Theoretical and Computational Chemistry

Toward a Comprehensive Treatment of Tautomerism in Chemoinformatics Including in InChI V2

Marc Nicklaus National Cancer Institute, NIH

Abstract

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.

Content

Thumbnail image of Tautomer_Rules_V6_MCN_2019-11-22.pdf
download asset Tautomer_Rules_V6_MCN_2019-11-22.pdf 1 MB [opens in a new tab]

Supplementary material

Thumbnail image of CACTVS Tcl scripts 2019-11-03.zip
download asset CACTVS Tcl scripts 2019-11-03.zip 0.03 MB [opens in a new tab]
CACTVS Tcl scripts 2019-11-03
Thumbnail image of S1.xlsx
download asset S1.xlsx 0.26 MB [opens in a new tab]
S1
Thumbnail image of S2.xlsx
download asset S2.xlsx 0.27 MB [opens in a new tab]
S2
Thumbnail image of S3.xlsx
download asset S3.xlsx 0.01 MB [opens in a new tab]
S3
Thumbnail image of S4.xlsx
download asset S4.xlsx 0.26 MB [opens in a new tab]
S4
Thumbnail image of S5.xlw
download asset S5.xlw 1 MB [opens in a new tab]
S5
Thumbnail image of Tauto Rules for InChI V2 2019-11-20_Supp_Inf.docx
download asset Tauto Rules for InChI V2 2019-11-20_Supp_Inf.docx 0.03 MB [opens in a new tab]
Tauto Rules for InChI V2 2019-11-20 Supp Inf

Supplementary weblinks