Insights into mechanochemical reactions at the molecular level: simulated indentations of aspirin and meloxicam crystals
Insights into mechanochemical reactions at the molecular level: simulated indentations of aspirin and meloxicam crystals
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DOI：
10.1039/c8sc04971h
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发表时间：
2019-03-14
期刊：
影响因子：
8.4
通讯作者：
Del Popolo, Mario G.
中科院分区：
文献类型：
--
作者：
Ferguson, Michael;Silvina Moyano, M.;Del Popolo, Mario G.
虽然无溶剂机械化学合成继续获得越来越大的重要性，在这种反应过程中发生的分子尺度的过程仍然在很大程度上未被表征。在这里，我们应用计算模型，以各种条件下的阿司匹林和美洛昔康的晶体颗粒之间的压痕，以模拟其机械化学共结晶反应的早期阶段。该研究还扩展到少量溶剂存在的影响。人们发现，尽管反应物具有固体结晶性质并且存在很少或不存在溶剂，但即使在相对低能量的碰撞期间，也很容易在分子水平上发生混合。当锯齿状晶体随后被拉开时，观察到由反应物分子的混合物形成的连接颈部，这表明反应材料的塑料样行为。总的来说，这项工作揭示了一些引人注目的新见解，包括（i）在无溶剂条件下晶体的混合相对容易，（ii）没有明显的局部温度升高，（iii）在反应晶体的接触区域和颈部局部无定形化，以及（iv）少量溶剂在反应的早期阶段具有相对较小的影响，这表明它们对反应的加速作用可能在后期发挥。
Although solvent-free mechanochemical synthesis continues to gain ever greater importance, the molecular scale processes that occur during such reactions remain largely uncharacterised. Here, we apply computational modelling to indentations between particles of crystals of aspirin and meloxicam under a variety of conditions to mimic the early stages of their mechanochemical cocrystallisation reaction. The study also extends to the effects of the presence of small amounts of solvent. It is found that, despite the solid crystalline nature of the reactants and the presence of little or no solvent, mixing occurs readily at the molecular level even during relatively low-energy collisions. When indented crystals are subsequently drawn apart, a connective neck formed by a mixture of the reactant molecules is observed, suggesting plastic-like behaviour of the reacting materials. Overall the work reveals some striking new insights including (i) relatively facile mixing of crystals under solvent-free conditions, (ii) no appreciable local temperature increases, (iii) localised amorphisation at the contact region and neck of the reacting crystals, and (iv) small amounts of solvent have relatively little effect during this early stage of the reaction, suggesting that their accelerating effect on the reaction may be exerted at later stages.