We show in the file reaction-center.xml (supplementary material ZIP file) the reaction center of a wellknown substitution reaction (Fig. ) , . In this notation we show bonds that are made (in-bonds) as lines with an oval in the center, and bonds that are broken (out-bonds) as lines with a double line as in a strike-through, the notation which was first used by Fujita . We also show partial charges as full charges. In a more mechanistic representation, the made bond might be shown as a dotted arrow indicating the nucleophile attack and the broken bond as a wedge indicating the electronegativity of the chlorine atom. Different ways of using, or extending, features of molfiles for indicating reaction center features are possible. Two of the authors (GS and WI) maintain their own molfile drawing code and adding these features would not be overly hard. Of course, this entails the risk that such molfiles cannot be parsed successfully by other software. As in the enzyme example, the intermediate structures can be connected to the reactants with Chemical Structure Connection Points and Chemical Structure Substitution bonds. As in the amino acid connection points and substitution, we use InChI atom numbers to reference to these connection points. In case of a linear chain, it is simple to connect to the left and right side of each chain link. For random polymers this had already been extended to cover ladder polymers and branched polymers. Now we have extended the specification to allow for general structure substitution by specifying insertion points: The meaning of these positionNumbers is as follows: The Chemical Structure Connection Points moiety reference InChI atom numbers in the intermediate structure (the preceding molfile under the parent XML element). The first bond/positionNumber is again the ordinal number of the connection points moiety to be perfectly consistent with how this is done for proteins, nucleic acids and random polymers. The remaining bond/positionNumbers are the InChI atom numbers of the atoms in the distalMoiety structure which correspond to the connection points atoms in the intermediate structure. It is a kind of atom mapping, but not by enumerating all atoms but using an algorithm that allows a concise specification of a minimal set of atoms which "cut" a "hole" into the original structure into which the substituent structure is then inserted. That is why we call them "cut point atoms".