Influence of Chemical Functionality on the Rate of Polymer-Induced Heteronucleation.

Polymer-induced heteronucleation can dramatically increase the nucleation rate of pharmaceuticals. However, directly comparing the heteronucleation rates of different polymer functionalities is often convoluted with changing physical or structural aspects of heteronuclei. Here, we report a methodology for comparing nucleation efficiencies of different functionalities on polymer heteronuclei of uniform topology with the goal of identifying those functionalities that best accelerate nucleation of a model pharmaceutical. It was found that the previously employed design for additives to speed acetaminophen crystallization underperforms a modified framework that accounts for the effect of competitive solvent binding. These findings are informed by a survey of interactions from the CSD and not only serve to aid in the controlled crystallization of pharmaceuticals, but also provide insight into the mechanism of heteronucleation.