Revisiting Textbook Azide-Clock Reactions: A “Propeller-Crawling” Mechanism Explains Differences in Rates

• DOI: 10.1021/jacs.4c03360
• Publication Date: 2024-04-30T13:39:48Z
• Authors: Anthony T. Bogetti; Matthew C. Zwier; Lillian T. Chong
• Keywords: Molecular machine; Reaction rate

An ongoing challenge to chemists is the analysis of pathways and kinetics for chemical reactions in solution, including transient structures between reactants products that are difficult resolve using laboratory experiments. Here, we enabled direct molecular dynamics simulations a textbook series on hundreds ns μs time scale weighted ensemble (WE) path sampling strategy with hybrid quantum mechanical/molecular mechanical (QM/MM) models. We focused azide-clock involving addition an azide anion each three long-lived trityl cations acetonitrile–water solvent mixture. Results reveal two-step mechanism: (1) diffusional collision form ion-pair intermediate; (2) "activation" or rearrangement intermediate product. Our yield not only reaction rates within error experiment but also individual steps, indicating activation step as rate-limiting all cations. Further, trend due dynamical effects, i.e., differing extents "crawling" along cation's phenyl-ring "propellers" during step. study demonstrates power analyzing gain insights mechanisms, underscoring value WE other related strategies modern toolbox chemists.