Ultimately, though, we surmise that the most important single contribution to binding in these systems is the hydrophobic effect, given that the largely hydrophobic phenothiazine ring systems are sized well to fit into the hydrophobic CD binding cavity. This view is consistent with the trend to preserved and even improved binding by H26DM-βCD, which is more hydrophobic than native βCD. We conjecture that the sharp , across-the-board drop in affinity on going to the even more hydrophobic HTM-βCD traces to steric obstruction by the newly added methyl groups at the 3-hydroxyls.