Machine Learning Accelerated Computational Design of Bio‐Inspired Catalysts in the Nitrogen Reduction Reaction

Abstract

ABSTRACT The development of efficient catalysts for nitrogen conversion to ammonia is critical for a sustainable alternative to the energy‐intensive Haber–Bosch process. Yet, rational catalyst design remains highly challenging, compounded by complex structure–function relationships within realistic conditions. Herein, we present an integrated computational framework combining quantum chemical calculations with 27 machine learning models to predict experimental catalytic metrics in metal–ligand complexes. The models are trained and validated on a large experimental database and demonstrate high predictive accuracy across multiple tasks. For classification, family 1 and family 2 catalysts achieved test accuracies up to 1. Regression models yield test R 2 values of 0.91 and 0.88 for turnover frequency (TOF) and turnover number (TON) predictions in family 1, and 0.96 and 0.99 in family 2. Notably, the models accurately capture time‐dependent variability of TOF and TON for new complexes, with predicted values closely matching experimental results. Moreover, strong transfer learning capability is observed for structurally distinct coordination architectures. Feature interpretation reveals clear design principles for optimal catalysts involving metal spin state, ligand geometry, charge distribution, and experimental conditions. Together, this study established an efficient and practical framework for discovery and inverse design of high‐performance catalysts under realistic conditions, with broader relevance to electrocatalysis.