Inversion of Population Distribution of Felodipine Conformations at Increased Concentration in Dimethyl Sulfoxide Is a Prerequisite to Crystal Nucleation

Knowledge of the preferred conformations of biologically active compounds is of the utmost importance for a better understanding of the structure–activity relationships underlying their biological activity, as well as their mechanism of action. Moreover, investigating the mechanism of nucleation fro...

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 2014-02, Vol.103 (2), p.392-394
Main Authors: Khodov, Ilya A., Efimov, Sergey V., Nikiforov, Michael YU, Klochkov, Vladimir V., Georgi, Nikolaj
Format: Article
Language:English
Subjects:
Algorithms
Calcium Channel Blockers - chemistry
Crystallization
Dimethyl Sulfoxide - chemistry
Felodipine - chemistry
Magnetic Resonance Imaging
Magnetic Resonance Spectroscopy
Models, Molecular
Molecular Conformation
NMR spectroscopy
nucleation
polymorphism
structure
X-Ray Diffraction
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Summary:Knowledge of the preferred conformations of biologically active compounds is of the utmost importance for a better understanding of the structure–activity relationships underlying their biological activity, as well as their mechanism of action. Moreover, investigating the mechanism of nucleation from a saturated solution can facilitate the discovery and preparation of new polymorphic forms. To search regularities in the crystal nucleation of biologically active compounds (drugs) from a saturated solution, we studied the conformational preference of felodipine in dilute and saturated solution in dimethyl sulfoxide. The inversion of conformation distribution at increased concentration occurs: conformers that dominate in a dilute solution become the least abundant in the saturated one. Conformers that dominate in the saturated solution are of the same type as revealed in crystalline state by X-ray.
ISSN:0022-3549
1520-6017
DOI:10.1002/jps.23833