A framework for constructing linear free energy relationships to design molecular transition metal catalysts

Abstract

A computational framework for ligand-driven design of transition metal complexes is presented in this work. We propose a general procedure for the construction of active site-specific linear free energy relationships (LFERs), which are inspired from Hammett and Taft correlations in organic chemistry and grounded in the activation strain model (ASM). Ligand effects are isolated and quantified in terms of their contribution to interaction and strain energy components of ASM. Scalar descriptors that are easily obtainable are then employed to construct the complete LFER. We successfully demonstrate proof-of-concept by constructing and applying an LFER to CH activation with enzyme-inspired [Cu₂O₂]²⁺ complexes. The key benefit of using ASM is a built-in compensation or error cancellation between LFER prediction of interaction and strain terms, resulting in accurate barrier predictions for 37 of the 47 catalysts examined in this study. The LFER is also transferable with respect to level of theory and flexible towards the choice of reference system. The absence of interaction-strain compensation or poor model performance for the remaining systems is a consequence of the approximate nature of the chosen interaction energy descriptor and LFER construction of the strain term, which focuses largely on trends in substrate and not catalyst strain.