Molecular Interactions and Inclusion Phenomena in Substituted beta-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 beta-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 beta-CD molecule together with solute-solvent (H2O) interactions have been represented by averaging structures of MD calculations for beta-CD alone and beta-CD surrounded by 133 H2O molecules. The effect of various substitutions of beta-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 beta-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 BCDs. 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 beta-CD ring cavity and in most of the studied substituted beta-CDs and shows maximum positive or negative values outside of the cavity, near the ring faces. Substitution of beta-CD by neutral substituents leads to enhanced binding of hydrophobic probes and significant changes in the MEP profile along the beta-CD symmetry axis.