The modes of complexation of benzimidazole with aqueous β-cyclodextrin explored by phase solubility, potentiometric titration, 1H-NMR and molecular modeling studies

The results of rigorous modeling of phase solubility diagrams, pH solubility profiles and potentiometric titrations revealed the following for benzimidazole (BZ) and BZ/beta-CD complexation in aqueous solution: (a) the pK (a) value of BZ estimated at 5.66 +/- 0.08 was reduced to 5.33 +/- 0.06 in the presence of 15 mM beta-CD at 25 A degrees C, thus indicating inclusion complex formation; (b) BZ forms soluble 1:1 and 2:1 BZ/beta-CD complexes with complex formation constants K-11 = 104 +/- 8 M-1 and K-21 = 16 +/- 6 M-1; (c) protonated BZ forms only 1:1 complex with K-11 = 42 +/- 12 M-1; (d) H-1-NMR studies in D2O showed significant upfield chemical shift displacements for inner cavity beta-CD protons indicating inclusion complex formation, while (e) Molecular modeling of BZ-beta-CD interactions in water clearly indicated complete inclusion of one BZ molecule into the beta-CD cavity.