Accurately Predicting Barrier Heights for Radical Reactions in Solution Using Deep Graph Networks

Quantitative estimates of reaction barriers and solvent effects are essential for developing kinetic mechanisms and predicting reaction outcomes. Here, we create a new data set of 5,600 unique elementary radical reactions calculated using the M06-2X/def2-QZVP//B3LYP-D3(BJ)/def2-TZVP level of theory. A conformer search is done for each species using TPSS/def2-TZVP. Gibbs free energies of activation and of reaction for these radical reactions in 40 common solvents are obtained using COSMO-RS for solvation effects. These balanced reactions involve the elements H, C, N, O, and S, contain up to 19 heavy atoms, and have atom-mapped SMILES. All transition states are verified by an intrinsic reaction coordinate calculation. We next train a deep graph network to directly estimate the Gibbs free energy of activation and of reaction in both gas and solution phases using only the atom-mapped SMILES of the reactant and product and the SMILES of the solvent. This simple input representation avoids computationally expensive optimizations for the reactant, transition state, and product structures during inference, making our model well-suited for high-throughput predictive chemistry and quickly providing information for (retro-)synthesis planning tools. To properly measure model performance, we report results on both interpolative and extrapolative data splits and also compare to several baseline models. During training and testing, the data set is augmented by including the reverse direction of each reaction and variants with different resonance structures. After data augmentation, we have around 2 million entries to train the model, which achieves a testing set mean absolute error of 1.16 kcal mol^–1 for the Gibbs free energy of activation in solution. We anticipate this model will accelerate predictions for high-throughput screening to quickly identify relevant reactions in solution, and our data set will serve as a benchmark for future studies.