When a tree or network is constructed, a crucial step is querying whether a scaffold is already part of it. This matching is done using SMILES representations of the scaffolds. The default setting is to use unique SMILES with aromaticity encoding but without stereochemical information. This can be adjusted, e.g. to include stereochemistry. Scaffold Generator generally retains given stereochemical information during scaffold creation and dissection by transferring the CDK IStereoElement objects to the newly created structures. But this only works if all defining elements of a stereo group, i.e. atoms and/or bonds, are still present in the generated substructures. Since in the majority of cases side chains define stereochemistry and stereochemical information is often not given or incomplete in molecular data sets, the consideration of given stereochemical information in tree or network construction is turned off per default as stated above. But it can be enabled for use cases where it is relevant (Figure ). Other molecular characteristics that can generally be taken into account or not (depending on the specific use case) for the determination of equivalence between two structures in cheminformatic analyses are tautomeric forms or protonation states, for example.