Mass spectrometry and molecular modeling studies on the inclusion complexes between alendronate and β-cyclodextrin

Complexation of alendronate sodium (AlnNa) with b-cyclodextrin (beta-CD) was studied by means of ESI-mass spectrometry. The experimental results show that stable 1:1 inclusion complexes between selected bisphosphonates and beta-CD were formed. In addition, complexes with different stoichiometry were observed. DFT/B3LYP calculations were performed to elucidate the different inclusion behavior between alendronate and beta-CD. Molecular modeling showed that the inclusion complex of Aln-beta-CD where the two phosphonate groups bound to the central carbon atom of bisphosphonate were inserted into the cavity of beta-CD from its "top'' side was thermodynamically more favorable than when they were inserted from its "bottom'' side; the complexation energy was -74.05 versus -60.85 kcal/mol. The calculations indicated that the formation of conventional hydrogen bonds was the main factor for non-covalent beta-CD:Aln complex formation and stabilization in the gas phase.