The ability of biological membranes to subdivide space in an aqueous environment with semipermeable barriers is one of the most crucial functions within living systems. The phospholipid bilayer is impermeable to ions and large polar molecules. The permeability of the membrane for a substance is proportional to its solubility in a nonpolar solvent relative to its solubility in water. In order to cross the membrane, the substance must separate from its solvation shell of water molecules (internal energy increase), then dissolve in the nonpolar core of the membrane (internal energy decrease), and finally, diffuse to the other side of the membrane and redissolve in water. It is the transition to the interior of the membrane that determines the possibility of meaningful permeability of the substance. For an ion or polar molecule, the change from solvation by water to the nonpolar surroundings represents a large increase in electrostatic potential energy (internal energy, enthalpy, free energy), and so there will exist a high barrier of activation energy making this transition extremely slow for such molecules and ions.