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

Jiawei Lin,Ying Wang,Yiming Ma,Lingyu Wang,Fei Liu,Peng Shi,Songgu Wu,Junbo Gong

doi:10.1107/s2052252521007119

Jiawei Lin, Ying Wang + Show 6 more

Open Access

https://doi.org/10.1107/s2052252521007119

Copy DOI

Abstract

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, wheren= 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.

Highlights

Polymorphism refers to the same compound with different crystal structures, classified as conformational and packing polymorphism
We developed a method to regulate the conformational polymorphs based on the structure similarity of a series of diacids
The epitaxially attached face was predicted by combining the chemical interactions and lattice matching to guide the template design

Summary

Introduction

Polymorphism refers to the same compound with different crystal structures, classified as conformational and packing polymorphism. Template-inducing heterogenous nucleation is a reliable method in screening and controlling polymorphism (Parambil et al, 2019; Thakore et al, 2020; Lopez-Mejıas et al, 2013; Tan et al, 2015). Various types of substrates including polymers (Lopez-Mejıas et al, 2009, 2011; Lang et al, 2002), SAMs (self-assembled monolayers) (Cox et al, 2007, Hiremath et al, 2004; Zhang et al, 2011), gels (Diao et al, 2012; Foster et al, 2017; Rahim et al, 2018) and organic crystals (Wijethunga et al, 2019; Arlin et al, 2011; Srirambhatla et al, 2016) were used to screen and control polymorphism. Compared with the amorphous substrates, the functional groups of organic crystal substrates possess specific orientation, the solute molecules can be compelled to align in a certain order through favourable interactions with the specific face (Zhang et al, 2019)

Objectives

Results

Conclusion