To prevent data leakage, the MLIPs were tested on configurations of the substrate immersed in 56 solvent molecules, representing a slightly larger system not included in the training. These configurations were generated through four independent uphill MD simulations, resulting in a total of 1,004 configurations (Fig. ); further details can be found in SI §S4.1. Visualisation of the chemical space covered by this test set, using a multidimensional scaling (MDS) map with the smooth overlap of atomic positions (SOAP) descriptor, shows that it includes configurations across the PES, including RS, intermediates, and PS (Fig. ). The intermediate region is divided into two subregions, Inter1 and Inter2, based on the r LG Nu Using the trained MLIP, the mechanism of R3 was studied through WTMetaD, using as the collective variable (CV) the two coordination numbers (CN(r C 1 -O Nu ) and CN(r