Molecular arrangements in crystals of racemic and enantiopure forms of N-carbamoyl-2-phenylbutyramide and 2-phenylbutyramide: differences and similarities
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Arcadius V. Krivoshein
,
Sergey V. Lindeman
Abstract
As solid drugs may be regarded as “pharmaceutical materials”, molecular pharmaceutics of such drugs is expected to benefit from application of materials science concepts. In this paper, we used a structural chemistry approach to explain the dramatic difference in solubility between two structurally related antiepileptic drugs, N-carbamoyl-2-phenylbutyramide (NC2PBA) and 2-phenylbutyramide (2PBA). Since both of these compounds are chiral, we chromatographically separated the enantiomers and examined them along with the racemic forms. A combination of experimental (single-crystal X-ray diffraction, IR spectroscopy) and computational (crystal lattice energy calculations, Hirshfeld surface analysis) techniques was employed to determine the structural differences between these two compounds in the crystalline state. We found that while NC2PBA and 2PBA have similar molecular packing arrangements, the former compound is distinguished by a more extensive network of hydrogen bonds. Thus, the higher density, higher melting point, and lower solubility of crystalline NC2PBA compared to crystalline 2PBA may be largely explained by the differences in hydrogen bonding. We also found that for each of these compounds there are no major differences in molecular packing (and, correspondingly, in crystal lattice energies) between racemic and enantiopure forms.
Acknowledgements
We thank Drs. Marina S. Fonari (Institute of Applied Physics, Chişinău, Moldova) and Victor N. Khrustalev (Peoples’ Friendship University, Moscow, Russia) for fruitful discussions of the crystallographic data reported in this paper. A. V. K. gratefully acknowledges the funding from the Welch Foundation Departmental Grant (award No. BC-0022; the PI of this grant is Dr. Daniel Z. Wang) and the University of Houston – Clear Lake Faculty Research Support Fund (to A. V. K.; award No. FRSF#1176). T. V. T., V. S., and B. B. A. were supported by a Partnership for Research and Education in Materials (PREM) grant from the National Science Foundation (to T. V. T., award No. 1523611). The Agilent UHPLC system used for the analytical separation of NC2PBA enantiomers was acquired using a Major Research Instrumentation grant from the National Science Foundation (award No. 0958901; the PI of that grant was Dr. Daniel Z. Wang).
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Supplementary Material
The online version of this article offers supplementary material (https://doi.org/10.1515/zkri-2018-2051).
Article note:
Some of the results described in this article were presented in preliminary form as an invited talk (Timofeeva, T. V., Krivoshein, A. V., Sandhu, B. K., Huang, J., and Chen, Y., “Structural and pharmacological studies of anticonvulsant carboxamides and acetylureas”) at the American Crystallographic Association Annual Meeting, Albuquerque, New Mexico, May 24–28, 2014.
©2018 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Graphical Synopsis
- A new disodium hafnium borate Na2Hf(BO3)2: synthesis, crystal structure, DFT calculations and luminescent properties
- Crystal structures and Hirshfeld surface analyses of seven 7-aryl-4,7-dioxoheptanoic acids: differing carboxylic acid interactions leading to dimers, chains and three-dimensional arrays
- Molecular arrangements in crystals of racemic and enantiopure forms of N-carbamoyl-2-phenylbutyramide and 2-phenylbutyramide: differences and similarities
- Red photo- and electroluminescent half-lantern cyclometalated dinuclear platinum(II) complex
- Tyrosinase inhibition potency of phthalimide derivatives: crystal structure, Hirshfeld surface analysis and molecular docking studies
Artikel in diesem Heft
- Frontmatter
- Graphical Synopsis
- A new disodium hafnium borate Na2Hf(BO3)2: synthesis, crystal structure, DFT calculations and luminescent properties
- Crystal structures and Hirshfeld surface analyses of seven 7-aryl-4,7-dioxoheptanoic acids: differing carboxylic acid interactions leading to dimers, chains and three-dimensional arrays
- Molecular arrangements in crystals of racemic and enantiopure forms of N-carbamoyl-2-phenylbutyramide and 2-phenylbutyramide: differences and similarities
- Red photo- and electroluminescent half-lantern cyclometalated dinuclear platinum(II) complex
- Tyrosinase inhibition potency of phthalimide derivatives: crystal structure, Hirshfeld surface analysis and molecular docking studies
