(427b) Linear Free Energy Relationships for Molecular Catalysts: Promise or Pipe Dream?

The field of heterogenous catalysis has made remarkable progress owing to the development of theoretical foundations and design principles based on frameworks such as scaling relationships. Molecular or homogeneous catalysis is yet to leverage the power of theoretically developed design frameworks on account of challenges associated with treatment of transition metal-based active centers, poor understanding of underlying mechanisms, and ligand/solvent/counterion effects that are challenging to characterize. We develop a computational approach, inspired by the Taft equation in organic chemistry, to construct active site-dependent linear free energy relationships (LFERs) for transition metal complexes. The framework captures both electronic and steric ligand effects using a combination of the activation strain model and energy decomposition analysis (EDA). Using CH activation with enzyme-inspired copper-oxygen complexes as the model chemistry, we demonstrate that a combination of Sterimol parameters and ligand bite angles are suitable descriptors to construct an LFER for capturing geometric (or strain) effects of steric factors. Although we show that mapping electronic effects enables direct comparison with experiments to deduce reaction mechanisms, the development of LFERs will require suitable electronic descriptors. We are currently employing EDA to develop quantitative Hammett-like descriptors for arbitrary ligands. The quantitative nature of this analysis enables precise assignments of descriptors, accurate prediction of mechanism sensitivity to electronic and structural attributes, and identification of factors responsible for deviations from linearity. We therefore believe that a structured approach to rational design and screening of transition metal complex catalysts is a viable proposition.