Graph-Driven Reaction Discovery: Progress, Challenges, and Future Opportunities

[Image: see text] Graph-based descriptors, such as bond-order matrices and adjacency matrices, offer a simple and compact way of categorizing molecular structures; furthermore, such descriptors can be readily used to catalog chemical reactions (i.e., bond-making and -breaking). As such, a number of graph-based methodologies have been developed with the goal of automating the process of generating chemical reaction network models describing the possible mechanistic chemistry in a given set of reactant species. Here, we outline the evolution of these graph-based reaction discovery schemes, with particular emphasis on more recent methods incorporating graph-based methods with semiempirical and ab initio electronic structure calculations, minimum-energy path refinements, and transition state searches. Using representative examples from homogeneous catalysis and interstellar chemistry, we highlight how these schemes increasingly act as “virtual reaction vessels” for interrogating mechanistic questions. Finally, we highlight where challenges remain, including issues of chemical accuracy and calculation speeds, as well as the inherent challenge of dealing with the vast size of accessible chemical reaction space.