To further understand the relationship among molecular conformational flexibility, thermodynamics, nucleation, and the polymorphic outcomes, the homogeneous nucleation and heterogeneous nucleation from fast cooling crystallization, evaporative crystallization, antisolvent crystallization, and solution-mediated polymorphic transformation were studied, considering the effects of temperature, supersaturation, and solvent. The conformers can rapidly fluctuate in solution with either monomers solvated by solvent molecules or carboxylic acid dimers and stacked dimers. No links between conformational flexibility and polymorphic outcome were found from both the experiment results and DFT calculation, though conformational polymorphs were obtained during the crystallization of 4-hexyloxybenzoic acid (HOBA). The stability relationship of HOBA polymorphs was confirmed, and the desolvation process was found to play a vital role in the overall self-assembly during crystallization. Finally, a process-control chart to prepare different polymorphs of HOBA was drawn to summarize the polymorphic differences caused by conformation.

中文翻译：

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构象柔韧性和结晶性：以4-己氧基苯甲酸为例

为了进一步了解分子构象柔韧性，热力学，成核和多晶形结果之间的关系，考虑了温度的影响，研究了快速冷却结晶，蒸发结晶，反溶剂结晶和溶液介导的多晶型转变造成的均匀成核和不均匀成核。 ，过饱和度和溶剂。所述构象异构体可以在溶液中迅速地与被溶剂分子溶解的单体或羧酸二聚体和堆叠的二聚体一起波动。尽管在4-己氧基苯甲酸（HOBA）的结晶过程中获得了构象多晶型物，但是从实验结果和DFT计算中都没有发现构象柔性与多晶型结果之间的联系。证实了HOBA多晶型物的稳定性关系，并且发现去溶剂化过程在结晶过程中对整体自组装起着至关重要的作用。最后，绘制了制备HOBA不同多晶型物的过程控制图，以总结由构象引起的多态性差异。