymmetric monoclinic space group P21/c, has been identified during screening for co-crystals. The asymmetric unit comprises a non-planar independent mol-ecule with a synplanar conformation of the OH group. The sterically bulky o-meth-oxy substituents force the carb-oxy group to be twisted away from the plane of the benzene ring by 74.10 (6)°. The carb-oxy group exhibits the acidic H atom disordered over two sites between two O atoms. A similar situation has been found for the second tetra-gonal polymorph reported [Portalone (2011 ▸). Acta Cryst. E67, o3394-o3395], in which mol-ecules with the OH group in a synplanar conformation form dimeric units via strong O-H⋯O hydrogen bonds. In contrast, in the first ortho-rhom-bic form reported [Swaminathan et al. (1976 ▸). Acta Cryst. B32, 1897-1900; Bryan & White (1982 ▸). Acta Cryst. B38, 1014-1016; Portalone (2009 ▸). Acta Cryst. E65, o327-o328], the mol-ecular components do not form conventional dimeric units, as an anti-planar conformation adopted by the OH group favors the association of mol-ecules in chains stabilized by linear O-H⋯O hydrogen bonds.
| S-EPMC7784654 | biostudies-literature
Project description:Understanding the behavior and properties of molecules assembled in thin layers requires knowledge of their crystalline packing. The drug phenytoin (5,5-diphenylhydantoin) is one of the compounds that can be grown as a surface induced polymorph. By using grazing incidence X-ray diffraction, the monoclinic unit cell of the new form II can be determined, but, due to crystal size and the low amount of data, a full solution using conventional structure solving strategies fails. In this work, the full solution has been obtained by combining computational structure generation and experimental results. The comparison between the bulk and the new surface induced phase reveals significant packing differences of the hydrogen-bonding network, which might be the reason for the faster dissolution of form II with respect to form I. The results are very satisfactory, and the method might be adapted for other systems, where, due to the limited amount of experimental data, one must rely on additional approaches to gain access to more detailed information to understand the solid-state behavior.
| S-EPMC6839513 | biostudies-literature
Project description:The title mol-ecular salt, C6H8N(+)·C6H2N3O7 (-) (systematic name: 3-methyl-pyridinium 2,4,6-tri-nitro-phenolate), crystallizes in the triclinic space group P-1. The crystal structure of the monoclinic polymorph (space group P21/n) has been reported [Stilinovic & Kaitner (2011 ▸). Cryst. Growth Des. 11, 4110-4119]. In the crystal, the anion and cation are linked via bifurcated N-H⋯(O,O) hydrogen bonds, enclosing an R 1 (2)(6) graph-set motif. These units are linked via C-H⋯O hydrogen bonds, forming a three-dimensional framework. Within the framework there are π-π inter-actions present, involving inversion-related picrate anions and inversion-related pyridinium cations, with inter-centroid distances of 3.7389 (14) and 3.560 (2) Å, respectively.
| S-EPMC4647397 | biostudies-literature
Project description:In an attempt to grow 8-hy-droxy-quinoline-acetamino-phen co-crystals from equimolar amounts of conformers in a chloro-form-ethanol solvent mixture at room temperature, the title compound, C9H7NO, was obtained. The mol-ecule is planar, with the hy-droxy H atom forming an intra-molecular O-H⋯N hydrogen bond. In the crystal, mol-ecules form centrosymmetric dimers via two O-H⋯N hydrogen bonds. Thus, the hy-droxy H atoms are involved in bifurcated O-H⋯N hydrogen bonds, leading to the formation of a central planar four-membered N2H2 ring. The dimers are bound by inter-molecular π-π stacking [the shortest C⋯C distance is 3.2997 (17) Å] and C-H⋯π inter-actions into a three-dimensional framework. The crystal grown represents a new monoclinic polymorph in the space group P21/n. The mol-ecular structure of the present monoclinic polymorph is very similar to that of the ortho-rhom-bic polymorph (space group Fdd2) studied previously [Roychowdhury et al. (1978 ▶). Acta Cryst. B34, 1047-1048; Banerjee & Saha (1986 ▶). Acta Cryst. C42, 1408-1411]. The structures of the two polymorphs are distinguished by the different geometries of the hydrogen-bonded dimers, which in the crystal of the ortho-rhom-bic polymorph possess twofold axis symmetry, with the central N2H2 ring adopting a butterfly conformation.
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Project description:A new polymorph of the mycotoxin alternariol is reported and characterized by single crystal X-ray diffraction. Structural data, Hirshfeld surface analysis, and 2D fingerprint plots are used to compare differences in the intermolecular interactions of the orthorhombic Pca21 Form I (previously reported) and the monoclinic P21/c Form II (herein reported). The polymorphs have small differences in planarity-7.55° and 2.19° between the terminal rings for Form I and Form II, respectively-that brings about significant differences in the crystal packing and O-H … H interactions.
| S-EPMC9374539 | biostudies-literature
Project description:The title mol-ecular salt, C6H8N(+)·C6H2N3O7 (-) (systematic name: 2-methyl-pyridinium 2,4,6-tri-nitro-phenolate), crystallizes with two cations and two anions in the asymmetric unit. In the crystal, the cations are linked to the anions via bifurcated N-H⋯(O,O) hydrogen bonds, generating R 1 (2)(6) graph-set motifs. Numerous C-H⋯O hydrogen bonds are observed between these cation-anion pairs, which result in a three-dimensional network. In addition, weak aromatic π-π stacking between the 2-methyl-pyridinium rings [inter-centroid distance = 3.8334 (19) Å] and very weak stacking [inter-centroid distance = 4.0281 (16) Å] between inversion-related pairs of picrate anions is observed. The title salt is a second triclinic polymorph of the structure (also with Z' = 2) reported earlier [Anita et al. (2006). Acta Cryst. C62, o567-o570; Chan et al. (2014 ▸). CrystEngComm, 16, 4508-4538]. In the title compound, the cations and anions display a chequerboard arrangement when viewed down [100], whereas in the first polymorph, (010) layers of alternating cations and anions are apparent in a [100] view. It is inter-esting that the unit-cell lengths are almost identical for the two polymorphs, although the inter-axial angles are quite different.
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Project description:A novel method that enables single-crystal diffraction data to be obtained from a powder sample is presented. A suspension of LiCoPO(4) microrods was subjected to a frequency-modulated dynamic elliptical magnetic field to align the microrods; the alignment achieved was consolidated by photopolymerization of the suspending UV-curable monomer. The composite thus obtained (referred to as a pseudo single crystal) gave rise to X-ray diffraction data from which the crystal structure was solved using the standard method for single-crystal X-ray analyses. The structure determined was in good agreement with that reported using a conventional single crystal.
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Project description:Drug-induced blockade of the human ether-à-go-go-related gene (hERG) channel is today considered the main cause of cardiotoxicity in postmarketing surveillance. Hence, several ligand-based approaches were developed in the last years and are currently employed in the early stages of a drug discovery process for in silico cardiac safety assessment of drug candidates. Herein, we present the first structure-based classifiers able to discern hERG binders from nonbinders. LASSO regularized support vector machines were applied to integrate docking scores and protein-ligand interaction fingerprints. A total of 396 models were trained and validated based on: (i) high-quality experimental bioactivity information returned by 8337 curated compounds extracted from ChEMBL (version 25) and (ii) structural predictor data. Molecular docking simulations were performed using GLIDE and GOLD software programs and four different hERG structural models, namely, the recently published structures obtained by cryoelectron microscopy (PDB codes: 5VA1 and 7CN1) and two published homology models selected for comparison. Interestingly, some classifiers return performances comparable to ligand-based models in terms of area under the ROC curve (AUCMAX = 0.86 ± 0.01) and negative predictive values (NPVMAX = 0.81 ± 0.01), thus putting forward the herein proposed computational workflow as a valuable tool for predicting hERG-related cardiotoxicity without the limitations of ligand-based models, typically affected by low interpretability and a limited applicability domain. From a methodological point of view, our study represents the first example of a successful integration of docking scores and protein-ligand interaction fingerprints (IFs) through a support vector machine (SVM) LASSO regularized strategy. Finally, the study highlights the importance of using hERG structural models accounting for ligand-induced fit effects and allowed us to select the best-performing protein conformation (made available in the Supporting Information, SI) to be employed for a reliable structure-based prediction of hERG-related cardiotoxicity.
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