Computational Electrosynthesis: A Perspective on Mechanistic Questions, Methodological Approaches, and Elucidating...

In this perspective, we discuss how modern computational chemistry techniques are utilized to elucidate electrosynthesis reaction mechanisms via the computation of kinetic rate parameters that depend on reaction conditions. The specific focus is on elementary reaction steps that occur within the electrical double layer (EDL) environment at the working electrode/electrolyte interface, for which the governing free energy profiles and rate constants can be explicitly computed from classical molecular dynamics and hybrid quantum mechanics/molecular mechanics (QM/MM) computer simulations with atomistic resolution of the EDL environment. We focus on direct electrolysis reactions at inert electrodes with prototypical "E-C-E" mechanisms, in which the reaction yield and selectivity may depend on whether the full process occurs heterogeneously within the EDL, or rather the steps following the initial electron transfer proceed homogeneously with the second electron transfer occurring via disproportionation (DISP pathway). For short-lived radical intermediates with lifetimes of ∼10^-10-10^-7 s, branching between heterogeneous E-C-E and homogeneous DISP pathways is dictated by rate constants for substrate/intermediate desorption from the electrode surface (e.g., k _D ∼ 10⁷-10¹⁰ s^-1), which are difficult to determine experimentally but can be computed from molecular dynamics simulations. We discuss how strong solvophobic forces within electrolytes lead to significant association free energies between electrogenerated radical ion intermediates and the working electrode surface, resulting in residence times within the EDL that are on par with time constants of fast radical ion reactions. For electrosynthesis reactions that proceed entirely heterogeneously, the EDL environment can substantially modulate the reaction kinetics via electrostatic, solvophobic, and steric forces. We present several case studies highlighting modulated reaction kinetics within the EDL for nucleophilic coupling and deprotonation reactions of cation radical intermediates in anodic electrosynthesis. We expect that computational techniques will play an increasingly valuable role in optimizing electrosynthesis reactions via mechanistic descriptions of how key kinetic rate parameters are modulated by electrochemical reaction conditions.