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Abstract
Racemic ketoprofen (KP) and β-cyclodextrin (β-CD) powder samples from co-precipitation (1), evaporation (2), and heating-under-reflux (3) were analysed using X-ray techniques and nuclear magnetic resonance (NMR) spectroscopy. On the basis of NMR studies carried out in an aqueous solution, it was found that in the samples obtained by methods 1 and 2, there were large excesses of β-CD in relation to KP, 10 and 75 times, respectively, while the sample obtained by method 3 contained equimolar amounts of β-CD and KP. NMR results indicated that KP/β-CD inclusion complexes were formed and the estimated binding constants were approximately 2400 M−1, showing that KP is quite strongly associated with β-CD. On the other hand, the X-ray single-crystal technique in the solid state revealed that the (S)-KP/β-CD inclusion complex with a stoichiometry of 2:2 was obtained as a result of heating-under-reflux, for which the crystal and molecular structure were examined. Among the methods used for the preparation of the KP/β-CD complex, only method 3 is suitable.
Keywords: KP/β-CD inclusion complex, NMR, XRPD, crystal and molecular structure
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Three approaches to the problem of solvent water in strucutre were described in Supplementary Materials (pages 1-2 of 1-16):
Betlejewska-Kielak Katarzyna, Bednarek Elżbieta, Budzianowski Armand, Michalska Katarzyna, Maurin Jan K.
Comprehensive Characterisation of the Ketoprofen-β-Cyclodextrin Inclusion Complex Using X-Ray Techniques and NMR Spectroscopy
Molecules 26(13), (2021) 4089.
DOI: 10.3390/molecules26134089.
a) use a larger number of isotropic oxygen atoms with partial occupation for water molecules.
b) use a smaller number of oxygen atoms with anisotropic displacement parameters.
c) use a PLATON SQUEEZE procedure to omit disordered molecules of solvent with volume up 30%.
The second technique is descrived in Supplementary Materials according to „SHELXL-93 A Program for the Refinement of Crystal Structures” and „User guide to crystal structure refinement with SHELXL”, both by George Sheldrick.
FMAP 2
PLAN 200 2.3
CGLS 10
CONN 0 O01W > LAST