...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Crystal growth & design >Packing Interactions and Physicochemical Properties of Novel Multicomponent Crystal Forms of the Anti-Inflammatory Azelaic Acid Studied by X-ray and Solid-State NMR
【24h】

Packing Interactions and Physicochemical Properties of Novel Multicomponent Crystal Forms of the Anti-Inflammatory Azelaic Acid Studied by X-ray and Solid-State NMR

机译：X射线和固态NMR研究新型抗炎性壬二酸多组分晶型的堆积相互作用和理化性质

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The reactivity of the active pharmaceutical ingredient azelaic acid (AA) with carboxylic acid, alcohol, amine, and amide based co-formers was screened. Five new multicomponent crystal forms of AA were obtained by liquid assisted grinding and conventional solution methods. The obtained forms: (i) a co-crystal with 4,4'-bipyridine (AA:BIP, 1), (ii) an anhydrous and an hydrated molecular salt with piperazine (AA:PIP, 2 and 3), and (iii) two anhydrous molecular salts with morpholine (AA:MORPH, 4) and 1,4-diazobicyclo[2.2.2]octane (AA:DABCO, 5), were fully characterized by X-ray diffraction and solid-state (SS) NMR. In all new forms the carboxylic-carboxylic R-2(2)(8) homosynthon present in AA is broken, and NH2 center dot center dot center dot O-COOH or +NH2 center dot center dot center dot O-COO-hydrogen bonds (HBs) become the fundamental pillars in the new supramolecular arrangements. The X-ray structure of 4 exhibits a static disorder in the hydrogen atoms engaged in an HB between two COOH moieties of AA. Density functional theory geometry optimization of the hydrogen positions followed by GIPAW-DFT calculations of H-1 chemical shifts showed that such disordered atoms refer to O center dot center dot center dot H center dot center dot center dot O hydrogens, roughly equidistant from both proton acceptor and donor atoms. SSNMR detected unusually strong HBs associated with such disordered hydrogens through the presence of H-1 resonances shifted to very high frequencies (up to ca. 20.1 ppm). These results clearly show the advantageous use of both X-ray diffraction and SSNMR techniques for structural elucidation. We concluded that the hydrated piperazine salt 3 readily converted to 2 at ambient RH and that their thermal behavior is strongly determined by both the supramolecular arrangement and strength of HB network. Piperazine salt 2 presents an improved aqueous solubility bestowing a promising opportunity to avoid the use of alcoholic solutions in the final formulations.
机译：筛选了活性药物成分壬二酸（AA）与羧酸，醇，胺和酰胺基共形成物的反应性。通过液体辅助研磨和常规溶液方法获得了五种新的AA多晶形式。获得的形式：（i）与4,4'-联吡啶（AA：BIP，1）的共晶体，（ii）与哌嗪的无水和水合分子盐（AA：PIP，2和3），和（ iii）通过X射线衍射和固态（SS）充分表征了吗啉（AA：MORPH，4）和1,4-重氮二环[2.2.2]辛烷（AA：DABCO，5）的两种无水分子盐。核磁共振。在所有新形式中，AA中存在的羧基-羧基R-2（2）（8）同合成子被破坏，NH2中心点中心点中心点O-COOH或+ NH2中心点中心点中心点O-COO-氢键（HBs）成为新的超分子安排的基本支柱。 4的X射线结构在与AA的两个COOH部分之间的HB中所结合的氢原子中表现出静态无序。氢位置的密度泛函理论几何优化以及随后的H-1化学位移的GIPAW-DFT计算表明，这种无序原子是指O中心点中心点中心点H中心点中心点中心点O氢，与两个质子的距离大致相等受体和供体原子。 SSNMR通过H-1共振转移到非常高的频率（高达约20.1 ppm）检测到与这种无序氢相关的异常强的HBs。这些结果清楚地表明，X射线衍射和SSNMR技术都可用于结构阐明。我们得出的结论是，水合的哌嗪盐3在环境RH下很容易转化为2，它们的热行为强烈地取决于超分子排列和HB网络的强度。哌嗪盐2表现出改善的水溶性，这为避免在最终配方中使用酒精溶液提供了广阔的机会。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号