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Modularity and three-dimensional isostructurality of novel synthons in sulfonamide-lactam cocrystals.

Bolla G, Mittapalli S, Nangia A - IUCrJ (2015)

Bottom Line: These heterosynthons of the cocrystals observed in this study are compared with the N-H⋯O dimer R 2 (2)(8) ring and C(4) chain motifs of the individual sulfonamide structures.One-dimensional, two-dimensional and three-dimensional isostructurality in crystal structures is associated with isosynthons and due to their recurrence, novel heterosynthons for sulfonamide cocrystals are added to the crystal engineer's toolkit.With the predominance of sulfa drugs in medicine, these new synthons provide rational strategies for the design of binary and potentially ternary cocrystals of sulfonamides.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Chemistry, University of Hyderabad , Prof. C. R. Rao Road, Central University PO, Hyderabad, 500 046, India.

ABSTRACT
The design of novel supramolecular synthons for functional groups relevant to drugs is an essential prerequisite for applying crystal engineering in the development of novel pharmaceutical cocrystals. It has been convincingly shown over the past decade that molecular level control and modulation can influence the physicochemical properties of drug cocrystals. Whereas considerable advances have been reported on the design of cocrystals for carboxylic acids and carboxamide functional groups, the sulfonamide group, which is a cornerstone of sulfa drugs, is relatively unexplored for reproducible heterosynthon-directed crystal engineering. The occurrence of synthons and isostructurality in sulfonamide-lactam cocrystals (SO2NH2⋯CONH hydrogen bonding) is analyzed to define a strategy for amide-type GRAS (generally recognized as safe) coformers with sulfonamides. Three types of supramolecular synthons are identified for the N-H donor of sulfonamide hydrogen bonding to the C=O acceptor of amide. Synthon 1: catemer synthon C 2 (1)(4) chain motif, synthon 2: dimer-cyclic ring synthon R 2 (2)(8)R 4 (2)(8) motifs, and synthon 3: dimer-catemer synthon of R 2 (2)(8)C 1 (1)(4)D notation. These heterosynthons of the cocrystals observed in this study are compared with the N-H⋯O dimer R 2 (2)(8) ring and C(4) chain motifs of the individual sulfonamide structures. The X-ray crystal structures of sulfonamide-lactam cocrystals exhibit interesting isostructurality trends with the same synthon being present. One-dimensional, two-dimensional and three-dimensional isostructurality in crystal structures is associated with isosynthons and due to their recurrence, novel heterosynthons for sulfonamide cocrystals are added to the crystal engineer's toolkit. With the predominance of sulfa drugs in medicine, these new synthons provide rational strategies for the design of binary and potentially ternary cocrystals of sulfonamides.

No MeSH data available.


Related in: MedlinePlus

Dimer–catemer synthon 3 in cocrystals 2ClBSA–VLM, 2ClBSA–CPR, OTSA–VLM, PTSA–VLM and two-dimensional hydrogen bond motifs. Two-dimensional packing diagrams are drawn with the asymmetric unit showing benzene sulfonamides (in green) and lactams (in blue) (VLM, CPR).
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fig6: Dimer–catemer synthon 3 in cocrystals 2ClBSA–VLM, 2ClBSA–CPR, OTSA–VLM, PTSA–VLM and two-dimensional hydrogen bond motifs. Two-dimensional packing diagrams are drawn with the asymmetric unit showing benzene sulfonamides (in green) and lactams (in blue) (VLM, CPR).

Mentions: Equimolar quantities of the components were ground and crystallized from EtOAc to give single crystals which were solved in the monoclinic space group P21/c. Catemer chains connect glide-related 2ClBSA molecules that assemble via homodimers of VLM through N—H⋯O (N1—H1A⋯O3 = 2.03 Å, ∠169°) hydrogen bonds in synthon 3, or dimer–catemer synthon R22(8)C11(4)D (Figs. 6 ▸a and b). In this synthon the coformer dimers are sandwiched between sulfonamide catemer chains. Halogen bonding (Cl⋯O, Cl⋯N) provides auxiliary support to the structure (Metrangolo et al., 2005 ▸, 2008 ▸; Saha & Nangia, 2007 ▸; Desiraju, 1989 ▸; Mukherjee et al., 2014 ▸). The catemer chains of 2ClBSA extend along the c-axis and homodimers of VLM connect adjacent chains of sulfonamides via C—H⋯O interactions to make two-dimensional stacks in the ab-plane (Fig. 6 ▸c).


Modularity and three-dimensional isostructurality of novel synthons in sulfonamide-lactam cocrystals.

Bolla G, Mittapalli S, Nangia A - IUCrJ (2015)

Dimer–catemer synthon 3 in cocrystals 2ClBSA–VLM, 2ClBSA–CPR, OTSA–VLM, PTSA–VLM and two-dimensional hydrogen bond motifs. Two-dimensional packing diagrams are drawn with the asymmetric unit showing benzene sulfonamides (in green) and lactams (in blue) (VLM, CPR).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4491311&req=5

fig6: Dimer–catemer synthon 3 in cocrystals 2ClBSA–VLM, 2ClBSA–CPR, OTSA–VLM, PTSA–VLM and two-dimensional hydrogen bond motifs. Two-dimensional packing diagrams are drawn with the asymmetric unit showing benzene sulfonamides (in green) and lactams (in blue) (VLM, CPR).
Mentions: Equimolar quantities of the components were ground and crystallized from EtOAc to give single crystals which were solved in the monoclinic space group P21/c. Catemer chains connect glide-related 2ClBSA molecules that assemble via homodimers of VLM through N—H⋯O (N1—H1A⋯O3 = 2.03 Å, ∠169°) hydrogen bonds in synthon 3, or dimer–catemer synthon R22(8)C11(4)D (Figs. 6 ▸a and b). In this synthon the coformer dimers are sandwiched between sulfonamide catemer chains. Halogen bonding (Cl⋯O, Cl⋯N) provides auxiliary support to the structure (Metrangolo et al., 2005 ▸, 2008 ▸; Saha & Nangia, 2007 ▸; Desiraju, 1989 ▸; Mukherjee et al., 2014 ▸). The catemer chains of 2ClBSA extend along the c-axis and homodimers of VLM connect adjacent chains of sulfonamides via C—H⋯O interactions to make two-dimensional stacks in the ab-plane (Fig. 6 ▸c).

Bottom Line: These heterosynthons of the cocrystals observed in this study are compared with the N-H⋯O dimer R 2 (2)(8) ring and C(4) chain motifs of the individual sulfonamide structures.One-dimensional, two-dimensional and three-dimensional isostructurality in crystal structures is associated with isosynthons and due to their recurrence, novel heterosynthons for sulfonamide cocrystals are added to the crystal engineer's toolkit.With the predominance of sulfa drugs in medicine, these new synthons provide rational strategies for the design of binary and potentially ternary cocrystals of sulfonamides.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Chemistry, University of Hyderabad , Prof. C. R. Rao Road, Central University PO, Hyderabad, 500 046, India.

ABSTRACT
The design of novel supramolecular synthons for functional groups relevant to drugs is an essential prerequisite for applying crystal engineering in the development of novel pharmaceutical cocrystals. It has been convincingly shown over the past decade that molecular level control and modulation can influence the physicochemical properties of drug cocrystals. Whereas considerable advances have been reported on the design of cocrystals for carboxylic acids and carboxamide functional groups, the sulfonamide group, which is a cornerstone of sulfa drugs, is relatively unexplored for reproducible heterosynthon-directed crystal engineering. The occurrence of synthons and isostructurality in sulfonamide-lactam cocrystals (SO2NH2⋯CONH hydrogen bonding) is analyzed to define a strategy for amide-type GRAS (generally recognized as safe) coformers with sulfonamides. Three types of supramolecular synthons are identified for the N-H donor of sulfonamide hydrogen bonding to the C=O acceptor of amide. Synthon 1: catemer synthon C 2 (1)(4) chain motif, synthon 2: dimer-cyclic ring synthon R 2 (2)(8)R 4 (2)(8) motifs, and synthon 3: dimer-catemer synthon of R 2 (2)(8)C 1 (1)(4)D notation. These heterosynthons of the cocrystals observed in this study are compared with the N-H⋯O dimer R 2 (2)(8) ring and C(4) chain motifs of the individual sulfonamide structures. The X-ray crystal structures of sulfonamide-lactam cocrystals exhibit interesting isostructurality trends with the same synthon being present. One-dimensional, two-dimensional and three-dimensional isostructurality in crystal structures is associated with isosynthons and due to their recurrence, novel heterosynthons for sulfonamide cocrystals are added to the crystal engineer's toolkit. With the predominance of sulfa drugs in medicine, these new synthons provide rational strategies for the design of binary and potentially ternary cocrystals of sulfonamides.

No MeSH data available.


Related in: MedlinePlus