Heuristics-Guided Exploration of Reaction Mechanisms

TL;DR

This paper introduces an automated, heuristic-guided computational protocol for constructing and analyzing complex chemical reaction networks, enabling efficient exploration of reaction mechanisms with minimal manual intervention.

Contribution

The authors develop a parallelized, automated method that generates and optimizes reactive intermediates, detects related pairs, and searches for transition states to elucidate reaction pathways.

Findings

Successfully applied to Schrock catalyst for ammonia synthesis

Automated network visualization aids in mechanism analysis

Protocol reduces manual effort in complex reaction network exploration

Abstract

For the investigation of chemical reaction networks, the efficient and accurate determination of all relevant intermediates and elementary reactions is mandatory. The complexity of such a network may grow rapidly, in particular if reactive species are involved that might cause a myriad of side reactions. Without automation, a complete investigation of complex reaction mechanisms is tedious and possibly unfeasible. Therefore, only the expected dominant reaction paths of a chemical reaction network (e.g., a catalytic cycle or an enzymatic cascade) are usually explored in practice. Here, we present a computational protocol that constructs such networks in a parallelized and automated manner. Molecular structures of reactive complexes are generated based on heuristic rules derived from conceptual electronic-structure theory and subsequently optimized by quantum chemical methods to produce stable intermediates of an emerging reaction network. Pairs of intermediates in this network that might be related by an elementary reaction according to some structural similarity measure are then automatically detected and subjected to an automated search for the connecting transition state. The results are visualized as an automatically generated network graph, from which a comprehensive picture of the mechanism of a complex chemical process can be obtained that greatly facilitates the analysis of the whole network. We apply our protocol to the Schrock dinitrogen-fixation catalyst to study alternative pathways of catalytic ammonia production.