Template design based on molecular and crystal structure similarity to regulate conformational polymorphism nucleation: the case of α,ω-alkanedicarboxylic acids

Template design on polymorph control, especially conformational polymorphs, is still in its infancy and the result of polymorph control is often accidental. A method of regulating the crystallization of conformational polymorphs based on the crystal structure similarity of templates and the target crystal form has been developed. Crystal structure similarity was considered to be able to introduce lattice matching (geometric term) with chemical interactions to regulate conformational polymorph nucleation. The method was successfully applied to induce the crystallization of DA7-II [HOOC-(CH2)(n-2)-COOH (diacids), named DAn, where n = 7, 9, 15, 17 and II represents the metastable polymorph] on the surface of DA15-II. An analogous two-dimensional plane - the (002) face of both DA15-II and DA7-II - was firstly predicted as the epitaxially attached face with similar lattice parameters and the strongest adsorption energy. The powder DA15-II template with the preferred orientation face in (002) presented much stronger inducing DA7-II ability than the template with other preferred orientation faces. The epitaxial growth of DA7-II on DA15-II through an identical (002) face was clearly observed and verified by the single-crystal inducing experiments. The molecular dynamics simulation results demonstrated that the strong interactions occurred between DA7 molecules and the (002) face of DA15-II. This method has been verified and further applied to the crystallization of DA7-II on the surface of DA17-II and DA9-II on the surface of DA15-II. This study developed a strategy based on structure similarity to regulate the conformational polymorph and verified the significant role of lattice matching and chemical effects on the design and preparation of templates.

Automated summary

Template design for polymorph control, particularly in the case of conformational polymorphs, is still relatively new and often happens accidentally. A method has been developed to regulate the crystallization of conformational polymorphs based on crystal structure similarity between templates and target crystal forms, showing success in inducing the crystallization of DA7-II on the surface of DA15-II. This study highlights the significant role of lattice matching and chemical effects in the design and preparation of templates for controlling conformational polymorphs.