How Does Solvation Affect the Binding of Hydrophilic Amino Saccharides to Cucurbit[7]uril with Exceptional Anomeric Selectivity?

Abstract

Cucurbit[7]uril (CB[7]) is known to bind strongly to hydrophilic amino saccharide guests with exceptional α-anomer selectivities under aqueous conditions. Single-crystal X-ray crystallography and computational methods were used to elucidate the reason behind this interesting phenomenon. The crystal structures of protonated galactosamine (GalN) and glucosamine (GluN) complexes confirm the inclusion of α anomers inside CB[7] and disclose the details of the host-guest binding. Whereas computed gas-phase structures agree with these crystal structures, gas-phase binding free energies show preferences for the β-anomer complexes over their α counterparts, in striking contrast to the experimental results under aqueous conditions. However, when the solvation effect is considered, the binding structures drastically change and the preference for the α anomers is recovered. The α anomers also tend to bind more tightly and leave less space in the CB[7] cavity toward inclusion of only one water molecule, whereas loosely bound β anomers leave more space toward accommodating two water molecules, with markedly different hydrogen-bonding natures. Surprisingly, entropy seems to contribute significantly to both anomeric discrimination and binding. This suggests that of all the driving factors for the strong complexation of the hydrophilic amino saccharide guests, water mediation plays a crucial role in the anomer discrimination.

Unprotected Galactosamine as a Dynamic Key for a Cyclochiral Lock

“…This very specific ability of CB[7] has been further investigated for analytical purposes by ESI-mass spectrometry, whose speed and sensitivity are its most remarkable advantages. Interestingly, the α-preference, highlighted in solution by NMR spectrocopy and confirmed in the solid state by single X-ray crystallography, is reversed when the relevant stability of the host–guest complexes is calculated in the gas phase . This study, providing the actual arrangement of the guest in the receptor cavity, points to the central role of water mediation in anomer discrimination.…”

“…Interestingly, the α-preference, highlighted in solution by NMR spectrocopy and confirmed in the solid state by single X-ray crystallography, is reversed when the relevant stability of the host−guest complexes is calculated in the gas phase. 25 This study, providing the actual arrangement of the guest in the receptor cavity, points to the central role of water mediation in anomer discrimination. In particular, by only allowing the inclusion of several water molecules the binding free energy of the α-CB [7] complex is lowered enough to invert the stability ranking in the gas phase.…”

Localised Astrocyte Ca2+ Activity Regulates Neurovascular Coupling Responses to Active Sensing

“…These transi ons reflect changes in the general behavioral states, such as from sleep to awake or from a quiet wake state to a state of increased general whisking ac vity. Running is strongly associated with whisking (Sofroniew, Cohen et al 2014, Collins, Francis et al 2023) and evokes both a strong NVC response and astrocy c calcium responses (Ding, O'Donnell et al 2013, Wang, Jang et al 2016. Sensory evoked responses have classically been understood in the context of enhanced local synap c ac vity (Devor, Ulbert et al 2005).…”

Cucurbit[7]uril‐mediated Histidine Dimerization: Exploring the Structure and Binding Mechanism

“…Cucurbit[7]uril (CB7) is a versatile host for many organic compounds, with a high binding affinity to amines and aromatic molecules [1–6] . The molecule with the smallest dissociation constant (K D ) with CB7 is diamantane diamine, with K D =1.4×10 −18 ; the molecule with the second‐best K D is ferrocene diamine (3×10 −16 ) [7] .…”

“…Cucurbit [7]uril (CB7) is a versatile host for many organic compounds, with a high binding affinity to amines and aromatic molecules. [1][2][3][4][5][6] The molecule with the smallest dissociation constant (K D ) with CB7 is diamantane diamine, with K D = 1.4×10 À 18 ; the molecule with the second-best K D is ferrocene diamine (3×10 À 16 ). [7] CB7, in contrast to the smaller cucurbit [6]uril (CB6) and bigger cucurbit [8]uril (CB8), is highly soluble in water (20-30 mM), making it a promising molecule in supramolecular chemistry, especially considering that it is a non-toxic host that can be used in ex vivo and in vivo applications.…”