Mechanochemical synthesis insights and solid-state characterization of quininium aspirinate, a glass-forming drug-drug salt.
Mechanochemical synthesis insights and solid-state characterization of quininium aspirinate, a glass-forming drug-drug salt.
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阿司匹林奎宁（一种玻璃形成药物-药物盐）的机械化学合成见解和固态表征。
DOI：
10.1107/s2053229621008275
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Pagola,Silvina
中科院分区：
文献类型：
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作者：
Harris,Nehemiah;Benedict,Jubilee;Dickie,DianeA;Pagola,Silvina
奎宁（一种抗疟药）和阿司匹林（一种非甾体抗炎药）通过液体辅助研磨，以化学计量量的反应物按1:1的摩尔比混合成一种新的药物盐——阿斯匹林奎宁，C20H25N2O2+·C9H7O4−，水、乙醚、甲苯或庚烷作为添加剂。以四氢呋喃（THF）溶液为添加剂制备的机械化学产物，通过机械化学得到了相同材料的单晶，并在100 K下进行了晶体结构测定。粉末x射线衍射排除了100-295 K区间的晶体相变。整齐的机械处理（在研钵和杵中，或在20或30赫兹磨粉频率的球磨机中）产生非晶相，如粉末x射线衍射所示；然而，傅里叶变换红外光谱明确表明发生了机械化学反应。在10赫兹和15赫兹的条件下研磨反应物会导致反应不完全。热重法和差示扫描量热法表明，非晶和结晶的机械化学产物在熔化前形成玻璃/过冷液体，冷却后不再结晶。然而，通过整齐研磨获得的非晶态材料在储存到盐中时结晶。本文报道了阿斯匹林醌的机械化学合成、晶体结构分析、赫什菲尔德表面、粉末x射线衍射、热重法、差示扫描量热法、傅里叶红外光谱和水溶性。
Quinine (an antimalarial) and aspirin (a nonsteroidal anti-inflammatory drug) were combined into a new drug–drug salt, quininium aspirinate, C20H25N2O2+·C9H7O4−, by liquid-assisted grinding using stoichiometric amounts of the reactants in a 1:1 molar ratio, and water, EtOH, toluene, or heptane as additives. A tetrahydrofuran (THF) solution of the mechanochemical product prepared using EtOH as additive led to a single crystal of the same material obtained by mechanochemistry, which was used for crystal structure determination at 100 K. Powder X-ray diffraction ruled out crystallographic phase transitions in the 100–295 K interval. Neat mechanical treatment (in a mortar and pestle, or in a ball mill at 20 or 30 Hz milling frequencies) gave rise to an amorphous phase, as shown by powder X-ray diffraction; however, FT–IR spectroscopy unambiguously indicates that a mechanochemical reaction has occurred. Neat milling the reactants at 10 and 15 Hz led to incomplete reactions. Thermogravimetry and differential scanning calorimetry indicate that the amorphous and crystalline mechanochemical products form glasses/supercooled liquids before melting, and do not recrystallize upon cooling. However, the amorphous material obtained by neat grinding crystallizes upon storage into the salt reported. The mechanochemical synthesis, crystal structure analysis, Hirshfeld surfaces, powder X-ray diffraction, thermogravimetry, differential scanning calorimetry, FT–IR spectroscopy, and aqueous solubility of quininium aspirinate are herein reported.