A study of supramolecular host–guest interaction of dothiepin and doxepin drugs with cyclodextrin macrocycles

• Published in: Journal of molecular structure 2014-06, Vol.1067, p.252-260
• Main Authors: Rajendiran, N., Sankaranarayanan, R.K., Saravanan, J.
• Format: Article
• Language: English
• Subjects: Chains; Cyclodextrin; Cyclodextrins; Dothiepin; Doxepin; Drugs; Entropy; Fluorescence; Inclusion complex; Inclusions; Macrocyclic compounds; Nanostructure; Scanning electron microscopy; Supramolecular
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2014.03.051

[Display omitted] •Spectral studies reveal that DOT and DOX drugs form different inclusion complexes with α- and β-CD.•Both drugs exhibit short life time in aqueous medium and higher in CD medium.•DOT self assembled to form nano-sized spheres and particles with CD.•Nanostructures are formed through the intermolecular hydrogen bonding.•The alkyl chain encapsulation is more favoured in the α-CD cavity than aromatic ring of drugs. Inclusion complexation behavior of dothiepin (DOT) and doxepin (DOX) with two cyclodextrins (α-CD and β-CD) were studied by absorption, fluorescence, time resolved fluorescence, scanning electron microscope (SEM), transmission electron microscope (TEM), Fourier transformation infrared spectroscopy (FT-IR), differential scanning colorimetry (DSC), powder X-ray diffraction (PXRD), proton nuclear magnetic resonance (1H NMR) and molecular modeling methods. Absorption and fluorescence spectral studies reveal that both drugs form different types of inclusion complexes with α-CD and β-CD. DOT and DOX exhibit short life time in aqueous medium (DOT∼2.29ns, DOX∼1.89ns) and higher in CD medium (DOT:α-CD∼3.45ns, DOT:β-CD∼4.84ns, DOX:α-CD∼3.55ns and DOT:β-CD∼4.33ns). The supramolecular structure of the nano-sized sphere and agglomerate was established by TEM. Alkyl chain and aromatic ring protons of the drug molecule are entrapped in the CD nanocavities. The significant proton chemical shifts give evidence for expected inclusion complex formation. PM3 calculations suggest that the alkyl chain encapsulation is most energetically favored in α-CD. The positive free energy and entropy changes indicated that both inclusion complexation processes are non-spontaneous and entropy driven.