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Combinatorial selection of molecular conformations and supramolecular synthons in quercetin cocrystal landscapes: a route to ternary solids.

Dubey R, Desiraju GR - IUCrJ (2015)

Bottom Line: The crystallization of 28 binary and ternary cocrystals of quercetin with dibasic coformers is analyzed in terms of a combinatorial selection from a solution of preferred molecular conformations and supramolecular synthons.Variability in molecular conformation and synthon structure led to an increase in the energetic and structural space around the crystallization event.In the landscape context, we develop a strategy for the isolation of ternary cocrystals with the use of auxiliary template molecules to reduce the molecular and supramolecular 'confusion' that is inherent in a molecule like quercetin.

View Article: PubMed Central - HTML - PubMed

Affiliation: Solid State and Structural Chemistry Unit, Indian Institute of Science , Bangalore 560 012, India.

ABSTRACT
The crystallization of 28 binary and ternary cocrystals of quercetin with dibasic coformers is analyzed in terms of a combinatorial selection from a solution of preferred molecular conformations and supramolecular synthons. The crystal structures are characterized by distinctive O-H⋯N and O-H⋯O based synthons and are classified as nonporous, porous and helical. Variability in molecular conformation and synthon structure led to an increase in the energetic and structural space around the crystallization event. This space is the crystal structure landscape of the compound and is explored by fine-tuning the experimental conditions of crystallization. In the landscape context, we develop a strategy for the isolation of ternary cocrystals with the use of auxiliary template molecules to reduce the molecular and supramolecular 'confusion' that is inherent in a molecule like quercetin. The absence of concomitant polymorphism in this study highlights the selectivity in conformation and synthon choice from the virtual combinatorial library in solution.

No MeSH data available.


Related in: MedlinePlus

Porous molecular arrangements in quercetin cocrystal landscapes; QUE:TMP (left), QUE:44BP (middle), QUE:DPE (right). Compounds are color coded: green – quercetin; blue – coformer.
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fig4: Porous molecular arrangements in quercetin cocrystal landscapes; QUE:TMP (left), QUE:44BP (middle), QUE:DPE (right). Compounds are color coded: green – quercetin; blue – coformer.

Mentions: The quercetin–4,4′-bipyridine cocrystal system (QUE:44BP) has four crystal forms. Three of them are porous, with basically the same structure as the porous QUE:TMP crystals, and have 1:1 stoichiometry. As in QUE:TMP, these forms have the same conformation Conf 5B and the same synthon E. These crystal structures accommodate 1,4-dioxane, thf and even coformer (44BP) as a guest in the larger porous pocket (Fig. 4 ▸). When QUE and 44BP were taken in 1:4 ratios in solution for crystallization, a fourth form was obtained in which QUE switches its molecular conformation to the high energy Conf 7B. This crystal form is a 1:3 QUE:44BP monohydrate with masked synthon F where water is involved in complex hydrogen bond patterns. MacGillivray et al. have utilized the appropriate term masked synthon to describe a situation wherein water actively participates in the development of the supramolecular synthon (Sander et al., 2013 ▸). In the next step, we replaced the 44BP coformer with 1,2-bis(4-pyridyl)ethylene (DPE-I) and explored its corresponding structural space. The QUE:DPE-I landscape contains five crystal forms – two anhydrates and one solvate each of 1,4-dioxane, thf and DMF. The latter pseudopolymorphic structures are all porous with the solvents situated in the open pockets. Extending the argument, we have described recently that replacement of DPE-I with 1,2-bis(4-pyridyl)ethane, DPE-II, can extend the structural landscape (Dubey & Desiraju, 2015 ▸). In the present study we made cocrystals of QUE with DPE-II and also with 4,4′-azopyridine (44AP), which is chemically similar to DPE-I and DPE-II. We found the same conformation Conf 6B and porous synthon E in these structures.


Combinatorial selection of molecular conformations and supramolecular synthons in quercetin cocrystal landscapes: a route to ternary solids.

Dubey R, Desiraju GR - IUCrJ (2015)

Porous molecular arrangements in quercetin cocrystal landscapes; QUE:TMP (left), QUE:44BP (middle), QUE:DPE (right). Compounds are color coded: green – quercetin; blue – coformer.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4491312&req=5

fig4: Porous molecular arrangements in quercetin cocrystal landscapes; QUE:TMP (left), QUE:44BP (middle), QUE:DPE (right). Compounds are color coded: green – quercetin; blue – coformer.
Mentions: The quercetin–4,4′-bipyridine cocrystal system (QUE:44BP) has four crystal forms. Three of them are porous, with basically the same structure as the porous QUE:TMP crystals, and have 1:1 stoichiometry. As in QUE:TMP, these forms have the same conformation Conf 5B and the same synthon E. These crystal structures accommodate 1,4-dioxane, thf and even coformer (44BP) as a guest in the larger porous pocket (Fig. 4 ▸). When QUE and 44BP were taken in 1:4 ratios in solution for crystallization, a fourth form was obtained in which QUE switches its molecular conformation to the high energy Conf 7B. This crystal form is a 1:3 QUE:44BP monohydrate with masked synthon F where water is involved in complex hydrogen bond patterns. MacGillivray et al. have utilized the appropriate term masked synthon to describe a situation wherein water actively participates in the development of the supramolecular synthon (Sander et al., 2013 ▸). In the next step, we replaced the 44BP coformer with 1,2-bis(4-pyridyl)ethylene (DPE-I) and explored its corresponding structural space. The QUE:DPE-I landscape contains five crystal forms – two anhydrates and one solvate each of 1,4-dioxane, thf and DMF. The latter pseudopolymorphic structures are all porous with the solvents situated in the open pockets. Extending the argument, we have described recently that replacement of DPE-I with 1,2-bis(4-pyridyl)ethane, DPE-II, can extend the structural landscape (Dubey & Desiraju, 2015 ▸). In the present study we made cocrystals of QUE with DPE-II and also with 4,4′-azopyridine (44AP), which is chemically similar to DPE-I and DPE-II. We found the same conformation Conf 6B and porous synthon E in these structures.

Bottom Line: The crystallization of 28 binary and ternary cocrystals of quercetin with dibasic coformers is analyzed in terms of a combinatorial selection from a solution of preferred molecular conformations and supramolecular synthons.Variability in molecular conformation and synthon structure led to an increase in the energetic and structural space around the crystallization event.In the landscape context, we develop a strategy for the isolation of ternary cocrystals with the use of auxiliary template molecules to reduce the molecular and supramolecular 'confusion' that is inherent in a molecule like quercetin.

View Article: PubMed Central - HTML - PubMed

Affiliation: Solid State and Structural Chemistry Unit, Indian Institute of Science , Bangalore 560 012, India.

ABSTRACT
The crystallization of 28 binary and ternary cocrystals of quercetin with dibasic coformers is analyzed in terms of a combinatorial selection from a solution of preferred molecular conformations and supramolecular synthons. The crystal structures are characterized by distinctive O-H⋯N and O-H⋯O based synthons and are classified as nonporous, porous and helical. Variability in molecular conformation and synthon structure led to an increase in the energetic and structural space around the crystallization event. This space is the crystal structure landscape of the compound and is explored by fine-tuning the experimental conditions of crystallization. In the landscape context, we develop a strategy for the isolation of ternary cocrystals with the use of auxiliary template molecules to reduce the molecular and supramolecular 'confusion' that is inherent in a molecule like quercetin. The absence of concomitant polymorphism in this study highlights the selectivity in conformation and synthon choice from the virtual combinatorial library in solution.

No MeSH data available.


Related in: MedlinePlus