Fast and automated identification of reactions with low barriers using meta-MD simulations

Abstract

We test our meta-molecular dynamics (MD) based approach for finding low-barrier (<30 kcal/mol) reactions (SciPost Chem. 2021, 1, 003) on uni- and bimolecular reactions extracted from the barrier dataset developed by Grambow et al. (Scientific Data 2020, 7, 137). For unimolecular reactions the meta-MD simulations identify 25 of the 26 products found by Grambow et al., while the subsequent semiempirical screening eliminates an additional four reactions due to at an overestimation of the reaction energies or estimated barrier heights relative to DFT. In addition, our approach identifies an additional 36 reactions not found by Grambow et al., 10 of which are <30 kcal/mol. For bimolecular reactions the meta-MD simulations identify 19 of the 20 reactions found by Grambow et al., while the subsequent semiempirical screening eliminates an additional reaction. In addition, we find 34 new low-barrier reactions. For bimolecular reactions we found that it is necessary to ”encourage” the reactants to go to previously undiscovered products, by including products found by other MD simulations when computing the biasing potential as well as decreasing the size of the molecular cavity in which the MD occurs, until a reaction is observed. We also show that our methodology can find the correct products for two reactions that are more representative of those encountered in synthetic organic chemistry. The meta-MD hyperparameters used in this study thus appears to be generally applicable to finding low-barrier reactions.