Understanding and Designing Tailor-Made Additives for Controlling Nucleation: Case Study of pAminobenzoic Acid Crystallizing from Ethanolic Solutions [component]

A workflow for tailor-made additive screening and crystallisation control using a combination of molecular modelling and experimental techniques is presented. The impact of seven structurally analogous additives, the majority of which containing a carboxylic acid group, on the nucleation of alpha-para-aminobenzoic acid is assessed. Intermolecular grid-search modelling is used to determine dimer interaction energies. Of these, three tailor-made additives are found to form stronger carboxylic
more » ... p dimer interactions with the compound. Solvation energy calculations demonstrate the stability of these dimers in solution. Subsequent intermolecular interaction assessment demonstrates an ability of one of the tailor-made additives to interfere with the molecular preassembly route to nucleation, with molecular charge distributions providing an insight into this effect. Polythermal crystallisation experimental screening confirms the effectiveness of these tailor-made additives to inhibit nucleation. Interestingly, the nucleation mechanism is found to change from instantaneous to progressive nucleation in the absence and presence of the tailor-made additives in solution, respectively, together with an increase in the effective interfacial tension. It includes: pABA crystallisation background science, grid optimization, intermolecular interaction energies and contributions, dimer interaction geometries, dimer solvation and pABA interaction energies, TMAs within pABA crystal structure, statistical T-test, TMA screen MSZWs, pABA optical micrographs, crystallisation and dissolution temperatures, crystallisability and van't Hoff analysis and nucleation kinetic analysis.
doi:10.1021/acs.cgd.0c01209.s001 fatcat:wzndpzafmzbm7gmoq2egn7jg5q