Optional guests were those for which experimental data was already available. In addition, one very poorly performing CD ranked method was not included in much of our analysis because its performance was so poor that it would have made most other methods appear virtually identical, but was included in the non-ranked analysis and in All quantities are reported as point estimate ± statistical error from the ITC data fitting procedure. The upper bound (1%) was used for errors reported to be < 1%. We also included a 3% relative uncertainty in the titrant concentration assuming the stoichiometry coefficient to be fitted to the ITC data for the Isaacs (TrimerTrip) and Gilson (cyclodextrin derivatives) datasets, where concentration error had not been factored in to the original error estimates. For the OA/exo-OA sets, provided uncertainties already included concentration error. In some cases, exoOA-g1 binding constants were not detected (ND) by ITC or H NMR. Binding of guest g2 to exoOA was very weak so only H NMR spectroscopy could produce reliable free energy data. The stoichiometry for each host-guest system is defined in ( ) Statistical errors were propagated from the measurements. ( ) All experiments were performed at 298 K. ( ) Units of M -2 . ( ) Units of M -3 .