The conjugates of beta cylodextrins with R- or with S-Etodolac were characterized by NMR spectroscopy; and S-Etodolac alone was characterized by X-ray diffraction analysis. In solution, the R-Etodolac conjugate is soluble in water, the other epimer shows a very low solubility. The NMR characterization of the R-Etodolac conjugate in D(2)O shows that, in aqueous solution, the Edotolac moiety is self-included in the cavity, while the NMR characterization in MeOH of both conjugates underlines that, in this solvent, the Etodolac moiety is not included in the CD cavity. The X-ray structure determination of the S-Etodolac conjugate reveals a "sleeping swan"-like shape, with the covalently bonded Etodolac moiety being folded with the 8-ethyl group inserted inside the hydrophobic cavity of the beta-CD ring. The terminal methyl group of the 8-ethyl group enters the centre of cavity from the side of the primary hydroxyl groups and is buried inside the beta-CD macrocycle. The terminal methyl groups is positioned at a distance of 1.06 angstrom from the O(4) plane in the side of the primary hydroxyl groups. In addition to van der Waals interactions between the hydrophobic ethyl group and the beta-CD cavity, the folded conformation is further stabilized by one intramolecular H-bond involving the indole N-H group and the primary hydroxyl group of the glucose unit 7. Along the b axis, the beta-CD molecules are arranged in columns; the macrocycles form a herringbone pattern, so that the cavity of each beta-CD molecule is closed at each end by neighboring molecules. Within the layers, the beta-CD macrocycles are held together by a complicated intermolecular hydrogen bond network, in which numerous water molecules and hydroxyl groups are involved. (C) 2009 Wiley Periodicals, Inc. Biopolymers 91: 1227-1235, 2009.

Crystal and Molecular Structure of beta-Cyclodextrins Functionalized with the Anti-Inflammatory Drug Etodolac

Rizzarelli E;VECCHIO, Graziella;
2009

Abstract

The conjugates of beta cylodextrins with R- or with S-Etodolac were characterized by NMR spectroscopy; and S-Etodolac alone was characterized by X-ray diffraction analysis. In solution, the R-Etodolac conjugate is soluble in water, the other epimer shows a very low solubility. The NMR characterization of the R-Etodolac conjugate in D(2)O shows that, in aqueous solution, the Edotolac moiety is self-included in the cavity, while the NMR characterization in MeOH of both conjugates underlines that, in this solvent, the Etodolac moiety is not included in the CD cavity. The X-ray structure determination of the S-Etodolac conjugate reveals a "sleeping swan"-like shape, with the covalently bonded Etodolac moiety being folded with the 8-ethyl group inserted inside the hydrophobic cavity of the beta-CD ring. The terminal methyl group of the 8-ethyl group enters the centre of cavity from the side of the primary hydroxyl groups and is buried inside the beta-CD macrocycle. The terminal methyl groups is positioned at a distance of 1.06 angstrom from the O(4) plane in the side of the primary hydroxyl groups. In addition to van der Waals interactions between the hydrophobic ethyl group and the beta-CD cavity, the folded conformation is further stabilized by one intramolecular H-bond involving the indole N-H group and the primary hydroxyl group of the glucose unit 7. Along the b axis, the beta-CD molecules are arranged in columns; the macrocycles form a herringbone pattern, so that the cavity of each beta-CD molecule is closed at each end by neighboring molecules. Within the layers, the beta-CD macrocycles are held together by a complicated intermolecular hydrogen bond network, in which numerous water molecules and hydroxyl groups are involved. (C) 2009 Wiley Periodicals, Inc. Biopolymers 91: 1227-1235, 2009.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/20074
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 4
  • ???jsp.display-item.citation.isi??? 5
social impact