Investigation of spectroscopic properties and molecular dynamics simulations of the interaction of mebendazole with β-cyclodextrin

The effect of β-cyclodextrin (β-CD) on the spectroscopic properties of mebendazole, MBZ, in aqueous solution was investigated at pH values of 2.0, 4.0, 6.0, 8.0, 10.0, and 12.0, where mebendazole exists as protonated (HMBZ+), neutral (MBZ), or deprotonated (MBZ−) forms. Mebendazole shows two absorption bands at 236 nm and 288 nm at pH 2.0, which are shifted gradually as pH increases to 265 nm and 350 nm at pH 12.0, and one fluorescence emission band at 463 nm at all pH values. In the presence of β-CD, the emission band at 463 nm was enhanced and new emission bands in the range 300–350 nm were observed at pH 2.0–6.0. In addition, pKa1 of MBZ increased and pKa2 decreased, indicating that both benzimidazole and carbamate moieties are involved in complex formation, which is confirmed by the results of molecular dynamics (MD) simulations. Benesi–Hildebrand analysis and MD simulations show that binding stoichiometry of neutral MBZ/β-CD complex is 1:2, where the wide rims of both CD macrocycles face each other, while a stoichiometry of 1:1 was observed for the protonated HMBZ+/β-CD complex. Experimentally obtained thermodynamic parameters show that complexation of MBZ with β-CD is a spontaneous enthalpy driven process (ΔG° = −36.3 kJ mol−1 for MBZ/β-CD and ΔG° = −25.9 kJ mol−1 for HMBZ+/β-CD), while binding free energy computed through MM-PBSA computational method shows that driving forces for complex formation is van der Waals interactions and H-bonding.