To generate a predicVve solubility model for the scrambled 3 3 :13 -R POC mixture, a dataset containing the previous solubility studies of the scrambled 3 3 :13 -R POC mixture in both convenVonal and size-excluded solvents was manually collated, and the resulVng 44 solvents categorised based on the overall solubility of the POC (Figure , Table ). To ensure a reliable predicVon method could be developed, the exisVng solubility data contained both poorly and highly solubilising molecules. This dataset was then used to predict the solubility sphere for the 3 3 :13 -R POC mixture using the HSPiP sobware (Figure ). Using this solubility sphere, there was an 84% success rate on correlaVng the solvents with the solute parameters (Table ), i.e., 84% of the solvents used to build the model would have been correctly predicted to solubilise the POC mixture. Furthermore, 86% of the known size-excluded solvents included in the model also correlated with the predicVons. While a reasonably good success rate, there may be several reasons why this is not higher: (i) we are applying the model to a staVsVcal distribuVon of a mixture of cage species instead of a single molecular species; (ii) the cage structure is quite complex, at least when compared to small molecules and polymers; and (iii) the dataset included size-excluded solvents, which do not solvate the enVre cage molecule (i.e., the cavity of the cage is unsolvated), although the predicVon accuracy is quite consistent between the full solvent dataset and just the size-excluded solvent dataset, potenVally suggesVng that the solvaVon state of the cage cavity is a less contribuVng factor. -R POC which meets all the selecIon criteria. These predicIons were validated experimentally -four candidates were idenIfied to be insoluble at the selected minimum 200 mg + 1 mL threshold (purple) and six candidates were idenIfied to be soluble at 200 mg + 1 mL (green). Each candidate is labelled with its Hansen interacIon radius.