Structural characterization of cyclodextrin and maltodextrin alkali-metal coordination <i>via</i> ion mobility-mass spectrometry and computational modeling

Cyclodextrins (CDs) are macrocyclic oligosaccharides that have the ability to form host-guest inclusion complexes due to their amphiphilic properties, thereby allowing for an increase in the solubility and bioavailability of encapsulated small molecules, such as food constituents and active pharmaceutical ingredients (APIs). While solution-phase properties of CD inclusion complexes have been extensively studied, less is known about the prevailing coordination environment of metal-CD complexes in the absence of bulk solvent. Here, we investigate the gas-phase structural implications of alkali-metal complexation with the three naturally occurring cyclodextrins (αCD, βCD, and γCD) and a suite of linear maltodextrins using structurally-selective ion mobility-mass spectrometry (IM-MS) analysis. For the maltodextrins, the IM-MS analysis revealed an expected linear relationship between the number of monosaccharide units and the measured collision cross section (CCS), however, the CDs exhibited complex size-mass behavior, notably with βCD adopting nearly the same CCS values as the larger γCD, irrespective of the charge carrier. CCS measurements in helium drift gas were obtained on a drift tube IM instrument and used to align to computational modeling outputs which were interpreted for atomistic-level information including bond distances and coordination geometries. Predicted structures for [CD + Na]⁺ indicate the unusual gas-phase structural behavior of CDs is a consequence of different charge location preferences for αCD and γCD <i>versus</i> βCD. Taken together, this work provides a structural context for the underlying metal-host interactions that serve as scaffolds for higher-order CD complexation and supramolecular assemblies.