It is worthwhile noting that the polar hydrogen atom we have parameterized is a main contributor to the more hydrophilic character of partially fluorinated methane relative to either CF 4 or CH 4 , as becomes obvious by inspecting SI Tables and. This effect of the polar hydrogen partially explains why the proportionality between surface area and hydration free energy no longer stands for partially fluorinated methane derivatives: each of the methane derivatives in SI Table has a higher surface area than CH 4 while having a much lower hydration free energy (the hydration free energy of methane is 2.549 kcal mol 1 ; see SI Table ). In addition, the non-uniform charge distribution in the partially fluorinated molecules also increases the hydrophilicity of these molecules relative to CH 4 or CF 4 .