In this work, the free energy for each species optimized by SMD/M06-2X/BS1 in solution was calculated using the formula: G = E(BS2) + G(BS1) -E(BS1) + ∆G 1atm→1M ; where ∆G 1atm→1M = 1.89 kcal/mol is the free-energy change for compression of 1 mole of an ideal gas from 1 atm to the 1 M solution phase standard state. Natural population analysis (NPA) was carried out using NBO6 software integrated into Gaussian 16. The free energy barriers for ligand dissociation via TS19-20, TS34-35, TS18-20 and TS19-22-OMe were estimated according to the protocol presented by Hall and Hartwig. In this protocol, for example, the Gibbs free energy barrier for a dissociation reaction such as A-B → A + B is estimated as ΔG ⧧ ≈ ΔH = HA + HB -HA-B.