成核作为结晶的初始阶段, 直接影响着晶体产品的结构、手性、纯度、晶型和粒径分布等性质。但由于成核具有随机性, 通过实验成核不仅耗时耗力而且很难洞悉分子间的相互作用。本文选择结构相似的对羟基苯甲酸乙酯(EP)、对羟基苯甲酸丙酯(PP)和对羟基苯甲酸丁酯(BP)为模型物质, 计算了EP、PP和BP在四种不同的有机溶剂(乙醇、乙酸乙酯、丙酮、乙腈)中单个溶质分子和单个溶剂分子的结合能。不论是EP、PP还是BP与各溶剂的相互作用大小都服从乙醇>乙酸乙酯>丙酮>乙腈。因此, 可以预测EP、PP和BP在乙醇中成核最慢, 在乙酸乙酯和丙酮中成核较慢, 在乙腈中成核最快。当溶剂相同的时候, EP最难成核, 其次是PP, BP容易成核, 预测的结果与实验结果一致。本研究证明利用溶质-溶剂(1∶1)模型可以预测成核的难易, 进而有利于筛选溶剂, 提高实验效率。

As the initial stage of crystallization, nucleation directly affects the structure, chirality, purity, crystal forms and particle size distribution of crystal products. However, due to the random nature of nucleation, experimental methods are not only time-consuming and laborious, but also difficult to understand the molecular interactions. In this paper, ethyl paraben (EP), propyl paraben (PP) and butyl paraben (BP) with similar structure were selected as model substances, and the binding energies of single solute and single solvent molecules of EP, PP and BP in four different organic solvents (ethanol, ethyl acetate, acetone, acetonitrile) were calculated. The interaction of EP, PP and BP with each solvent decreases in the following order: ethanol>ethyl acetate>acetone>acetonitrile. Therefore, it can be predicted that EP, PP and BP nucleate slowest in ethanol, slower in ethyl acetate and acetone, and fastest in acetonitrile. When the solvent is the same, EP is the most difficult to nucleate, followed by PP, and BP is easy to nucleate. The predicted results are consistent with the experimental results. This study proves that the solute-solvent (1∶1) model can predict the difficulty of nucleation, which is conducive to solvent screening and improve experimental efficiency.