title: Mass spectrometry and molecular modeling studies on the inclusion complexes between alendronate and β-cyclodextrin.
abstract: Complexation of alendronate sodium (AlnNa) with β-cyclodextrin (β-CD) was studied by means of ESI-mass spectrometry. The experimental results show that stable 1:1 inclusion complexes between selected bisphosphonates and β-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 β-CD. Molecular modeling showed that the inclusion complex of Aln-β-CD where the two phosphonate groups bound to the central carbon atom of bisphosphonate were inserted into the cavity of β-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 β-CD:Aln complex formation and stabilization in the gas phase.
authors.affiliation: Department of Drug Chemistry, Medical University of Warsaw, 1 Banacha Street, 02-097 Warsaw, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Biernacka
authors.affiliation: National Medicines Institute, 30/34 Chełmska Street, 00-725 Warsaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Betlejewska-Kielak
authors.affiliation: National Medicines Institute, 30/34 Chełmska Street, 00-725 Warsaw, Poland.
authors.forename: Janina
authors.initials: J
authors.lastname: Witowska-Jarosz
authors.affiliation: Department of Drug Chemistry, Medical University of Warsaw, 1 Banacha Street, 02-097 Warsaw, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Kłosińska-Szmurło
authors.affiliation: Department of Drug Chemistry, Medical University of Warsaw, 1 Banacha Street, 02-097 Warsaw, Poland ; National Medicines Institute, 30/34 Chełmska Street, 00-725 Warsaw, Poland.
authors.forename: Aleksander P
authors.initials: AP
authors.lastname: Mazurek
keywords: Alendronate sodium; Electrospray ionization; Inclusion complex; Mass spectrometry; Molecular modeling; β-Cyclodextrin