Tautomers are compounds with identical molecular formulas, which are structural (i.e., constitutional) isomers of compounds that readily interconvert, often by proton migration, among other mechanisms . Many organic compounds containing conjugated bonds can be represented by multiple human-interpretable structures, though chemists often prefer one tautomeric representation. Compounds with unique anhydrous crystal structures often interconvert into multiple bonding states in solution, and even relatively simple compounds such as guanine (C 5 H 5 N 5 O), with completely defined core bonding, may have as many as 36 valid tautomeric representations . MØD treats different tautomeric forms as distinct chemical species; it was thus necessary to suppress the generation of multiple tautomeric forms for the same molecule. Tautomerism is generally acknowledged to be a difficult representational problem in computational chemistry (see ), although resolutions for this issue have been proposed (e.g., ). Tautomeric structures are capable of undergoing the same reactions because they are interconvertible, and denoting tautomers as unique in this context is meaningful in some ways (e.g., with respect to precise reaction mechanisms or hydrogen bonding), but not in others (e.g., the overall outcome of reactions). We handled tautomerism at the level of encoded reaction mechanisms, such that reaction schemes would provide tautomeric species that a chemist would recognize as "catalog representations" of tautomers , and such that only one unique tautomer of a given compound would be produced anywhere in the network, e.g., enol forms were forced into keto or aldo forms, and reaction mechanisms were built to infer the existence of transient reactive species such as enolates. This simplification of tautomers reduces the number of unique species representations generated, reducing computational cost and assisting in output interpretation.