Kubicki M, Kindopp T W, Capparelli M V, Codding P W
Department of Chemistry, University of Calgary, Alberta, Canada.
Acta Crystallogr B. 1996 Jun 1;52 ( Pt 3):487-99. doi: 10.1107/s0108768195011773.
The crystal structures of five 1, 4-dihydro-2, 3-quinoxalinediones, antagonists of the NMDA modulatory glycine binding site on the excitary amino acid (EAA) receptor complex, have been determined: (I) 6, 7-dinitro-1, 4-dihydro-2, 3-quinoxalinedione (DNQX); (II) 5, 7-dinitro-1,4-dihydro-2, 3-quinoxalinedione (MNQX); (III) 6-nitro-1,4-dihydro-2, 3-quinoxalinedione hydrate; (IV) 6, 7-dichloro-1, 4-dihydro-2, 3-quinoxalinedione; (V) 5, 7-dichloro-I, 4-dihydro-2, 3-quinoxalinedione dimethylformamide. The crystal structure of the most active compound (II) contains a unique intramolecular N--H...O(NO2) hydrogen bond, which may be important for activity, as semiempirical calculations show that this bond is stable over a wide range of dihedral angles between the planes of the molecule and of the nitro group. In the other compounds the intermolecular hydrogen bonds connect molecules into three-dimensional networks. In compounds (I), (III) and (IV) head-to-tail pi-stacking is found between molecules connected by a center of symmetry. The geometries of the hydrogen-bonded -NH-C = O fragments show evidence of pi-cooperativity or resonance-assisted hydrogen bonding. Graph-set analysis of the hydrogen-bond patterns of quinoxalinedione derivatives shows a tendency to form two types of hydrogen-bonding motifs: a centrosymmetric dimeric ring and an infinite chain. Even though this pattern may be modified by the presence of additional hydrogen-bond acceptors and/or donors, as well as by solvent molecules, general similarities have been found. Comparison of all quinoxalinedione structures suggests that the hydrogen-bonding pattern necessary for the biological activity at the glycine binding site contains one donor and two acceptors.
已测定了五种1,4 - 二氢 - 2,3 - 喹喔啉二酮的晶体结构，它们是兴奋性氨基酸（EAA）受体复合物上NMDA调节性甘氨酸结合位点的拮抗剂：（I）6,7 - 二硝基 - 1,4 - 二氢 - 2,3 - 喹喔啉二酮（DNQX）；（II）5,7 - 二硝基 - 1,4 - 二氢 - 2,3 - 喹喔啉二酮（MNQX）；（III）6 - 硝基 - 1,4 - 二氢 - 2,3 - 喹喔啉二酮水合物；（IV）6,7 - 二氯 - 1,4 - 二氢 - 2,3 - 喹喔啉二酮；（V）5,7 - 二氯 - 1,4 - 二氢 - 2,3 - 喹喔啉二酮二甲基甲酰胺。活性最高的化合物（II）的晶体结构包含一个独特的分子内N - H...O(NO₂)氢键，这可能对活性很重要，因为半经验计算表明，在分子平面与硝基平面之间的广泛二面角范围内，该键是稳定的。在其他化合物中，分子间氢键将分子连接成三维网络。在化合物（I）、（III）和（IV）中，通过对称中心连接的分子之间存在头对头的π - 堆积。氢键连接的 -NH - C = O片段的几何结构显示出π - 协同作用或共振辅助氢键的证据。喹喔啉二酮衍生物氢键模式的图集分析表明，倾向于形成两种类型的氢键基序：中心对称二聚环和无限链。尽管这种模式可能会因额外的氢键受体和/或供体以及溶剂分子的存在而改变，但已发现了一般相似性。所有喹喔啉二酮结构的比较表明，甘氨酸结合位点生物活性所需的氢键模式包含一个供体和两个受体。
