An overview of the proposed workflow for the different implicit-solvent models is provided in Fig. . For all compounds, the starting structure (details given in Sec. 4.1.1 and Sec. 4.1.2 below) was optimized with SMD using ORCA with the OPT keyword. The free energies of the optimized conformer were calculated with SMD using the Freq keyword. The free energies for openCOSMO-RS were calculated by adding the free energy of the given conformer in vacuum (obtained with the Freq keyword) to the solvation free energy calculated with openCOSMO-RS.