Determination of Binding Constants and Gas Phase Stabilities of Artificial Carbohydrate Receptor Complexes Using Electrospray Mass Spectrometry

In recent years, binding studies to determine complex stabilities and selectivities of artificial carbohydrate receptors with glycosides have been mainly performed using H-1 NMR, isothermal titration calorimetry (ITC), and other spectroscopic titration techniques. Native electrospray ionization (ESI) mass spectrometry is used only to verify the complex stoichiometries, although determination of dissociation constants is also possible. Herein, the binding of a 1,3,5-substituted 2,4,6-triethylbenzene-based receptor (CHR) to four alkyl-beta-d-glucosides with varying alkyl side chain lengths (methyl (MGP), hexyl (HGP), octyl (OGP), and dodecyl (DGP)-beta-d-glucosides), which was analyzed by ESI Fourier transform ion cyclotron resonance mass spectrometry (ESI-FT-ICR-MS) under optimized spray conditions in both ion modes, is reported. The complexes of the receptor with different sugars could be detected in 1:1 and 2:1 stoichiometries. Dissociation constants calculated for the 1:1 complexes showed a stability trend depending on the length of the alkyl side chain of the sugar: CHR:DGP > CHR:OGP > CHR:HGP > CHR:MGP. Gas phase stabilities determined by CID-MS confirm this relative trend in binding affinities. These findings substantiate the validity and applicability of ESI-MS as a method for investigating noncovalent complex stabilities and thus support research in the field of molecular recognition of carbohydrates by artificial receptors.