This study aimed to gain insight into cocrystal interactions through solid-state characterization and theoretical computation. We formulated four novel cocrystalline phases of antipyrine (AN) and aminophenazone (AM) with coformer fumaric acid (FA) and saccharin (SA), respectively. The cocrystals were prepared by solvent-assisted grinding and slow evaporation. Solid-state characterization was conducted through differential scanning calorimetry, powder X-ray diffraction, and single-crystal X-ray diffraction. Crystal structure analysis showed that AN and SA created a 1:1 cocrystal. However, the proton transfer reaction caused AM and SA to produce a 1:1 salt through charge-assisted strong hydrogen-bonding interactions between the quaternary ammonium cationic group and the carbonyl group. As expected, the presence of two carboxyl groups with the same property in FA indicated that AN and AM formed 2:1 cocrystals with FA. Density functional calculations indicated that H bond interactions in cocrystals mainly involved pairwise interactions in the global maxima and minima sites on molecular electrostatic potential surfaces, but this rule did not apply to the salt. In addition, the H-bond interaction was further explained by using the highest occupied molecular orbital, lowest unoccupied molecular orbital, Hirshfeld surface, and mutual penetration distances of the van der Waals surface.

中文翻译：

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共晶体相互作用的结构和计算见解：安替比林和氨基苯乙酮共晶体的一个案例。

这项研究旨在通过固态表征和理论计算来深入了解共晶相互作用。我们分别用辅酶富马酸（FA）和糖精（SA）配制了安替比林（AN）和氨酚（AM）的四个新的共晶相。通过溶剂辅助研磨和缓慢蒸发制备共晶体。通过差示扫描量热法，粉末X射线衍射和单晶X射线衍射进行固态表征。晶体结构分析表明，AN和SA生成了1：1的共晶体。然而，质子转移反应通过季铵阳离子基团和羰基之间的电荷辅助强氢键相互作用，导致AM和SA产生1：1的盐。不出所料 FA中两个具有相同性质的羧基的存在表明AN和AM与FA形成2：1共晶。密度泛函计算表明，共晶中的H键相互作用主要涉及分子电势表面上全局最大值和最小值位置的成对相互作用，但该规则不适用于盐。此外，通过使用最高占据分子轨道，最低未占据分子轨道，Hirshfeld表面以及范德华表面的相互穿透距离进一步解释了H键相互作用。密度泛函计算表明，共晶中的H键相互作用主要涉及分子电势表面上全局最大值和最小值位置的成对相互作用，但该规则不适用于盐。此外，通过使用最高占据分子轨道，最低未占据分子轨道，Hirshfeld表面以及范德华表面的相互穿透距离进一步解释了H键相互作用。密度泛函计算表明，共晶中的H键相互作用主要涉及分子电势表面上全局最大值和最小值位置的成对相互作用，但该规则不适用于盐。此外，通过使用最高占据分子轨道，最低未占据分子轨道，Hirshfeld表面以及范德华表面的相互穿透距离进一步解释了H键相互作用。