Using the hydrogen evolution reaction (HER) as a prototypical case, this study analyses the limitations of current first-principles approaches, particularly those based on the computational hydrogen electrode (CHE), for predicting single-atom catalyst (SAC) activity, identifying factors such as the sensitivity of reaction thermodynamics to the local atomic environment, the often-unknown experimental structure of SACs, neglected SAC-specific reaction intermediates, solvent effects, catalyst evolution under operating conditions, material instability, and intrinsic density functional theory approximations as sources of discrepancy between theory and experiment, and proposing that integrating these chemical complexities and uncertainties, potentially through artificial intelligence and data-dr
Using the hydrogen evolution reaction (HER) as a prototypical case, this study analyses the limitations of current first-principles approaches, particularly those based on the computational hydrogen electrode (CHE), for predicting single-atom catalyst (SAC) activity, identifying factors such as the sensitivity of reaction thermodynamics to the local atomic environment, the often-unknown experimental structure of SACs, neglected SAC-specific reaction intermediates, solvent effects, catalyst evolution under operating conditions, material instability, and intrinsic density functional theory approximations as sources of discrepancy between theory and experiment, and proposing that integrating these chemical complexities and uncertainties, potentially through artificial intelligence and data-dr