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Solid-State Form Screen of Cardiosulfa and Its Analogues.
MedLine Citation:
PMID:  23616361     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Cardiosulfa is a biologically active sulfonamide molecule that was recently shown to induce abnormal heart development in zebrafish embryos through activation of the aryl hydrocarbon receptor (AhR). The present report is a systematic study of solid-state forms of cardiosulfa and its biologically active analogues that belong to the N-(9-ethyl-9H-carbazol-3-yl)benzene sulfonamide skeleton. Cardiosulfa (molecule 1; R(1) =NO2 , R(2) =H, R(3) =CF3 ), molecule 2 (H, H, CF3 ), molecule 3 (CF3 , H, H), molecule 4 (NO2 , H, H), molecule 5 (H, CF3 , H), and molecule 6 (H, H, H) were synthesized and subjected to a polymorph search and solid-state form characterization by X-ray diffraction, differential scanning calorimetry (DSC), variable-temperature powder X-ray diffraction (VT-PXRD), FTIR, and solid-state (ss) NMR spectroscopy. Molecule 1 was obtained in a single-crystalline modification that is sustained by NH⋅⋅⋅π and CH⋅⋅⋅O interactions but devoid of strong intermolecular NH⋅⋅⋅O hydrogen bonds. Molecule 2 displayed a NH⋅⋅⋅O catemer C(4) chain in form I, whereas a second polymorph was characterized by PXRD. The dimorphs of molecule 3 contain NH⋅⋅⋅π and CH⋅⋅⋅O interactions but no NH⋅⋅⋅O bonds. Molecule 4 is trimorphic with NH⋅⋅⋅O catemer in form I, and NH⋅⋅⋅π and CH⋅⋅⋅O interactions in form II, and a third polymorph was characterized by PXRD. Both polymorphs of molecule 5 contain the NH⋅⋅⋅O catemer C(4) chain, whereas the sulfonamide NH⋅⋅⋅O dimer synthon R2 (2) (8) was observed in polymorphs of 6. Differences in the strong and weak hydrogen-bond motifs were correlated with the substituent groups, and the solubility and dissolution rates were correlated with the conformation in the crystal structure of 1-6. Higher solubility compounds, such as 2 (10.5 mg mL(-1) ) and 5 (4.4 mg mL(-1) ), adopt a twisted confirmation, whereas less-soluble 1 (0.9 mg mL(-1) ) is nearly planar. This study provides practical guides for functional-group modification of drug lead compounds for solubility optimization.
Authors:
S Sudalai Kumar; Soumendra Rana; Ashwini Nangia
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-4-24
Journal Detail:
Title:  Chemistry, an Asian journal     Volume:  -     ISSN:  1861-471X     ISO Abbreviation:  Chem Asian J     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-4-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101294643     Medline TA:  Chem Asian J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Affiliation:
School of Chemistry, University of Hyderabad, Central University PO, Prof. C. R. Rao Road, Gachibowli, Hyderabad 500 046 (India).
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