Z-matrix template-based substitution approach for enumeration of 3D molecular structures

Abstract

The exhaustive enumeration of 3D chemical structures based on Z-matrix templates has recently been used in the quantum chemical investigation of constitutional isomers, diastereomers and rotamers. This simple yet powerful initial structure generation approach can apply beyond the investigation of compounds of identical formula by quantum chemical methods. This paper provides a comprehensive description of the overall concept followed by a practical tutorial to the approach.•The four steps required for Z-matrix template-based substitution are template construction, generation of tuples for substitution sites, removal of duplicate tuples and substitution on the template.•The generated tuples can be used to create chemical identifiers to query compound properties from chemical databases.•All of these steps are demonstrated in this paper by common model compounds and are very straightforward for an undergraduate audience to reproduce. A comparison of the approach in this paper and other options is also discussed.