title: Inversion of population distribution of felodipine conformations at increased concentration in dimethyl sulfoxide is a prerequisite to crystal nucleation.
abstract: 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.
authors.affiliation: G. A. Krestov Institute of Solution Chemistry, Russian Academy of Sciences, Ivanovo, 153045, Russia.
authors.forename: Ilya A
authors.initials: IA
authors.lastname: Khodov
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Efimov
authors.forename: Michael Yu
authors.initials: MY
authors.lastname: Nikiforov
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Klochkov
authors.forename: Nikolaj
authors.initials: N
authors.lastname: Georgi
mesh_terms: D000465:Algorithms; D002121:Calcium Channel Blockers / Q000737:chemistry*; D003460:Crystallization; D004121:Dimethyl Sulfoxide / Q000737:chemistry*; D015736:Felodipine / Q000737:chemistry*; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D014961:X-Ray Diffraction
chemical_list: D002121:Calcium Channel Blockers; D015736:Felodipine; D004121:Dimethyl Sulfoxide
keywords: NMR spectroscopy; crystallization; nucleation; polymorphism; structure