This value is in very good agreement with the experimental values from two independent NMR studies, 15.3 ± 0.4 kcal/mol 40 and 15.2 ± 0.2 kcal/mol. The reaction mechanism of the ligand exchange is illustrated in detail by the representative snapshots in Fig. . The solvent association proceeds via the formation of a square pyramid, where the axial Pd-N bond shortens as the system approaches the TS region, while one of the equatorial Pd-N bonds progressively elongates. This process leads to the formation of a trigonal bipyramidal TS, with an equal length of two Pd-N bonds involved in the ligand exchange. Taken together, the PMF from the US simulations confirms the associative nature of the ligand exchange mechanism. Furthermore, the activation barrier is in excellent agreement with the experimental values, supporting the notion that the MACE potential fitted to the hybrid DFT reference accurately describes the PES of the system and allows for a realistic description of the dynamics of the ligand exchange process.