Our study is the first applicaVon of HSPs for POC solubility predicVon, obtaining an accuracy of 84% using the scrambled 3 3 :13 -R mixture and known solubility data. This approach is powerful considering the massive chemical space spanned by candidate solvents for PLs. While not an explicitly in silico method (i.e., the solubility sphere of the candidate POC must be calculated using experimental results), HSPs allow us to exploit the wealth of informaVon contained within oben sparse solubility datasets. Of the 10 candidate solvent molecules, 6 were soluble at the tested threshold concentraVon. This highlights one of the limitaVons of HSPs for PL solubility predicVon -this method mainly classifies solvents as soluble or insoluble. This classificaVon is largely determined by the concentraVon of the experimental solubility data that was used to calculate the solubility sphere and may not be representaVve of other target concentraVons.