Rimantadine, a chiral, cationic molecule, has a large hydrophobic adamantyl moiety, which fills the hydrophobic β-CD cavity more completely than does methylcyclohexanol. Accordingly, the binding free energies of rimantidine across β-CD and the β-CD derivatives are 1 to 10 kJ/mol more favorable than those of methylcyclohexanol for the same host molecules. Note that our results for this guest with native β-CD agree well with prior measurements reporting a binding free energy of -26.4 ± 0.08 kJ/mol . Perhaps unexpectedly, this cationic guest does not bind more strongly to CD derivatives with anionic substituents, such as MGLab 8, 9, and 23, than it does to native β-CD. However, the cationic MGLab 19 host does show the weakest binding to rimantidine. Possibly the clearest trend in this series is that binding of rimantidine to hosts with substituents on the secondary face is about 10 kJ/mol weaker than binding to hosts with derivatives on the primary face. This is similar to, but stronger than, the corresponding trend for guest methylcyclohexanol (Section 4.1.1).