Due to the presence of higher torsional barriers and because of a higher N , the HREM simulation of compound 2 in vacuo required a minimum of 12 replicas with a minimum scaling factor of s min = 0.1 to allows for at least one round trip on the average per replica during 16 ns of simulation (for a total invested HREM simulation of 192 ns). As for the case of compound 1, we launched two HREM simulations with and without acceptance ratio balancing according to Eq. 4 with the starting standard scaling protocol given by Eq. 3. In Figure of the SI, we show the flux (Eq.