Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 418, Issue 2, Pages 179-186Publisher
ELSEVIER
DOI: 10.1016/j.ijpharm.2011.04.062
Keywords
Polymorphism; Molecular conformation; Intermolecular interactions; Conceptual density functional calculations
Categories
Funding
- NSF [DMR-0449633, DMR-1006364]
- Division Of Materials Research
- Direct For Mathematical & Physical Scien [1321941] Funding Source: National Science Foundation
Ask authors/readers for more resources
Tolfenamic acid exhibits conformational polymorphism. The molecules in its two commonly occurred crystal structures form similar hydrogen-bonded dimers but differ in conformation. The conformational variance was analyzed by electronic calculation methods with the aim to unravel intrinsic connection between the conformational flexibility and intermolecular interactions in the polymorphs. The study was conducted mainly by conceptual density functional theory (OFT) and natural bond orbital (NBO) analysis. It is found that the conformational polymorphism is resulted from the energy competition between intramolecular pi-conjugation and intermolecular hydrogen bonding. By adapting conformation that departs from being the most energetically stable, tolfenamic acid molecules can strengthen the intermolecular hydrogen-bonding interactions in the crystals. The study illustrates how the molecule's electronic properties are influenced by conformational variation and, inherently, how the intermolecular interactions become regulated. Moreover, understanding molecular interaction and crystal packing necessitates electronic structure calculation and analysis, which can be further facilitated by utilizing DFT and NBO concepts. (C) 2011 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available