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

Area of Science:

• Chemical informatics
• Computational chemistry
• Cheminformatics

Background:

• Tautomerism is a fundamental chemical concept involving the interconversion of isomers.
• Existing chemical structure databases and identifiers like InChI have limitations in fully representing tautomeric forms.
• The International Union of Pure and Applied Chemistry (IUPAC) InChI Project aims to improve tautomer handling in chemical identifiers.

Purpose of the Study:

• To collect and analyze a comprehensive set of tautomeric interconversion rules.
• To evaluate the impact of these rules on chemical databases and the InChI standard.
• To inform the redesign of tautomerism handling for future InChI versions.

Main Methods:

• Compilation of 86 tautomeric interconversion rules from experimental literature and the CACTVS toolkit.
• Analysis of rule occurrence, overlap, and coverage against nine large chemical databases (over 400 million structures).
• Evaluation of tautomer set recapitulation by InChI V.1.05 (Standard and Nonstandard versions with 15T and KET options).

Main Results:

• The 86 rules encompass prototropic, ring-chain, and valence tautomerism.
• Analysis revealed occurrence rates, overlaps, and InChI recapitulation capabilities of the rules.
• Applying these rules could potentially triple the number of compounds affected by tautomerism in databases using InChI V2.

Conclusions:

• The developed set of tautomerism rules provides a significant expansion over current methods.
• These rules are crucial for improving the accuracy and completeness of chemical structure representation in informatics.
• The findings directly contribute to the IUPAC InChI Project's goal of enhancing tautomer handling in InChI V2.