Disorderly Conduct of Benzamide IV: Crystallographic and Computational Analysis of High Entropy Polymorphs of Small Molecules

Journal Article · Wed Mar 11 00:00:00 EDT 2020 · Crystal Growth and Design

DOI:https://doi.org/10.1021/acs.cgd.0c00096· OSTI ID:1631968

Fellah, Noalle  ^[1]; Shtukenberg, Alexander G.  ^[1]; Chan, Eric J.  ^[1]; Vogt-Maranto, Leslie  ^[1]; Xu, Wenqian ^[2]; Li, Chao ^[1]; Tuckerman, Mark E.  ^[3]; Kahr, Bart  ^[1]; Ward, Michael D.  ^[1]

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1. New York Univ. (NYU), NY (United States)
2. Argonne National Lab. (ANL), Argonne, IL (United States)
3. New York Univ. (NYU), NY (United States); East China Normal Univ. (ECNU), Shanghai (China)

Benzamide, a simple derivative of benzoic acid and a common intermediate of pharmaceutical compounds, was reported to form two polymorphs in 1832, but the single crystal structure of the more stable form was not solved until 1959. Nearly 50 years later, the second form was characterized by powder diffraction, followed shortly thereafter by characterization of a third form, a polytype of the most thermodynamically stable Form I. These two new forms, Forms II and III, are metastable. Herein, we describe a fourth polymorph, Form IV, discovered by melt crystallization concurrently with its crystallization under confinement at small length scales (<10 nm), where it is stable indefinitely. Form III exists under confinement in larger pores, and melting point data for different pore sizes corroborate the existence of Form IV below 10 nm. Form IV is highly disordered, precluding indexing of powder diffraction data other than hk0 reflections. Nonetheless, a combination of powder X-ray diffraction and computational crystal structure prediction reveals that Form IV contains a 2D motif resembling that of Form II, but with longrange order in the third dimension masked by ubiquitous stacking faults. This approach relies on distilling a large number of candidate structures to a few possible disorder models based on benzamide tetrads that organize in 2D parquet-like tiles, with organization along the third dimension, that can be modeled with various stacking fault configurations having distinct intermolecular interactions and translations in the dimension orthogonal to the tiling planes. These observations reveal a bewildering crystallographic complexity for such a simple molecule. Nonetheless, the approach described herein demonstrates that challenging structures that may be abandoned prematurely because of poor crystallinity, twinning, or disorder can be solved.

• Research Organization: Argonne National Lab. (ANL), Argonne, IL (United States)
• Sponsoring Organization: National Science Foundation (NSF) - Directorate for Mathematical and Physical Sciences Division of Materials Research (MPS-DMR); National Science Foundation (NSF) - Directorate for Mathematical and Physical Sciences Division of Chemistry (MPS/CHE); New York University; USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities Division
• Grant/Contract Number: AC02-06CH11357
• OSTI ID: 1631968
• Journal Information: Crystal Growth and Design, Vol. 20, Issue 4; ISSN 1528-7483
• Publisher: American Chemical Society
• Country of Publication: United States
• Language: English

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY