Supramolecular Interaction of Primaquine with Native β-Cyclodextrin

Abstract

The supramolecular host–guest inclusion complex of Primaquine (PQ) with the nano-hydrophobic cavity of beta-cyclodextrin (β-CD) was prepared by physical mixing, kneading and co-precipitation methods. The formation of an inclusion complex in PQ with β-CD in the solution phase has been confirmed by UV–visible and fluorescence spectroscopy. The stoichiometry of the inclusion complex is 1:1; the Primaquine molecule is deeply entrapped in the cavity of β-cyclodextrin, which was confirmed by analysis of spectral shifts and corresponding absorbance and fluorescence intensities. The Benesi–Hildebrand plot was used to calculate the binding constant of the inclusion complex of PQ with β-CD at room temperature. The Gibbs energy change of the inclusion complex process has been calculated. The $$ {\text{p}}K_{\text{a}} $$ and $$ {\text{p}}K_{\text{a}}^{*} $$ for the monocation and neutral equilibrium of PQ in aqueous and β-CD media are discussed. The thermal stability for the inclusion complex of PQ with β-CD has been analyzed using differential scanning calorimetry. The modification of the crystal structure to amorphous for the solid inclusion complex was confirmed by powder X-ray diffraction. The structure of the complex is proposed by docking studies using the Patch-Dock server. A cytotoxic analysis was also carried out for the pure PQ and its solid complex on the MDA MB 231 cell line and showed that the activity is good for both substances. The cytotoxicity neither improved nor decreased with the formation of the inclusion complex with β-CD.