From racemic compounds through metastable to stable racemic conglomerates: crystallization features of chiral halogen and cyano monosubstituted phenyl glycerol ethers

Бредихин, А. А.; Бредихина, З. А.; Akhatova, Flyura S.; Zakharychev, Dmitry V.; Polyakova, E. V.

doi:10.1016/j.tetasy.2009.09.008

Cited by 20 publications

(20 citation statements)

References 20 publications

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“…Since the end of the 19th century, it has been highlighted that three basic situations can be encountered in such diagrams: 1) the racemic compound, consisting of a 1:1 defined compound of the two enantiomers usually related by centrosymmetry in the crystal lattice; 2) the conglomerate, made of a mixture of enantiopure crystals and 3) the solid solution, depicting various degrees of chiral discrimination, giving rise to mixed crystals (Figure ). The complexity of such diagrams increases if polymorphism occurs in the system or if metastable equilibria are considered …”

Section: Introductionmentioning

confidence: 99%

“…The complexity of such diagrams increases if polymorphism [9][10][11] occurs in the system or if metastable equilibria are considered. [12][13][14] Despite progress in the solid-statec haracterisationo fc hiral systems in recent decades, [15][16][17][18] the mechanisms of chiral selectivity in crystalline architectures are insufficiently understood. For instance, the prevalence of racemic compounds (depicted in ca.…”

Section: Introductionmentioning

confidence: 99%

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Prenucleation Self‐Assembly and Chiral Discrimination Mechanisms during Solution Crystallisation of Racemic Diprophylline

Brandel

Cartigny

Coquerel

et al. 2016

Chemistry A European J

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This version is available at https://strathprints.strath.ac.uk/58510/ Strathprints is designed to allow users to access the research output of the University of Strathclyde. Unless otherwise explicitly stated on the manuscript, Copyright © and Moral Rights for the papers on this site are retained by the individual authors and/or other copyright owners. Please check the manuscript for details of any other licences that may have been applied. You may not engage in further distribution of the material for any profitmaking activities or any commercial gain. You may freely distribute both the url (https://strathprints.strath.ac.uk/) and the content of this paper for research or private study, educational, or not-for-profit purposes without prior permission or charge.Any correspondence concerning this service should be sent to the Strathprints administrator: strathprints@strath.ac.ukThe Strathprints institutional repository (https://strathprints.strath.ac.uk) is a digital archive of University of Strathclyde research outputs. It has been developed to disseminate open access research outputs, expose data about those outputs, and enable the management and persistent access to Strathclyde's intellectual output. FULL PAPER Pre-Nucleation Self-Assembly and Chiral Discrimination Mechanisms during Solution Crystallization of Racemic DiprophyllineClément Brandel,* [a] Yohann Cartigny, [a] Gérard Coquerel, [a] Joop H. ter Horst, [b] and Samuel Petit [a] Abstract: The crystallization behavior of (RS)-Diprophylline (DPL) in two different solvents is investigated in order to assess the incidence of solvated pre-associations on nucleation, crystal growth and chiral discrimination. In the solvated state, Raman spectroscopy shows that dimeric associations similar to those depicted in the crystalline solid solution (ssRII) predominate in isopropyl alcohol (IPA), which may account for the systematic spontaneous nucleation of this crystal form from this solvent. By contrast, spontaneous nucleation in dimethylformamide yields the stable racemic compound RI, consistently with the distinct features of the Raman spectrum collected in this solvent. A crystal growth study of ssRII in IPA reveals that the crystal habitus is impacted by the solution enantiomeric excess which is explained by an increased competition between homo and heterochiral pre-associations. This is supported by a molecular modelling study on the enantiomeric selectivity of the DPL crystal lattices. The combination of assessment methods on solution chemistry, nucleation and chiral discrimination provides methodological tools from which the occurrence of solid solutions can be rationalized.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prenucleation Self‐Assembly and Chiral Discrimination Mechanisms during Solution Crystallisation of Racemic Diprophylline

Brandel

Cartigny

Coquerel

et al. 2016

Chemistry A European J

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“…samples could be carried out following the standard procedure of Pearson correlation coefficient r(A R ,A A ) computation between two vectors {A i R } and {A i A }. 17 The value r(A R ,A A ) ¼ 1 corresponds to a perfect correlation (identity in our case) of two vectors (spectra). For rac-and (S)-TM sample pairs the correlation coefficient is better than r $ 0.99.…”

Section: Ir Spectra Comparisonmentioning

confidence: 90%

Chiral drugtimolol maleate as a continuous solid solution: Thermochemical and single crystal X-ray evidence

et al. 2012

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Thermochemical properties of binary mixtures of the popular chiral drug timolol maleate (TM) were investigated by differential scanning calorimetry. It was found that there are no eutectic points on the melting phase diagram, and the enantiomeric components form a continual set of solid solutions over a wide concentration range. The crystal structure of heterochiral racemic TM is essentially isostructural with that of the homochiral (S)-TM, having close cell parameters but containing a crystallographic inversion centre. The crystal structure of the homochiral TM contains two symmetry independent molecules in the unit cell. These molecules have different conformations but are approximate mirror images of each other in the crystal lattice. Within the homochiral crystals only one site of two changes its nature in the heterochiral crystals. The solid solution of TM could be treated as the solid solution of a regular racemic compound and a pure enantiomer.

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“…Racemic and ( S ) - 3-(chlorophenoxy)propane-1,2-diols, were prepared from corresponding phenol and racemic or ( S )-3-chloropropane-1,2-diol by analogy to published procedures:…”

Section: Methodsmentioning

confidence: 99%

Crystal Landscape of Chiral Drug Chlorphenesin and Its Structural Analogues: Polymorphism of Racemic and Enantiopure Samples, Metastable and Stable Racemic Conglomerates, Diverse in Unity Crystal Motifs

Бредихин

Zakharychev

Губайдуллин

et al. 2021

Crystal Growth & Design

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The phase behavior of chiral API Chlorphenesin 1 and its structural analogues 2 and 3 was investigated by DSC and PXRD methods. For the entire family of compounds 1–3, many crystalline modifications have been found for the first time. It has been shown that both racemic and enantiopure samples 1 form stable and metastable phases; racemic meta-derivative 2, along with stable and metastable racemic compounds, is capable of forming a metastable racemic conglomerate. In the case of the ortho-derivative 3, metastable crystalline racemic compounds were not detected, while both stable and metastable homochiral forms are capable of forming racemic conglomerates. For compounds 1–3, the free energies of metastable forms were estimated experimentally relative to the thermodynamically most stable racemic compounds. All racemic compounds of chloro- and methyl-substituted chlorphenesin analogues, studied by X-ray diffraction analysis, form a common supramolecular motif, while three different crystal organizations have been identified for enantiopure forms. In 7 cases out of the 9 studied, the crystal packing is formed with the participation of two symmetry independent molecules. Apparently, both the unusual diversity of the crystalline landscape and the increased frequency of Z′ > 1 cases in the series under study have a common reason and reflect the variety of ways for intermolecular hydrogen bond formation in the crystals of aryl glycerol ethers.

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From racemic compounds through metastable to stable racemic conglomerates: crystallization features of chiral halogen and cyano monosubstituted phenyl glycerol ethers

Cited by 20 publications

References 20 publications

Prenucleation Self‐Assembly and Chiral Discrimination Mechanisms during Solution Crystallisation of Racemic Diprophylline

Prenucleation Self‐Assembly and Chiral Discrimination Mechanisms during Solution Crystallisation of Racemic Diprophylline

Chiral drugtimolol maleate as a continuous solid solution: Thermochemical and single crystal X-ray evidence

Crystal Landscape of Chiral Drug Chlorphenesin and Its Structural Analogues: Polymorphism of Racemic and Enantiopure Samples, Metastable and Stable Racemic Conglomerates, Diverse in Unity Crystal Motifs

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