<p>We
have collected 86 different transforms of tautomeric interconversions. Out of
those, 54 are for prototropic (non-ring-chain) tautomerism; 21 for ring-chain
tautomerism; and 11 for valence tautomerism. The majority of these rules have
been extracted from experimental literature. Twenty rules – covering the most
well-known types of tautomerism such as keto-enol tautomerism – were taken from
the default handling of tautomerism by the chemoinformatics toolkit CACTVS. The
rules were analyzed against nine differerent databases totaling over 400
million (non-unique) structures as to their occurrence rates, mutual overlap in
coverage, and recapitulation of the rules’ enumerated tautomer sets by InChI
V.1.05, both in InChI’s Standard and a Non-Standard version with the increased
tautomer-handling options 15T and KET turned on. These results and the
background of this study are discussed in the context of the IUPAC InChI
Project tasked with the redesign of handling of tautomerism for an InChI version
2. Applying the rules presented in this paper would approximately triple the
number of compounds in typical small-molecule databases that would be affected
by tautomeric interconversion by InChI V2. A web tool has been created to test these rules
at https://cactus.nci.nih.gov/tautomerizer.</p>
