Preparation, characterization and molecular modeling studies of the inclusion complex of Caffeine with Beta-cyclodextrin

• Caffeine (CA) molecule forms stable inclusion complex with β-CD and it is analyzed in liquid and solid state.
• The BH plot is obtained on the basis of absorbance and fluorescence intensity of CA by the addition of β-CD and confirms the stoichiometric ratio is found to be 1:1.
• The lifetime analysis supports the formation of complex in liquid state.
• FT-IR, SEM, TG/DSC and powder XRD are used to characterize the complex formation in solid state.
• The orientation and proposed structure of the complex is presented according to molecular docking study.

The formation through supramolecular interaction of a host–guest inclusion complex of caffeine (CA) with nano-hydrophobic cavity beta-cyclodextrin (β-CD) is achieved by a physical mixture, a kneading method and a co-precipitation method. The formation of the inclusion complex of CA with β-CD in solution state is confirmed by UV–visible spectrophotometer, fluorescence spectrophotometer and time-resolved fluorescence spectrophotometer. The stoichiometry of the inclusion complex is 1:1; the imidazole ring and pyrimidine ring of caffeine is deeply entrapped in the beta-cyclodextrin as confirmed by spectral shifts. The Benesi–Hildebrand plot is used to calculate the binding constant of the inclusion complex of CA with β-CD at room temperature. The Gibbs free energy change of the inclusion complex process is calculated and the process is found to be spontaneous. The thermal stability of the inclusion complex of CA with β-CD is analyzed using differential scanning calorimetry. The crystal structure modification of a solid inclusion complex is confirmed by scanning electron microscopy image analysis. The formation of the inclusion complex of CA with β-CD in the solid phase is also confirmed by FT-IR and XRD. The formation of the inclusion complex between CA and β-CD, as confirmed by molecular docking studies, is in good relationship with the results obtained through different experimental methods.

1:1 stoichiometric inclusion complex CA with β-CDx proposed by Patchdock server.Figure optionsDownload as PowerPoint slide