Structural Elucidation of Specific Non-covalent Association of Folic Acid with Native Cyclodextrins using an IM-MS and Theoretical Approach.

TitleStructural Elucidation of Specific Non-covalent Association of Folic Acid with Native Cyclodextrins using an IM-MS and Theoretical Approach.
Publication TypeJournal Article
Year of Publication2014
AuthorsZimnicka, Magdalena, Troć Anna, Ceborska Magdalena, Jakubczak Michał, Koliński Michał, and Danikiewicz Witold
JournalAnal Chem
Date Published2014 Apr 8
ISSN1520-6882
Abstract<p>The combination of ion mobility mass spectrometry studies and theoretical calculations including docking studies permitted a detailed structural description of non-covalent complexes of folic acid (FA) and native cyclodextrins (α-CD, β-CD and γ-CD). The mode of non-covalent association depended on the cavity size of the cyclodextrin. The structure of FA/α-CD represented the exclusion complex in which the aminobenzoic moiety and the aromatic pteridine ring of folic acid remain outside the cyclodextrin cavity, while the glutamate residue is anchored in the interior of the α-cyclodextrin. A rotaxane-type structure was proposed for the FA/β-CD complex with the aminobenzoic part of FA being trapped in the central cavity of β-CD. The glutamate residue and the aromatic pteridine ring interact with the primary and secondary rim hydroxyl residues, respectively, enhancing complex stability. Two possible structures of FA/γ-CD were suggested, the first one being analogous to the FA/β-CD complex and the second one being more stable - in which the aromatic pteridine ring penetrates into the CD cavity while the glutamate residue with the aminobenzoic part of FA are exposed to the cone exterior of CD at its wider edge. Further insight into the association behavior of the folic acid towards cyclodextrins evaluated by thermodynamic calculations indicates that the process is highly exothermic. The complex stability increased in the order FA/α-CD < FA/β-CD < FA/γ-CD. This order is consistent with the previously determined relative gas-phase stability established based on the dissociation efficiency curves of the FA/CD complexes.</p>
DOI10.1021/ac4039042
Alternate JournalAnal. Chem.
PubMed ID24712714