Aniline–phenol recognition: from solution through supramolecular synthons to cocrystals

Mukherjee, Arijit; Dixit, Karuna; Sarma, Siddhartha P.; Desiraju, Gautam R.

doi:10.1107/s2052252514012081

Cited by 58 publications

(53 citation statements)

References 48 publications

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“…45) Predictions based on structural information offer insights into potential cocrystal arrangements and appropriate coformer choice. 46,47) Structure predictions based on synthon concepts or functional group compatibility are valuable for designing new cocrystals because various APIs and coformers form cocrystals through a network of non-covalent and non-ionic interactions, such as hydrogen bonding and supramolecular synthon, between certain functional groups. Crystal structure information resources, such as the Cambridge Structural Database, assist the search for stable hydrogen bonding motifs to form cocrystals.…”

Section: Screening and Prediction Of Cocrystal Formationmentioning

confidence: 99%

Characterization and Quality Control of Pharmaceutical Cocrystals

Izutsu¹,

Koide²,

Takata

et al. 2016

Chem. Pharm. Bull.

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Recent active research and new regulatory guidance on pharmaceutical cocrystals have increased the rate of their development as promising approaches to improve handling, storage stability, and bioavailability of poorly soluble active pharmaceutical ingredients (APIs). However, their complex structure and the limited amount of available information related to their performance may require development strategies that differ from those of single-component crystals to ensure their clinical safety and efficacy. This article highlights current methods of characterizing pharmaceutical cocrystals and approaches to controlling their quality. Different cocrystal regulatory approaches between regions are also discussed. The physical characterization of cocrystals should include elucidating the structure of their objective crystal form as well as their possible variations (e.g., polymorphs, hydrates). Some solids may also contain crystals of individual components. Multiple processes to prepare pharmaceutical cocrystals (e.g., crystallization from solutions, grinding) vary in their applicable ingredients, scalability, and characteristics of resulting solids. The choice of the manufacturing method affects the quality control of particular cocrystals and their formulations. In vitro evaluation of the properties that govern clinical performance is attracting increasing attention in the development of pharmaceutical cocrystals. Understanding and mitigating possible factors perturbing the dissolution and/ or dissolved states, including solution-mediated phase transformation (SMPT) and precipitation from supersaturated solutions, are important to ensure the bioavailability of orally administrated lower-solubility APIs. The effect of polymer excipients on the performance of APIs emphasizes the relevance of formulation design for appropriate use.

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Section: Screening and Prediction Of Cocrystal Formationmentioning

confidence: 99%

Characterization and Quality Control of Pharmaceutical Cocrystals

Izutsu¹,

Koide²,

Takata

et al. 2016

Chem. Pharm. Bull.

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show abstract

“…These larger units are the precursors to stoichiometric quaternary cocrystals, of which six are reported in this paper. While there is no spectroscopic evidence as yet for the existence of these LSAMs in solution (unlike in other cases already reported; Mukherjee et al, 2014), the fact that there is so much fidelity between the ternary and quaternary crystal structures suggests the stability of the LSAMs in solution. We also note the degree of reversibility among synthons in solution.…”

Section: Discussionmentioning

confidence: 60%

“…The concepts of the supramolecular synthon and the LSAM are not merely restricted to the understanding of crystal structures. Recent studies show that some of these smaller and larger synthons exist in solution prior to crystallization (Mukherjee et al, 2014). The build-up of a crystal from individual molecules may well be considered as occurring through a smooth and systematic build-up in structural complexity.…”

Section: Introductionmentioning

confidence: 99%

Quaternary cocrystals: combinatorial synthetic strategies based on long-range synthon Aufbau modules (LSAM)

Dubey

Mir

Desiraju

2016

IUCrJ

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“…3b shows the molecular arrangement in the hydrate form down the ab plane. Here, the primary structural motifs involving short and highly directional strong hydrogen bonds generate different types of cyclic tetrameric (R 1 and R 2 ) and hexameric (R 3 and R 4 ) synthons (Desiraju and co-workers 21 have discussed about the tetrameric and hexameric supramolecular synthons associated with a strong N-H⋯O hydrogen bond for aniline-phenol cocrystals). In this case, all the cyclic rings are interconnected with each other.…”

Section: Resultsmentioning

confidence: 99%

Solvatomorphism in (Z)-4-fluoro-N′-(3-fluorophenyl)benzimidamide: the role of intermolecular O–H⋯F interaction

Dey

Chopra

2016

CrystEngComm

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The synthesized compound (Z)-4-fluoro-N′-(3-fluorophenyl)benzimidamide exhibits solvatomorphism in the solid state. The anhydrous and the hydrate forms were obtained at room temperature from slow evaporation of cyclohexane and hexane solvents, respectively. Both forms crystallize in the triclinic P1 with two symmetry-independent molecules in the asymmetric unit. The crystal packing of the anhydrous form is stabilized via a strong N-H⋯N chain, whereas the hydrate form is stabilized via a strong (N-H⋯N)-(N-H⋯O)-(O-H⋯N) chain. The water molecule plays an important role in the crystal packing by the formation of "extremely short" N-H⋯O and O-H⋯N hydrogen bonds, which are further supported by weak O-H⋯F-C and C-H⋯O interactions. The basic structural building motifs were structurally and energetically equivalent in both forms. PIXEL and QTAIM approaches provide quantitative insights into the nature and energetics of strong as well as weak intermolecular interactions. The NCI descriptor shows the "attractive" nature of the rarely observed O-H⋯F interaction. The thermal stabilities of the solvatomorphs were characterized via differential scanning calorimetry, hot stage microscopy, and thermogravimetric analysis. Hirshfeld surface analysis and 2D fingerprint plots of the individual molecules present in both forms differentiate the trends in crystal packing as well as the contribution from the different intermolecular interactions.

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Aniline–phenol recognition: from solution through supramolecular synthons to cocrystals

Cited by 58 publications

References 48 publications

Characterization and Quality Control of Pharmaceutical Cocrystals

Characterization and Quality Control of Pharmaceutical Cocrystals

Quaternary cocrystals: combinatorial synthetic strategies based on long-range synthon Aufbau modules (LSAM)

Solvatomorphism in (Z)-4-fluoro-N′-(3-fluorophenyl)benzimidamide: the role of intermolecular O–H⋯F interaction

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