Cucurbit[7]uril recognition of glucosamine anomers in water

We investigate host–guest complexation between cucurbit[7]uril and the α- and β-anomers of glucosamine, in its neutral (GN), protonated (GP), and acetylated (GA) forms. Molecular dynamics simulations (MD) were used to study the structures of the resulting inclusion complexes and their dynamics. The binding affinities of the complexes were determined experimentally by using indicator displacement assay and further evaluated by MM-PBSA analysis. Electrostatic and van der Waals interactions contribute favourably to complex stability, with the former making the largest contribution in the case of protonated-glucosamine. MM-PBSA analysis shows that the CB7 preferentially binds the β-anomers of GP and GA and the α-anomer of GN. Thermodynamic integration (TI) was used to calculate the relative stabilities of both anomers in the bound state and to compute the p K a shift of the glucosamine upon complexation. TI Results indicate that the CB7 binds the α-anomers of GN and GA with higher affinity, while the reverse was true for the β-anomer of GP. The preferred binding of GP over GN resulted in complexation induced p K a shift.