Binding constants for the GDCC dataset were measured in 10 mM sodium phosphate buffer at pH 11.5 ± 0.1. Binding measurements were done by ITC or NMR. In general, binding determination was carried out in triplicate using ITC, and the affinity constants ( ) and binding enthalpies (Δ ) were extracted and used to derive Δ and -Δ . NMR was used for very weak binders and Δ was extracted from . Binding of one guest (G3) to TEETOA was undetectable by ITC and NMR. To eliminate any neutralization contributions to Δ , attempts were made to ensure all solution concentrations for each experiment were within ±0.05 of tolerance. For each experiment, fresh solutions of host and guest were used to gather the data. In addition, waters of hydration are determined by qNMR using sodium ethanesulfonate as the water soluble internal standard of a known precise concentration. This standard will ensure the highest accuracy of host solution concentration and avoid misfits from concentration errors. For more details on GDCC experimental measurements, readers are advised to refer to the experimental literature.