Powder crystallography of pharmaceutical materials by combined crystal structure prediction and solid-state 1H NMR spectroscopy

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 4 (upper) Extracts from the aromatic region of the 13C–13C refocused INADEQUATE NMR spectrum and (lower) 1H–13C refocused INEPT NMR spectrum of flutamide.


A protocol for the ab initio crystal structure determination of powdered solids at natural isotopic abundance by combining solid-state NMR spectroscopy, crystal structure prediction, and DFT chemical shift calculations was evaluated to determine the crystal structures of four small drug molecules: cocaine, flutamide, flufenamic acid, and theophylline. For cocaine, flutamide and flufenamic acid, we find that the assigned ¹H isotropic chemical shifts provide sufficient discrimination to determine the correct structures from a set of predicted structures using the root-mean-square deviation (rmsd) between experimentally determined and calculated chemical shifts. In most cases unassigned shifts could not be used to determine the structures. This method requires no prior knowledge of the crystal structure, and was used to determine the correct crystal structure to within an atomic rmsd of less than 0.12 Å with respect to the known reference structure. For theophylline, the NMR spectra are too simple to allow for unambiguous structure selection.

 

 3 (upper) 1H (500 MHz) MAS NMR spectrum of flutamide: recorded in 8 scans with a recycle delay of 30 s at 60 kHz MAS and (lower) 13C (125 MHz) CPMAS NMR ...


 

 (upper) 1H (500 MHz) MAS NMR spectrum of flufenamic acid and (

 Molecular structure of cocaine (I), flutamide (II), flufenamic acid (


 

 Comparison between the structure of flutamide determined by powder 1H NMR and computational modelling here and

Powder crystallography of pharmaceutical materials by combined crystal structure prediction and solid-state ¹H NMR spectroscopy

Maria Baias,^a   Cory M. Widdifield,^a   Jean-Nicolas Dumez,^a   Hugh P. G. Thompson,^b   Timothy G. Cooper,^b   Elodie Salager,^a   Sirena Bassil,^a   Robin S. Stein,^a   Anne Lesage,^a   Graeme M. Day*^c and   Lyndon Emsley*^a  

*

Corresponding authors

^a

Université de Lyon, (CNRS/ENS-Lyon/UCB Lyon 1), Centre de RMN à Très Hauts Champs, 5 rue de la Doua, 69100 Villeurbanne, France
E-mail: lyndon.emsley@ens-lyon.fr
Fax: +33 4 78 89 67 61

^b

Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK

^c

Chemistry, University of Southampton, Highfield, Southampton, UK
E-mail: G.M.Day@soton.ac.uk

Phys. Chem. Chem. Phys., 2013,15, 8069-8080

DOI: 10.1039/C3CP41095A                                                                                                                                                                                                                                                                                   http://pubs.rsc.org/en/content/articlelanding/2013/cp/c3cp41095a#!divAbstract                                                 ////////////////////                                                                                                                                                                                                                                                                                                                                              odense,  denmark                                                                                                                                                                                                                                                                                                   

Nørregade 16, 5. tv, 5000 Odense C

Odense

City in Denmark

Odense is the third largest city in Denmark. It has a population of 173,814 as of January 2015, and is the main city of the island of Funen. Wikipedia

 


 
 

 
 

 


 

 

 

 


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