Benchmarking a foundation potential against quantum chemistry methods for predicting molecular redox potentials

Abstract: Computational high-throughput virtual screening is essential for identifying redox-active molecules for sustainable applications such as electrochemical carbon capture. A primary challenge in this approach is the high computational cost associated with accurate quantum chemistry calculations. Machine learning foundation potentials (FPs) trained on extensive density functional theory (DFT) calculations offer a computationally efficient alternative. Here, we benchmark the MACE-OMol-0 FP against a hierarchy of DFT functionals for predicting experimental molecular redox potentials for both electron transfer (ET) and proton-coupled electron transfer (PCET) reactions. We find that MACE-OMol achieves exceptional accuracy for PCET processes, rivaling its target DFT method. However, its performance is diminished for ET reactions, particularly for multi-electron transfers involving reactive ions that are underrepresented in the OMol25 training data, revealing a key out-of-distribution limitation. To overcome this, we propose an optimal hybrid workflow that uses the FP for efficient geometry optimization and thermochemical analysis, followed by a crucial single-point DFT energy refinement and an implicit solvation correction. This pragmatic approach provides a robust and scalable strategy for accelerating high-throughput virtual screening in sustainable chemistry.