title: Modelling Chemical Reasoning to Predict and Invent Reactions.
abstract: The ability to reason beyond established knowledge allows organic chemists to solve synthetic problems and invent novel transformations. Herein, we propose a model that mimics chemical reasoning, and formalises reaction prediction as finding missing links in a knowledge graph. We have constructed a knowledge graph containing 14.4 million molecules and 8.2 million binary reactions, which represents the bulk of all chemical reactions ever published in the scientific literature. Our model outperforms a rule-based expert system in the reaction prediction task for 180 000 randomly selected binary reactions. The data-driven model generalises even beyond known reaction types, and is thus capable of effectively (re-)discovering novel transformations (even including transition metal-catalysed reactions). Our model enables computers to infer hypotheses about reactivity and reactions by only considering the intrinsic local structure of the graph and because each single reaction prediction is typically achieved in a sub-second time frame, the model can be used as a high-throughput generator of reaction hypotheses for reaction discovery.
authors.affiliation: Institute of Organic Chemistry and Center for Multiscale Theory and Computation, Westfälische Wilhelms-Universität Münster, Corrensstraße 40, 48149, Münster, Germany.
authors.forename: Marwin H S
authors.initials: MHS
authors.lastname: Segler
authors.affiliation: Institute of Organic Chemistry and Center for Multiscale Theory and Computation, Westfälische Wilhelms-Universität Münster, Corrensstraße 40, 48149, Münster, Germany.|Department of Physics and International Centre for Quantum and Molecular Structures, Shanghai University, Shangda Road 99, 200444, Shanghai, P.R. China.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Waller
keywords: artificial intelligence; augmented scientific discovery; computational chemistry; graph theory; organic chemistry