Dimorphs of 4′-amino-4-hydroxy-2′-methylbiphenyl: Assessment of likelihood of polymorphism in flexible molecules

Dey, Archan; Desiraju, Gautam R.

doi:10.1039/b605751a

Cited by 15 publications

(10 citation statements)

References 19 publications

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“…In another similar result, we found that the biphenyl aminophenol 5 (Scheme 2) exists as two conformational polymorphs. [98] The kinetic form has the better interactions in terms of an infinite N À H···O À H···N À H···O À H chain stabilized by cooperative effects. It is known that this infinite hydrogen-bonded chain is the most favored synthon for aminophenols.…”

Section: Thermodynamic and Kinetic Crystallizationmentioning

confidence: 99%

Crystal Engineering: A Holistic View

Desiraju¹

2007

Angew Chem Int Ed

1,354

866

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Crystal engineering, the design of molecular solids, is the synthesis of functional solid-state structures from neutral or ionic building blocks, using intermolecular interactions in the design strategy. Hydrogen bonds, coordination bonds, and other less directed interactions define substructural patterns, referred to in the literature as supramolecular synthons and secondary building units. Crystal engineering has considerable overlap with supramolecular chemistry, X-ray crystallography, materials science, and solid-state chemistry and yet it is a distinct discipline in itself. The subject goes beyond the traditional divisions of organic, inorganic, and physical chemistry, and this makes for a very eclectic blend of ideas and techniques. The purpose of this Review is to highlight some current challenges in this rapidly evolving subject. Among the topics discussed are the nature of intermolecular interactions and their role in crystal design, the sometimes diverging perceptions of the geometrical and chemical models for a molecular crystal, the relationship of these models to polymorphism, knowledge-based computational prediction of crystal structures, and efforts at mapping the pathway of the crystallization reaction.

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Section: Thermodynamic and Kinetic Crystallizationmentioning

confidence: 99%

Crystal Engineering: A Holistic View

Desiraju¹

2007

Angew Chem Int Ed

1,354

866

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“….we have related the absence of polymorphism in this family to the presence of flexible groups that are also hydrogen bond donors and acceptors.'' 78 Do any of these correlations represent facts or fictions? One of the most enigmatic aspects of polymorphism is how the molecular structure of a compound relates to its ability to exhibit polymorphism.…”

Section: Molecular Structure and Polymorphism (Csd)mentioning

confidence: 99%

Facts and fictions about polymorphism

2015

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We present new facts about polymorphism based on (i) crystallographic data from the Cambridge Structural Database (CSD, a database built over 50 years of community effort), (ii) 229 solid form screens conducted at Hoffmann-La Roche and Eli Lilly and Company over the course of 8+ and 15+ years respectively and (iii) a dataset of 446 polymorphic crystals with energies and properties computed with modern DFT-d methods. We found that molecular flexibility or size has no correlation with the ability of a compound to be polymorphic. Chiral molecules, however, were found to be less prone to polymorphism than their achiral counterparts and compounds able to hydrogen bond exhibit only a slightly higher propensity to polymorphism than those which do not. Whilst the energy difference between polymorphs is usually less than 1 kcal mol(-1), conformational polymorphs are capable of differing by larger values (up to 2.5 kcal mol(-1) in our dataset). As overall statistics, we found that one in three compounds in the CSD are polymorphic whilst at least one in two compounds from the Roche and Lilly set display polymorphism with a higher estimate of up to three in four when compounds are screened intensively. Whilst the statistics provide some guidance of expectations, each compound constitutes a new challenge and prediction and realization of targeted polymorphism still remains a holy grail of materials sciences.

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“…Cognition of interaction preferences can guide to understand the thermodynamics and kinetics interplay in the polymorphic system. In some special cases, it can be observed that the less stable polymorph has better interactions, while the more stable polymorph shows better packing . From this context, quantification of interaction preferences was performed using the Hirshfeld surface analysis (Figure and Figure S12) for RT and HT-forms.…”

Section: Resultsmentioning

confidence: 99%

“…In some special cases, it can be observed that the less stable polymorph has better interactions, while the more stable polymorph shows better packing. 80 From this context, quantification of interaction preferences was performed using the Hirshfeld surface analysis (Figure 7 and Figure S12) 81 for RT and HT-forms. It revealed that strong hydrogen bonding interactions are more pronounced for RTform (37.8%) than HT-form (31.3%).…”

Section: Discovery Of Polymorphism and Their Thermalmentioning

confidence: 99%

Solid-State Phase Transition of Agomelatine–Phosphoric Acid Molecular Complexes along the Salt–Cocrystal Continuum: Ab Initio Powder X-ray Diffraction Structure Determination and DFT-D2 Analysis

Voguri

Ranga

Dey

et al. 2020

Crystal Growth & Design

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The solid-state phase transition of a multicomponent active pharmaceutical ingredient (M-APIs), composed of (1:1) agomelatine and phosphoric acid (AGL-P), is characterized using a set of complementary techniques: in situ variable temperature powder X-ray diffraction (VT-PXRD), thermal analysis, spectroscopic techniques, and hot stage microscopy (HSM). It is observed that these dimorphic forms (AGL-P RT-form and HT-form) are enantiotropic and reversible in nature. The salt–cocrystal continuum of this system is demonstrated using ab initio powder XRD structure determination (SDPD) and dispersion corrected density functional theory (DFT-D2) analysis. Furthermore, this solid-state phase transition can be inferred as a martensitic-like transformation, where simultaneous proton migration and small conformational switching trigger the concerted molecular displacements of entire layers, leading to microscopic crystal contraction.

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Dimorphs of 4′-amino-4-hydroxy-2′-methylbiphenyl: Assessment of likelihood of polymorphism in flexible molecules

Cited by 15 publications

References 19 publications

Crystal Engineering: A Holistic View

Crystal Engineering: A Holistic View

Facts and fictions about polymorphism

Solid-State Phase Transition of Agomelatine–Phosphoric Acid Molecular Complexes along the Salt–Cocrystal Continuum: Ab Initio Powder X-ray Diffraction Structure Determination and DFT-D2 Analysis

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