Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, Colorado 80309, USA.
Department of Chemical Engineering, University of Virginia, Charlottesville, Virginia 22904, USA.
J Chem Phys. 2018 Apr 14;148(14):144104. doi: 10.1063/1.5013273.
Many physical properties of small organic molecules are dependent on the current crystal packing, or polymorph, of the material, including bioavailability of pharmaceuticals, optical properties of dyes, and charge transport properties of semiconductors. Predicting the most stable crystalline form at a given temperature and pressure requires determining the crystalline form with the lowest relative Gibbs free energy. Effective computational prediction of the most stable polymorph could save significant time and effort in the design of novel molecular crystalline solids or predict their behavior under new conditions. In this study, we introduce a new approach using multistate reweighting to address the problem of determining solid-solid phase diagrams and apply this approach to the phase diagram of solid benzene. For this approach, we perform sampling at a selection of temperature and pressure states in the region of interest. We use multistate reweighting methods to determine the reduced free energy differences between T and P states within a given polymorph and validate this phase diagram using several measures. The relative stability of the polymorphs at the sampled states can be successively interpolated from these points to create the phase diagram by combining these reduced free energy differences with a reference Gibbs free energy difference between polymorphs. The method also allows for straightforward estimation of uncertainties in the phase boundary. We also find that when properly implemented, multistate reweighting for phase diagram determination scales better with the size of the system than previously estimated.
许多小分子的物理性质取决于物质当前的晶体堆积形式（即多晶型物），包括药物的生物利用度、染料的光学性质和半导体的电荷输运性质。预测给定温度和压力下最稳定的晶体形式需要确定具有最低相对吉布斯自由能的晶体形式。有效预测最稳定的多晶型物可以在设计新型分子晶体固体时节省大量时间和精力，或者预测它们在新条件下的行为。在这项研究中，我们引入了一种新的方法，使用多态重加权来解决确定固-固相图的问题，并将该方法应用于固体苯的相图。对于该方法，我们在感兴趣的区域内选择温度和压力状态进行采样。我们使用多态重加权方法来确定给定多晶型物内 T 和 P 状态之间的降低自由能差异，并使用几种措施验证该相图。可以通过将这些降低自由能差异与多晶型物之间的参考吉布斯自由能差异相结合，从这些点对采样状态下的多晶型物的相对稳定性进行连续插值，从而创建相图。该方法还允许直接估计相界的不确定性。我们还发现，当正确实施时，用于相图确定的多态重加权方法的系统大小的缩放效果优于以前的估计。
