Crystal structure determination by combined synchrotronpowder X-ray diffraction and crystal structure prediction: 1 : 1 l-ephedrine<scp>d</scp>-tartrate

Wu, Han; Habgood, Matthew; Parker, Julia; Reeves‐McLaren, Nik; Cockcroft, Jeremy K.; Vickers, Martin; West, Anthony R.; Jones, Alan G.

doi:10.1039/c2ce26097b

Cited by 15 publications

(13 citation statements)

References 42 publications

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“…The use of crystal energy landscapes to help characterize or add confidence to structures derived from powder X-ray diffraction is becoming well established. This varies from providing the first crystal structures of pigments (Schmidt et al, 2010) to determining the structure of a novel polymorph (Perrin et al, 2009) or the racemic form (Braun, Ardid-Candel et al, 2011) when single crystals can only be grown for other packings, to solving ambiguities in proton positions (Wu et al, 2013). Currently less established uses include solving the crystal structures from high-resolution 1 H solid-state NMR (Baias et al, 2013;Salager et al, 2010) or from electron diffraction patterns (Eddleston et al, 2013b).…”

Section: Because the Polymorphs Are Not Detected Or Structurally Charmentioning

confidence: 99%

Why don't we find more polymorphs?

Price

2013

Acta Crystallogr B Struct Sci Cryst Eng Mater

199

232

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Printed in Singapore -all rights reservedCrystal structure prediction (CSP) studies are not limited to being a search for the most thermodynamically stable crystal structure, but play a valuable role in understanding polymorphism, as shown by interdisciplinary studies where the crystal energy landscape has been explored experimentally and computationally. CSP usually produces more thermodynamically plausible crystal structures than known polymorphs. This article illustrates some reasons why: because (i) of approximations in the calculations, particularly the neglect of thermal effects (see x1.1); (ii) of the molecular rearrangement during nucleation and growth (see x1.2); (iii) the solidstate structures observed show dynamic or static disorder, stacking faults, other defects or are not crystalline and so represent more than one calculated structure (see x1.3); (iv) the structures are metastable relative to other molecular compositions (see x1.4); (v) the right crystallization experiment has not yet been performed (see x1.5) or (vi) cannot be performed (see x1.6) and the possibility (vii) that the polymorphs are not detected or structurally characterized (see x1.7). Thus, we can only aspire to a general predictive theory for polymorphism, as this appears to require a quantitative understanding of the kinetic factors involved in all possible multi-component crystallizations. For a specific molecule, analysis of the crystal energy landscape shows the potential complexity of its crystallization behaviour.

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Section: Because the Polymorphs Are Not Detected Or Structurally Charmentioning

confidence: 99%

Why don't we find more polymorphs?

Price

2013

Acta Crystallogr B Struct Sci Cryst Eng Mater

199

232

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“…This observation that some strongly hydrogen-bonded ionic motifs can give rise to a multitude of different three-dimensional packings, whereas others have more specific ways of packing leading to fewer competitive structures, has also been seen in some diastereomeric organic salts. 63 …”

Section: Discussionmentioning

confidence: 99%

Unraveling Complexity in the Solid Form Screening of a Pharmaceutical Salt: Why so Many Forms? Why so Few?

Braun

Lingireddy

Beidelschies³

et al. 2017

Crystal Growth & Design

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The solid form landscape of 5-HT2a antagonist 3-(4-(benzo[d]isoxazole-3-yl)piperazin-1-yl)-2,2-dimethylpropanoic acid hydrochloride (B5HCl) proved difficult to establish. Many crystalline materials were produced by solid form screening, but few forms readily grew high quality crystals to afford a clear picture or understanding of the solid form landscape. Careful control of crystallization conditions, a range of experimental methods, computational modeling of solvate structures, and crystal structure prediction were required to see potential arrangements of the salt in its crystal forms. Structural diversity in the solid form landscape of B5HCl was apparent in the layer structures for the anhydrate polymorphs (Forms I and II), dihydrate and a family of solvates with alcohols. The alcohol solvates, which provided a distinct packing from the neat forms and the dihydrate, form layers with conserved hydrogen bonding between B5HCl and the solvent, as well as stacking of the aromatic rings. The ability of the alcohol hydrocarbon moieties to efficiently pack between the layers accounted for the difficulty in growing some solvate crystals and the inability of other solvates to crystallize altogether. Through a combination of experiment and computation, the crystallization problems, form stability, and desolvation pathways of B5HCl have been rationalized at a molecular level.

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“…Over the last few years, these algorithms have been applied both by us and more extensively by others to a relatively wide variety of systems including single compound crystals [15,[29][30][31][32][33][34][35][36], co-crystals [14,[37][38][39], including chiral co-crystals [40,41], hydrates and solvates [42,43]. The codes have also been used separately, e.g.…”

Section: The Crystalpredictor and Crystaloptimizer Algorithmsmentioning

confidence: 99%

“…However, in the interests of clarity of presentation, we omit this complication from the mathematical descriptions provided in this chapter. 39 partitioning provides a mechanism for adjusting the number of degrees of freedom that have to be manipulated during the energy minimisation (see Sect. 3.2).…”

Section: Molecular Descriptionsmentioning

confidence: 99%

General Computational Algorithms for Ab Initio Crystal Structure Prediction for Organic Molecules

Pantelides

Adjiman

Kazantsev

2014

Topics in Current Chemistry

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The prediction of the possible crystal structure(s) of organic molecules is an important activity for the pharmaceutical and agrochemical industries, among others, due to the prevalence of crystalline products. This chapter considers the general requirements that crystal structure prediction (CSP) methodologies need to fulfil in order to be able to achieve reliable predictions over a wide range of organic systems. It also reviews the current status of a multistage CSP methodology that has recently proved successful for a number of systems of practical interest. Emphasis is placed on recent developments that allow a reconciliation of conflicting needs for, on the one hand, accurate evaluation of the energy of a proposed crystal structure and on the other hand, comprehensive search of the energy landscape for the reliable identification of all low-energy minima. Finally, based on the experience gained from this work, current limitations and opportunities for further research in this area are identified. We also consider issues relating to the use of empirical models derived from experimental data in conjunction with ab initio CSP.

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Crystal structure determination by combined synchrotronpowder X-ray diffraction and crystal structure prediction: 1 : 1 l-ephedrined-tartrate

Cited by 15 publications

References 42 publications

Why don't we find more polymorphs?

Why don't we find more polymorphs?

Unraveling Complexity in the Solid Form Screening of a Pharmaceutical Salt: Why so Many Forms? Why so Few?

General Computational Algorithms for Ab Initio Crystal Structure Prediction for Organic Molecules

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