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Supramolecular synthon pattern in solid clioquinol and cloxiquine (APIs of antibacterial, antifungal, antiaging and antituberculosis drugs) studied by ³⁵Cl NQR, ¹H-¹⁷O and ¹H-¹⁴N NQDR and DFT/QTAIM.

Faculty of Physics, Adam Mickiewicz University, Umultowska 85, 61-614 Poznań, Poland.
Journal of Molecular Modeling (Impact Factor: 1.87). 11/2010; 17(7):1781-800. DOI: 10.1007/s00894-010-0876-4
Source: PubMed

ABSTRACT The quinolinol derivatives clioquinol (5-chloro-7-iodo-8-quinolinol, Quinoform) and cloxiquine (5-chloro-8-quinolinol) were studied experimentally in the solid state via ³⁵Cl NQR, ¹H-¹⁷O and ¹H-¹⁴N NQDR spectroscopies, and theoretically by density functional theory (DFT). The supramolecular synthon pattern of O-H···N hydrogen bonds linking dimers and π-π stacking interactions were described within the QTAIM (quantum theory of atoms in molecules) /DFT (density functional theory) formalism. Both proton donor and acceptor sites in O-H···N bonds were characterized using ¹H-¹⁷O and ¹H-¹⁴N NQDR spectroscopies and QTAIM. The possibility of the existence of O-H···H-O dihydrogen bonds was excluded. The weak intermolecular interactions in the crystals of clioquinol and cloxiquine were detected and examined. The results obtained in this work suggest that considerable differences in the NQR parameters for the planar and twisted supramolecular synthons permit differentiation between specific polymorphic forms, and indicate that the more planar supramolecular synthons are accompanied by a greater number of weaker hydrogen bonds linking them and stronger π···π stacking interactions.

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