Department of Chemistry and Biochemistry, Old Dominion University, 4402 Elkhorn Ave., Norfolk, VA 23529, USA.
Department of Chemistry, University of Virginia, Charlottesville, VA 22904, USA.
Acta Crystallogr C Struct Chem. 2021 Sep 1;77(Pt 9):566-576. doi: 10.1107/S2053229621008275. Epub 2021 Aug 25.
Quinine (an antimalarial) and aspirin (a nonsteroidal anti-inflammatory drug) were combined into a new drug-drug salt, quininium aspirinate, CHNO·CHO, 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.
奎宁（一种抗疟药）和阿司匹林（一种非甾体抗炎药）通过使用化学计量的反应物在 1:1 摩尔比，以及水、乙醇、甲苯或庚烷作为添加剂，在液体辅助研磨中组合成一种新的药物-药物盐，奎宁基阿司匹林，CHNO·CHO。使用乙醇作为添加剂制备的机械化学产物的四氢呋喃（THF）溶液导致通过机械化学获得的相同材料的单晶，该单晶用于在 100 K 下进行晶体结构测定。粉末 X 射线衍射排除了在 100-295 K 间隔内的结晶相转变。纯机械处理（在研钵和研杵中，或在 20 或 30 Hz 研磨频率下的球磨机中）产生无定形相，如粉末 X 射线衍射所示；然而，傅里叶变换红外（FT-IR）光谱明确表明发生了机械化学反应。在 10 和 15 Hz 下纯研磨反应物导致反应不完全。热重分析和差示扫描量热法表明，无定形和结晶机械化学产物在熔化前形成玻璃/过冷液体，并且在冷却时不会再结晶。然而，通过纯研磨获得的无定形材料在储存时结晶为报告的盐。本文报道了奎宁基阿司匹林的机械化学合成、晶体结构分析、Hirshfeld 表面、粉末 X 射线衍射、热重分析、差示扫描量热法、FT-IR 光谱和水溶液溶解度。
