Hydrogen bonding in sulfonamides.
The hydrogen-bond connectivity in 39 sulfonamide crystal structures has been deciphered and described using graph set notation. The hydrogen-bond connectivity observed is used to gain information on hydrogen-bond preferences of specific donor and acceptor atoms of related sulfonamide molecules. The amido protons show a greater preference for hydrogen bonding to amidine nitrogens and cocrystal guests, whereas the amino protons show a greater preference for hydrogen bonding to sulfonyl oxygens, forming the only dominant hydrogen-bond pattern, a chain with an eight atom repeat unit. Preferential hydrogen bonding between the amidine group and the guest carboxyl group was observed in five cocrystal structures of sulfamethazine. Sulfamoxole displays a conformation and a hydrogen-bond motif not seen in any other structures. Sulfamerazine and sulfamethazine, differing by a methyl group, show no similarity in hydrogen-bond pattern, whereas sulfamethoxydiazine and sulfamethoxymethazine, which have sterically similar but chemically different heterocycles, show a striking similarity in hydrogen-bond pattern. Sulfamethoxydiazine, sulfamethoxymethazine, and sulfamethoxazole also show a large variation in hydrogen-bond pattern between polymorphs. Studies such as this, by revealing details of hydrogen-bonding patterns in closely related organic crystal structures, can potentially provide predictive capability among the crystal structures of pharmaceutical solids.
Adsmond
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Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Weaver-Densford Hall, 308 Harvard Street S.E., Minneapolis, Minnesota 55455-0343, USA. adsmondd@ferris.edu
Grant
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D000465:Algorithms; D000577:Amides / Q000737:chemistry; D000578:Amidines / Q000737:chemistry; D000588:Amines / Q000737:chemistry; D000890:Anti-Infective Agents / Q000737:chemistry*; D003460:Crystallization; D019281:Dimerization; D006860:Hydrogen Bonding; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D013416:Sulfamerazine / Q000737:chemistry; D013418:Sulfamethazine / Q000737:chemistry; D013420:Sulfamethoxazole / Q000737:chemistry; D013449:Sulfonamides / Q000737:chemistry*
D000577:Amides; D000578:Amidines; D000588:Amines; D000890:Anti-Infective Agents; D013449:Sulfonamides; D013418:Sulfamethazine; D013420:Sulfamethoxazole; D013416:Sulfamerazine