Understanding and Designing Tailor-Made Additives for Controlling Nucleation: Case Study of <i>p</i>-Aminobenzoic Acid Crystallizing from Ethanolic Solutions

A workflow for tailor-made additive screening and crystallization control using a combination of molecular modeling experimental techniques is presented. The impact seven structurally analogous additives, the majority which contain carboxylic acid group, on nucleation α-para-aminobenzoic assessed. Intermolecular grid search used to determine dimer interaction energies. Of these, three additives are found form stronger group interactions with compound. Solvation energy calculations demonstrate stability these dimers in solution. Subsequent intermolecular assessment demonstrates an ability one interfere preassembly route nucleation, charge distributions providing insight into this effect. Polythermal confirms effectiveness inhibit nucleation. Interestingly, mechanism change from instantaneous progressive absence presence solution, respectively, together increase effective interfacial tension.