TY - JOUR
T1 - Disorderly Conduct of Benzamide IV
T2 - Crystallographic and Computational Analysis of High Entropy Polymorphs of Small Molecules
AU - Fellah, Noalle
AU - Shtukenberg, Alexander G.
AU - Chan, Eric J.
AU - Vogt-Maranto, Leslie
AU - Xu, Wenqian
AU - Li, Chao
AU - Tuckerman, Mark E.
AU - Kahr, Bart
AU - Ward, Michael D.
N1 - Funding Information:
This work was supported by the National Science Foundation under award numbers DMR-1708716 and DMR-1608374 and the New York University Materials Research Science and Engineering Center (MRSEC) program of the National Science Foundation under award number DMR-1420073. The authors acknowledge Dr. Chunhua Hu (NYU Department of Chemistry X-ray Diffraction Facility), the NSF Chemistry Research Instrumentation and Facilities Program (CHE-0840277), and NSF MRSEC Program under award number DMR-0820341 for the powder microdiffractometer with GADDS. This work was supported by computational resources provided by High Performance Computing at New York University. Use of the Advanced Photon Source at Argonne National Laboratory was supported by the U.S. Department of Energy, Office of Science, and Office of Basic Energy Sciences, under contract no. DE-AC02-06CH11357. We are grateful to Dr. Lynn W. Ribaud and Dr. Saul D. Lapidus for providing assistance in collecting synchrotron powder diffraction data at Advanced Photon Source. The authors thank Prof. Qiang Zhu for a preliminary crystal structure prediction search and Prof. Martin Schmidt for helpful discussions on benzamide structure.
Publisher Copyright:
Copyright © 2020 American Chemical Society.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - 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 long-range 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.
AB - 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 long-range 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.
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U2 - 10.1021/acs.cgd.0c00096
DO - 10.1021/acs.cgd.0c00096
M3 - Article
AN - SCOPUS:85081954441
VL - 20
SP - 2670
EP - 2682
JO - Crystal Growth and Design
JF - Crystal Growth and Design
SN - 1528-7483
IS - 4
ER -