In developing a dataset for SAMPL9, which is the focus of a themed Collection of Physical Chemistry chemical Physics, we sought to collect guests having drug-like structures that would survey structureactivity relationships (SARs) analogous to those typically developed by medicinal chemists engaged in targeted drug discovery projects, and that would include some with reasonably strong affinities for the CDs. This is not a trivial task, as CDs bind most guests in a rather narrow band of rather modest affinities . One survey of over 1200 available experimental CD-guest binding free energies reported a mean of -14.6 kJ/mol with standard deviation 5.9 kJ/mol . Because the adamantyl derivatives rimantidine and amantadine are known to bind βCD with good affinity , we initially tested purchasable adamantane derivatives, but these were not sufficiently water-soluble. Other compound series that also possess a hydrophobic moiety to drive binding and a polar moiety to drive solubility also failed to combine both attributes. We then found that βCD bound a phenothiazine drug with good affinity, so we procured and tested phenothiazines and chemically similar drugs and found that virtually all have favorable solubilities and CD affinities. These observations, combined with the ongoing clinical relevance of the phenothiazines and the fact that the phenothiazines would be new to SAMPL, motivated us to use them as the basis of the present challenge. The phenothiazines chosen here are listed in Table .