Molecular Interactions and Inclusion Phenomena in Substituted β-Cyclodextrins. Simple Inclusion Probes: H2O, C, CH4, C6H6, NH4+, HCOO−

Using a simple molecular mechanics approach interaction energy profiles of simple probes (C, CH4, C6H6, H2O, NH4+, and HCOO-) passing through the center of the β-CD ring cavity along the main molecular symmetry axis were first evaluated. Molecular Electrostatic Potential (MEP) values along the same path were also evaluated. The effect of the flexibility of the host β-CD molecule together with solute-solvent (H2O) interactions have been represented by averaging structures of MD calculations for β-CD alone and β-CD surrounded by 133 H2O molecules. The effect of various substitutions of β-CD has also been evaluated. Small symmetric hydrophobic probes (such as C, CH4, C6H6) are predicted to form stable inclusion complexes with non-substituted and substituted β-CDs, the probe position typically being near the cavity center. The stability of the inclusion complexes will increase with increasing size and aliphatic character of the probe. Small polar and charged probes (such as H2O, NH4+, HCOO-) are predicted to prefer the interaction with the solvent (water) in the bulk phase rather than the formation of inclusion complexes with non-substituted and substituted β-CDs. Guest–host interactions in the stable inclusion complexes with hydrophobic probes are almost entirely dominated by dispersion interactions. The MEP reaches magnitudes close to zero in the center of the non-substituted β-CD ring cavity and in most of the studied substituted β-CDs and shows maximum positive or negative values outside of the cavity, near the ring faces. Substitution of β-CD by neutral substituents leads to enhanced binding of hydrophobic probes and significant changes in the MEP profile along the β-CD symmetry axis.