5.10: Interacting with Water

We get an idea of the hydrophilic, hydrophobic, and amphipathic nature of molecules when we try to dissolve them in water. Molecules like sugars (carbohydrates), alcohols, and most amino acids are primarily hydrophilic, they dissolve readily in water. Molecules like fats are highly hydrophobic; they do not dissolve significantly in water. Why the difference? To answer this question we have to be clear about what we mean when we say that a molecule is soluble in water. We consider this from two perspectives. The first is what the solution looks like at the molecular level, the second is how the solution behaves over time. Consider what pure water looks like. Because of its ability to make multiple H-bond-type electrostatic interactions in a tetrahedral arrangement, water molecules form a dynamic three-dimensional intermolecular interaction network. In liquid water the H-bond mediated interactions between the molecules break and form rapidly.

To insert a molecule A, known as a solute, into this network you have to break some of the H-bonds between the water (solvent) molecules. If the A molecules can make H-bonds with water molecules, that is, if they are hydrophilic, then there is little net effect on the free energy of the system. One H-bond is replaced by another. Such a molecule is soluble in water. So what determines how soluble the solute is? As a first order estimate, each solute molecule will have at least one layer of water molecules around it, otherwise it will be interacting with other solute molecules. If the number of the interacting solute molecules is large enough, the solute will no longer be in solution, but associated with itself. Small aggregates of solute molecules can, when small enough, remain suspended in the solution, a situation known as a colloid. The cytoplasm of a cell behaves like a colloid in many ways. While a solution consists of individual solute molecules surrounded by solvent molecules, the cytoplasm has molecules in solution and colloidal states of varying stability.^[229]

Now consider the behavior of hydrophobic solute molecules. Such molecules cannot make H-bonds with water molecules, so when inserted into water the total number of H-bond-type electrostatic interactions per unit volume decreases - the energy of the system increases (remember, bond forming lowers potential energy). Much of this “enthalpy” change, indicated as ΔH, is compensated for by LDF-interactions between the molecules. Generally, the net enthalpic effect is small. Something else must be going on to explain the insolubility of such molecules.

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