Adsmond D A, Grant D J
Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Weaver-Densford Hall, 308 Harvard Street S.E., Minneapolis, Minnesota 55455-0343, USA.
J Pharm Sci. 2001 Dec;90(12):2058-77. doi: 10.1002/jps.1157.
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.
利用图集合表示法解析并描述了39种磺胺晶体结构中的氢键连接性。所观察到的氢键连接性用于获取有关相关磺胺分子特定供体和受体原子的氢键偏好信息。酰胺质子对与脒氮和共晶客体形成氢键表现出更大的偏好，而氨基质子对与磺酰氧形成氢键表现出更大的偏好，形成了唯一占主导地位的氢键模式，即具有八个原子重复单元的链。在磺胺二甲嘧啶的五个共晶结构中观察到了脒基与客体羧基之间的优先氢键作用。磺胺恶唑呈现出一种在任何其他结构中都未见过的构象和氢键基序。磺胺嘧啶和磺胺二甲嘧啶仅相差一个甲基，但在氢键模式上没有相似性，而具有空间相似但化学不同杂环的磺胺甲氧嗪和磺胺甲异恶唑在氢键模式上表现出惊人的相似性。磺胺甲氧嗪、磺胺甲异恶唑和磺胺恶唑在多晶型物之间的氢键模式也有很大差异。通过揭示密切相关的有机晶体结构中氢键模式的细节，这样的研究有可能在药物固体的晶体结构之间提供预测能力。
