Solid-state CP/MAS13C NMR studies on conformational polymorphism in sertraline hydrochloride, an antidepressant drug

Autor:	Robert Glaser, Artem Novoselsky
Rok vydání:	2002
Předmět:	Crystallography Solid-state nuclear magnetic resonance Chemistry Chemical shift Alkane stereochemistry Proton NMR General Materials Science Density functional theory General Chemistry Carbon-13 NMR Dihedral angle Spectral line
Zdroj:	Magnetic Resonance in Chemistry. 40:723-728
ISSN:	1097-458X 0749-1581
DOI:	10.1002/mrc.1093
Popis:	The C(2) isotropic chemical shift values in solid-state CP/MAS 13C NMR spectra of conformational polymorphs Form I (δ 28.5) and III (δ 22.9) of (1S,4S)-sertraline HCl (1) were correlated with a γ-gauche effect resulting from the respective 162.6° antiperiplanar and 68.8° (+)-synclinal C(2) C(1) N CH3 torsion angles as measured by X-ray crystallography. The similarity of the solution-state C(2) chemical shifts in CD2Cl2 (δ 22.8) and DMSO-d6 (δ 23.4) with that for Form III (and other polymorphs having C(2) C(1) N CH3 (+)-synclinal angles) strongly suggests that a conformational bias about the C(1) N bond exists for 1 in both solvents. This conclusion is supported by density functional theory B3LYP/6-31G(d)-calculated relative energies of C(1) N rotameric models: (kcal) 0.00 [73.8 °C(2) C(1) N CH3 torsion angle], 0.88 (168.7°), and 2.40 (−63.4°). A Boltzmann distribution of these conformations at 25 °C is estimated to be respectively (%) 80.3, 18.3, and 1.4. Copyright © 2002 John Wiley & Sons, Ltd.
Databáze:	OpenAIRE
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