Fig. 2.

Thermodynamic cycle for $logD$ calculation. First the atoms’ partial charges are turned off retrieving $\mathrm{\Delta }{G}_{\mathrm{w}}^{\mathrm{elec}}$, $\mathrm{\Delta }{G}_{\mathrm{vac}}^{\mathrm{elec}}$ and $\mathrm{\Delta }{G}_{\mathrm{cyc}}^{\mathrm{elec}}$ in water, vacuum and cyclohexane phase respectively. This step is referred to as the ’discharging step’ in the main text. Then, van der Waals terms are switched off and $\mathrm{\Delta }{G}_{\mathrm{w}}^{\mathrm{vdW}}$, $\mathrm{\Delta }{G}_{\mathrm{vac}}^{\mathrm{vdW}}$ and $\mathrm{\Delta }{G}_{\mathrm{cyc}}^{\mathrm{vdW}}$ are calculated in each phase. This step is referred to as the ’vanishing step’ in the main text. The diagram assumes no change in protonation state between solvated and vacuum phases