The Thermodynamics Integration (TI) method is employed to estimate the free energy cost to generate a soft cavity in four different solvent mediums. Here, the initial state is where zero solutesolvent interaction is present and in the final state the r -12 part of the solute is introduced. To do that the C6 and C12 terms for the van der Walls equation are set as zero for the solute at initial state and the final state only C12 is there. For all simulations in this context, the box size is around 4 nm. The numbers of water, urea, TMAO are presented in table II. To perform TI, 16-20 λ points are considered.