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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.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.

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

Supramolecular synthons in quercetin cocrystal landscapes. All the members of this synthon library may be interpreted based on O—H⋯O and/or O—H⋯N hydrogen bonding patterns, but each synthon is distinct from any of the others based on topological considerations.
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fig3: Supramolecular synthons in quercetin cocrystal landscapes. All the members of this synthon library may be interpreted based on O—H⋯O and/or O—H⋯N hydrogen bonding patterns, but each synthon is distinct from any of the others based on topological considerations.

Mentions: Quercetin has five hydroxy groups (Fig. 1 ▸) and the mutual orientations of these groups provide a variety of putative conformations that constitute a virtual conformational library (supporting information). This scenario is further complicated by the conformational possibilities brought about with the flexible C-ring. We performed extensive cocrystallization experiments with dibasic coformers (supporting information). These crystal structures are characterized by several O—H⋯N and/or O—H⋯O based supramolecular synthons which are all rather distinctive and lead to structure types that we refer to in this paper as nonporous, porous and helical within the extended domain of the quercetin cocrystal landscapes. There are other synthon possibilities which were revealed in later cocrystal screening experiments, giving a hint about the virtual nature of this library. Figs. 2 ▸ and 3 ▸ illustrate quercetin conformations and a schematic representation of the supramolecular synthons discussed here. In general, the second (OH2) and third (OH3) hydroxy groups of quercetin are conformationally locked by intramolecular hydrogen bonding, while OH1, OH4 and OH5 are responsible for the supramolecular development of various intricate hydrogen bonding patterns in the crystal structures. The supporting information gives a list of 12 conformations and their energies. It is interesting that the most stable conformation (Conf 2B) does not feature in the experimental crystal structures. This could be because of a trade-off between intra- and intermolecular factors.


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

Dubey R, Desiraju GR - IUCrJ (2015)

Supramolecular synthons in quercetin cocrystal landscapes. All the members of this synthon library may be interpreted based on O—H⋯O and/or O—H⋯N hydrogen bonding patterns, but each synthon is distinct from any of the others based on topological considerations.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig3: Supramolecular synthons in quercetin cocrystal landscapes. All the members of this synthon library may be interpreted based on O—H⋯O and/or O—H⋯N hydrogen bonding patterns, but each synthon is distinct from any of the others based on topological considerations.
Mentions: Quercetin has five hydroxy groups (Fig. 1 ▸) and the mutual orientations of these groups provide a variety of putative conformations that constitute a virtual conformational library (supporting information). This scenario is further complicated by the conformational possibilities brought about with the flexible C-ring. We performed extensive cocrystallization experiments with dibasic coformers (supporting information). These crystal structures are characterized by several O—H⋯N and/or O—H⋯O based supramolecular synthons which are all rather distinctive and lead to structure types that we refer to in this paper as nonporous, porous and helical within the extended domain of the quercetin cocrystal landscapes. There are other synthon possibilities which were revealed in later cocrystal screening experiments, giving a hint about the virtual nature of this library. Figs. 2 ▸ and 3 ▸ illustrate quercetin conformations and a schematic representation of the supramolecular synthons discussed here. In general, the second (OH2) and third (OH3) hydroxy groups of quercetin are conformationally locked by intramolecular hydrogen bonding, while OH1, OH4 and OH5 are responsible for the supramolecular development of various intricate hydrogen bonding patterns in the crystal structures. The supporting information gives a list of 12 conformations and their energies. It is interesting that the most stable conformation (Conf 2B) does not feature in the experimental crystal structures. This could be because of a trade-off between intra- and intermolecular factors.

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.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.

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