Spectroscopic (fluorescence, 1D-ROESY) and theoretical studies of the thiabendazole and β-cyclodextrin inclusion complex

The inclusion complex between the anti-helminthic drug thiabendazole (TBZ) and the beta-cyclodextrin (beta CD) was characterized in solution using fluorescence and H-1-Nuclear Magnetic Resonance spectroscopy and studied theoretically by semi empirical PM3 and density functional theory (DFT) quantum mechanical calculations. Thermodynamic stability associated with the formation of the TBZ:beta CD inclusion complex in aqueous solution was determined treating the drug's fluorescence enhancement in the presence of cyclodextrin by a non-linear model, which indicated a moderate host-guest affinity at equilibrium (K 150 +/- A 31 at 25 A degrees C). Its supramolecular structure in solution was studied through the 1D-ROESY NMR experiment, which produced evidence that the guest molecular encapsulation occurs preferably via the drug's benzimidazole group. Theoretical study employing molecular optimization with the semi empirical PM3 method provided two energetic-equivalent complex structures that are in accordance with the NMR experimental evidences. Single point energy calculations with DFT at the B3LYP/6-31G (d,p) level suggest the most stable structure of the inclusion complex and further comprehension on the interactions and conformational strains involved in its formation.