Ferguson Michael, Moyano M Silvina, Tribello Gareth A, Crawford Deborah E, Bringa Eduardo M, James Stuart L, Kohanoff Jorge, Del Pópolo Mario G
CONICET , Facultad de Ciencias Exactas y Naturales , Universidad Nacional de Cuyo , Mendoza , Argentina . Email:
School of Chemistry and Chemical Engineering , Queen's University Belfast , Belfast , Northern Ireland , UK . Email:
Chem Sci. 2019 Jan 23;10(10):2924-2929. doi: 10.1039/c8sc04971h. eCollection 2019 Mar 14.
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.
尽管无溶剂机械化学合成的重要性不断提高，但此类反应过程中发生的分子尺度过程在很大程度上仍未得到充分表征。在此，我们应用计算模型来模拟阿司匹林和美洛昔康晶体颗粒在各种条件下的压痕，以模拟它们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。研究发现，尽管反应物具有固体晶体性质且溶剂很少或不存在，但即使在相对低能量的碰撞过程中，分子水平上的混合也很容易发生。当随后将压痕晶体拉开时，可以观察到由反应物分子混合物形成的连接颈，这表明反应材料具有类似塑性的行为。总体而言，这项工作揭示了一些惊人的新见解，包括：（i）在无溶剂条件下晶体相对容易混合；（ii）局部温度没有明显升高；（iii）反应晶体的接触区域和颈部出现局部非晶化；（iv）在反应的早期阶段，少量溶剂的影响相对较小，这表明它们对反应的加速作用可能在后期阶段发挥。
