The objective function was observed to decrease by 50-70% for each of the four optimizations performed, indicating improvements against the training set in all cases (see Supporting Information Section 2.1). This improvement was achieved with relatively small changes in the target parameters, as most of the refitted parameters changed only slightly from their initial values, varying less than 5% in most cases (Figure ). A notable exception is for [#1:1]-[#6X4] (hydrogen attached to tetravalent carbon), which changes up to 40% depending on the optimization. We also note that the for [#8X2H1+0:1] (hydroxyl oxygen) changes much more when trained against mixture data (-0.4 % for "pure only" vs. -1.7-2.8% for sets containing mixture data). One notable difference between the "pure only" set and the sets containing mixtures is the [#8X2H1+0:1] (hydroxyl oxygen) parameter, which is reduced by only 0.4% in the "pure only" (orange) set, but reduced by 1.7-2.8% in the other sets.