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. (C) 2001 Wiley-Liss, Inc, and the American Pharmaceutical Association J Pharm Sci 90:2058-2077, 2001.