The Need for a New Generation of Substructure Searching Software

Advances in synthetic chemistry mean that the molecules now synthesized include increasingly complex entities with mechanical bonds or extensive frameworks. For these complex molecular and supramolecular species, single-crystal X-ray crystallography has proved to be the optimal technique for determining full three-dimensional structures in the solid state. These structures are curated and placed in structural databases, the most comprehensive of which (for organic and metallo-organic structures) is the Cambridge Structural Database (CSD). A question of increasing importance is how users can search such databases effectively for these structures. In this Opinion we highlight some of the classes of complex molecules and supramolecules and the challenges associated with searching for them. We develop the idea of substructure searches that involve topological searches as well as searches for molecular fragments, and propose significant enhancements to substructure-search programs that are both achievable and highly beneficial for both the database user community and the broader chemistry community.