德国Avant-garde Materials Simulation公司Marcus A. Neumann课题组近日取得一项新成果。经过不懈努力，他们的最新研究预测了在现实世界的条件下晶体形式的稳定性。相关论文发表在2023年11月8日出版的《自然》杂志上。

在该研究中，课题组重新定义了目前的技术水平，主要是通过提高自由能计算的准确性，构建固体-固体自由能差异的可靠实验基准，量化计算自由能的统计误差，并将不同化学计量的水合物晶体结构和无水晶体结构放在相同的能量图上（具有明确的误差范围），作出其对温度和相对湿度的函数。对于工业相关化合物，计算得到的自由能标准误差为1–2 kJ mol⁻¹，并且将具有不同水合物化学计量的晶体结构放置在同一能量图上的方法，可以推广到其他多组分体系，包括溶剂化物。

研究人员表示，这些贡献缩小了实验人员的需求与现代计算工具的能力之间的差距，将晶体结构预测转变为更可靠和可操作的程序，可以结合实验证据来指导晶体形态选择和建立控制。通过建立固体自由能差的实验基准，量化计算自由能的统计误差，并将水合物和非水合物晶体结构置于相同的能量图中，可以提高自由能计算的准确性。

据悉，分子晶体的物理化学性质，如溶解度、稳定性、致密性、熔融行为和生物利用度，取决于它们的晶体形态。计算化的晶体形式的选择最近越来越接近实现，因为精确和负担得起的自由能计算在发展。

附：英文原文

Title: Predicting crystal form stability under real-world conditions

Author: Firaha, Dzmitry, Liu, Yifei Michelle, van de Streek, Jacco, Sasikumar, Kiran, Dietrich, Hanno, Helfferich, Julian, Aerts, Luc, Braun, Doris E., Broo, Anders, DiPasquale, Antonio G., Lee, Alfred Y., Le Meur, Sarah, Nilsson Lill, Sten O., Lunsmann, Walter J., Mattei, Alessandra, Muglia, Pierandrea, Putra, Okky Dwichandra, Raoui, Mohamed, Reutzel-Edens, Susan M., Rome, Sandrine, Sheikh, Ahmad Y., Tkatchenko, Alexandre, Woollam, Grahame R., Neumann, Marcus A.

Issue&Volume: 2023-11-08

Abstract: The physicochemical properties of molecular crystals, such as solubility, stability, compactability, melting behaviour and bioavailability, depend on their crystal form1. In silico crystal form selection has recently come much closer to realization because of the development of accurate and affordable free-energy calculations2–4. Here we redefine the state of the art, primarily by improving the accuracy of free-energy calculations, constructing a reliable experimental benchmark for solid–solid free-energy differences, quantifying statistical errors for the computed free energies and placing both hydrate crystal structures of different stoichiometries and anhydrate crystal structures on the same energy landscape, with defined error bars, as a function of temperature and relative humidity. The calculated free energies have standard errors of 1–2 kJ mol−1 for industrially relevant compounds, and the method to place crystal structures with different hydrate stoichiometries on the same energy landscape can be extended to other multi-component systems, including solvates. These contributions reduce the gap between the needs of the experimentalist and the capabilities of modern computational tools, transforming crystal structure prediction into a more reliable and actionable procedure that can be used in combination with experimental evidence to direct crystal form selection and establish control. Accuracy of free-energy calculations can be improved by constructing an experimental benchmark for solid–solid free-energy differences, quantifying statistical errors for the computed free energies and placing both hydrate and anhydrate crystal structures on the same energy landscape.

DOI: 10.1038/s41586-023-06587-3

Source: https://www.nature.com/articles/s41586-023-06587-3