In total, 2000 equilibrium data points were collected from each λ -window during the production simulations, and free energies were estimated using MBAR . The AM1-BCC charging scheme, consistent with mainline OpenFF FFs (Parsley, Sage) was used via the OpenEye toolkit (2022.1.1) . The Lorentz-Berthelot combination rules were used to compute the interaction parameters be-tween two, unlike atoms. Constraints were placed on all bonds involving hydrogen and a long-range energy correction was used . Further computational details and convergence tests are available in Supporting Information Section S5.