Exploring the Multi-minima Behavior of Small Molecule Crystal Polymorphs at Finite Temperature
Exploring the Multi-minima Behavior of Small Molecule Crystal Polymorphs at Finite Temperature
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DOI：
10.1021/acs.cgd.9b00476
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发表时间：
2019-10-01
影响因子：
3.8
通讯作者：
Shirts, Michael R.
中科院分区：
文献类型：
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作者：
Dybeck, Eric C.;McMahon, David P.;Shirts, Michael R.
预测的环境温度下有机小分子的晶体结构通常用单个能量最小化构型来表示。这一过程有效地将在环境温度下存在的构型集合折叠成一个单一的代表性结构。如果晶体结构在环境温度系综中具有多个不同的晶格能量最小值，则这种简化可能会被打破。在这项工作中，我们通过在一定温度范围内取样晶体，然后快速淬火结构，探索了有限温度晶体盆地中多个极小值的存在。然后，我们观察每个晶体是否返回到原始的最小值或晶格能量景观的最小值集合。本研究中所检测的12个化合物中有8个具有至少一个具有多极小行为的多晶型。这些多极小期盆地对晶体结构预测研究具有重要意义，因此了解导致晶体结构具有多个极小期的因素非常重要。我们发现，在一般情况下，在一个晶盆中，对于较大和更有灵活性的化合物，更有可能存在多个极小值。我们发现，随着采样温度的升高，最小值的数目有增加的趋势，从相同的有限温度轨迹中发现的最小值的晶格能可以变化>2.0 kJ/mol。最后，我们证明了在一个单一的环境温度盆地中包含的晶格能量极小值可以在不对称单元中具有不同的空间群和分子数。总的来说，数据表明，许多实验晶体多晶态可能具有多极小值行为，并且最好用包含许多极小值的结构集合来描述，而不是用单个晶格能量极小值来描述。
The predicted ambient-temperature crystal structures of organic small molecules are often represented by a single energy-minimized configuration at 0 K. This procedure effectively collapses the ensemble of configurations that would be present at ambient temperature into a single representative structure. This simplification is likely to break down if the crystal structure has multiple different latticeenergy minima within the ambient-temperature ensemble. In this work, we explore the existence of multiple minima within finite-temperature crystal basins by sampling crystals at a range of temperatures followed by rapidly quenching the configurations. We then observe whether each crystal returns to the original minimum or to an ensemble of minima on the lattice-energy landscape. Eight of the twelve compounds examined in this work have at least one polymorph with multi-minima behavior. These multi-minima basins have implications for crystal structure prediction studies, and it is therefore important to understand the factors that lead a crystal structure to have multiple minima. We find that, in general, the existence of multiple minima within a crystal basin is more likely for the compounds that are larger and have more flexibility. We find that the number of minima found tends to increase with the sampling temperature, and the lattice energy of minima found from the same finite-temperature trajectory can vary by >2.0 kJ/mol. Finally, we show that the lattice-energy minima contained within a single ambient-temperature basin can have different space groups and numbers of molecules in the asymmetric unit. Overall, the data suggest that many experimental crystal polymorphs are likely to have multi-minima behavior and are best described by an ensemble of structures encompassing many minima rather than by a single lattice-energy minimum.