title: Enumeration of ring-chain tautomers based on SMIRKS rules.
abstract: A compound exhibits (prototropic) tautomerism if it can be represented by two or more structures that are related by a formal intramolecular movement of a hydrogen atom from one heavy atom position to another. When the movement of the proton is accompanied by the opening or closing of a ring it is called ring-chain tautomerism. This type of tautomerism is well observed in carbohydrates, but it also occurs in other molecules such as warfarin. In this work, we present an approach that allows for the generation of all ring-chain tautomers of a given chemical structure. Based on Baldwin's Rules estimating the likelihood of ring closure reactions to occur, we have defined a set of transform rules covering the majority of ring-chain tautomerism cases. The rules automatically detect substructures in a given compound that can undergo a ring-chain tautomeric transformation. Each transformation is encoded in SMIRKS line notation. All work was implemented in the chemoinformatics toolkit CACTVS. We report on the application of our ring-chain tautomerism rules to a large database of commercially available screening samples in order to identify ring-chain tautomers.
authors.affiliation: Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick National Laboratory for Cancer Research , Frederick, Maryland 21702, United States.
authors.forename: Laura
authors.initials: L
authors.lastname: Guasch
authors.forename: Markus
authors.initials: M
authors.lastname: Sitzmann
authors.forename: Marc C
authors.initials: MC
authors.lastname: Nicklaus
mesh_terms: D003500:Cyclization; D062126:Databases, Chemical; D008968:Molecular Conformation