Molecular scaffolds represent the core structures of molecules, obtained by removing side chains and replacing specific functional groups. For scaffold-based partitioning, the MurckoScaffold function from the RDKit library was utilized to extract the structural backbone of each molecule. In strict partitioning schemes within the 5CV framework, data were split such that molecules with the same SMILES or scaffold structures were not present in both training and validation sets. To eliminate stereochemical redundancy in the unique SMILES-based partitioning, canonical SMILES representations were used. This ensured that stereoisomers-compounds with similar solubility values were consistently placed in the same fold, preventing potential data leakage across subsets.