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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

Ternary design strategy. TTF (top) and PYR (lower) as template molecules in QUE:44BP and QUE:DPE-I cocrystals. These crystal structures also highlight tghe virtual selection of Conf 6B and synthon B.
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fig8: Ternary design strategy. TTF (top) and PYR (lower) as template molecules in QUE:44BP and QUE:DPE-I cocrystals. These crystal structures also highlight tghe virtual selection of Conf 6B and synthon B.

Mentions: The design strategy for ternary solids depends upon the QUE:44BP landscape in which there are consistent appearances of Conf 5B and synthon E from the pool of possibilities. In our ternary design we exploited these robust chemical features and a 1:1 solution of QUE and 44BP in iPrOH solution was layered with a saturated toluene solution of 2,2′-bis-thiophene (22TP) so that liquid diffusion takes place. The appearance of a 2:2:1 stoichiometric ternary solid with Conf 5B conformation and synthon E validated our anticipation and hints at the utility of the landscape idea in designing complex supramolecular architectures. We have shown shape and size mimicry of 22TP for 44BP in ternary solids earlier (Tothadi et al., 2011 ▸). Using this molecular mimicry as a guide leads to a well ordered QUE:44BP:22TP stoichiometric ternary solid (Fig. 7 ▸), which is not a solid solution. Tetrathiofulvalene (TTF) as a template highlights an efficient selection of one of four possible synthons, namely synthon B that is associated with Conf 6B, from the corresponding libraries in solution (Fig. 8 ▸). Both this conformation and this synthon could be termed virtual in the context of this QUE:44BP landscape because they were not observed in this system until the isolation of this particular solid. We extended this ternary design argument with the QUE:DPE-I cocrystal landscape. This exercise highlights recurring molecular conformations like Conf 5B, Conf 6B and Conf 7B in several crystal forms during landscape exploration. The shape–size mimicry of 22TP with 44BP once again acts as a guide for the selection of Conf 5B and synthon E in the prenucleation events. These precise selections in supramolecular synthesis facilitate the emergence of a porous molecular arrangement and helps to isolate a QUE:DPE-I:22TP ternary solid. Unlike the QUE:44BP:22TP ternary solid, the ‘longer’ coformer provides a larger porous cavity in the QUE:DPE-I binary cocrystal that can efficiently accommodate a 22TP molecule that has both orientational and positional disorder in the pocket (Fig. 7 ▸). Like the TTF template in QUE:44BP, pyrene (PYR) plays a characteristic role in QUE:DPE-I for the amplification of ‘virtual’ Conf 6B and synthon B chemical features in the ternary solid (Fig. 8 ▸).


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

Dubey R, Desiraju GR - IUCrJ (2015)

Ternary design strategy. TTF (top) and PYR (lower) as template molecules in QUE:44BP and QUE:DPE-I cocrystals. These crystal structures also highlight tghe virtual selection of Conf 6B and synthon B.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig8: Ternary design strategy. TTF (top) and PYR (lower) as template molecules in QUE:44BP and QUE:DPE-I cocrystals. These crystal structures also highlight tghe virtual selection of Conf 6B and synthon B.
Mentions: The design strategy for ternary solids depends upon the QUE:44BP landscape in which there are consistent appearances of Conf 5B and synthon E from the pool of possibilities. In our ternary design we exploited these robust chemical features and a 1:1 solution of QUE and 44BP in iPrOH solution was layered with a saturated toluene solution of 2,2′-bis-thiophene (22TP) so that liquid diffusion takes place. The appearance of a 2:2:1 stoichiometric ternary solid with Conf 5B conformation and synthon E validated our anticipation and hints at the utility of the landscape idea in designing complex supramolecular architectures. We have shown shape and size mimicry of 22TP for 44BP in ternary solids earlier (Tothadi et al., 2011 ▸). Using this molecular mimicry as a guide leads to a well ordered QUE:44BP:22TP stoichiometric ternary solid (Fig. 7 ▸), which is not a solid solution. Tetrathiofulvalene (TTF) as a template highlights an efficient selection of one of four possible synthons, namely synthon B that is associated with Conf 6B, from the corresponding libraries in solution (Fig. 8 ▸). Both this conformation and this synthon could be termed virtual in the context of this QUE:44BP landscape because they were not observed in this system until the isolation of this particular solid. We extended this ternary design argument with the QUE:DPE-I cocrystal landscape. This exercise highlights recurring molecular conformations like Conf 5B, Conf 6B and Conf 7B in several crystal forms during landscape exploration. The shape–size mimicry of 22TP with 44BP once again acts as a guide for the selection of Conf 5B and synthon E in the prenucleation events. These precise selections in supramolecular synthesis facilitate the emergence of a porous molecular arrangement and helps to isolate a QUE:DPE-I:22TP ternary solid. Unlike the QUE:44BP:22TP ternary solid, the ‘longer’ coformer provides a larger porous cavity in the QUE:DPE-I binary cocrystal that can efficiently accommodate a 22TP molecule that has both orientational and positional disorder in the pocket (Fig. 7 ▸). Like the TTF template in QUE:44BP, pyrene (PYR) plays a characteristic role in QUE:DPE-I for the amplification of ‘virtual’ Conf 6B and synthon B chemical features in the ternary solid (Fig. 8 ▸).

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