Organic Chemistry

Module 1. Hydrogen bond and hydrophobic interaction

Lesson 3
ELEMENTARY IDEA OF HYDROPHOBICITY, HYDROPHOBIC INTERACTIONS AND ITS IMPORTANCE IN THE STRUCTURE OF PROTEINS

3.1 Introduction

When you add some drops of oil to water, the drops combine to form a larger drop. This comes about because water molecules are attracted to each other and are cohesive because they are polar molecules. Oil molecules are non polar and thus have no charged regions on them. This means that they are neither repelled nor attracted to each other. The attractiveness of the water molecules for each other then has the effect of squeezing the oil drops together to form a larger drop. Since it looks like the oil molecules are avoiding the water, this type of interaction is called a hydrophobic interaction. Hydrophobic interaction is an effective interaction between two nonpolar molecules that tend to avoid water and, as a result, prefer to cluster around each other.

Hydrophobic interactions describe the relations between water and hydrophobes (low water-soluble molecules). Hydrophobes are nonpolar molecules and usually have a long chain of carbons that do not interact with water molecules. The mixing of fat and water is a good example of this particular interaction. The common misconception is that water and fat doesn’t mix because the Van der Waals forces that are acting upon both water and fat molecules are too weak. However, this is not the case. The behavior of a fat droplet in water has more to do with the enthalpy and entropy of the reaction than its intermolecular forces.

Hydrophobic interactions along with hydrophilic interactions help to determine the three dimensional shape of biologically important molecules and structures such as proteins and cell membranes.

Nonpolar molecules are not good acceptors of the hydrogen bond. When a nonpolar molecule is placed in water, the hydrogen bonding network of water is disrupted. The water molecules therefore reorganize around the solute and make a sort of cage, similar to the structure of water in ice, in order to gain back the broken hydrogen bonds. This reorganization results in a considerable loss in the configurational entropy of water and therefore an increase in the free energy.

If there are two or more such nonpolar molecules, the configuration in which they are spatially together (clustered together) is preferred because now the hydrogen bonding network of water is disrupted in one (albeit bigger) pocket, rather than in several small pockets. Therefore, the entropy of water is larger when the nonpolar molecules are clustered together, leading to a decrease in the free energy.

The hydrophobic interaction is entropy-driven and thus intrinsically temperature sensitive. For instance, the solubility of methane in water decreases with increasing temperature at low temperatures (after reaching a minimum at about 350 K, the solubility increases with higher temperature). In liquid water, a single water molecule can form four hydrogen bonds with nearby water molecules. However, around an apolar solute, surrounding waters can not form hydrogen bonds with it. Therefore the orientation of waters near the hydrophobic solute is more ordered and the entropy of the system is reduced. For this reason, apolar solutes tend to be lumped together to minimize the number of waters affected by them.

3.2 Causes of Hydrophobic Interactions

American chemist Walter Kauzmann discovered that nonpolar substances like fat molecules tend to clump up together rather than distributing itself in a water medium, because this allow the fat molecules to have minimal contact with water.

When a hydrophobe is dropped in an aqueous medium, hydrogen bonds between water molecules will be broken to make room for the hydrophobe; however, water molecules do not react with hydrophobe. This is considered an endothermic reaction, because when bonds are broken heat is put into the system. Water molecules that are distorted by the presence of the hydrophobe will make new hydrogen bonds and form an ice-like cage structure called a clathrate cage around the hydrophobe. This orientation makes the system (hydrophobe) more ordered. With a decrease in disorder, the entropy of the system decreases.

The change in enthalpy of the system can be negative, zero, or positive because the new hydrogen bonds can partially, completely, or over compensate for the hydrogen bonds broken by the entrance of the hydrophobe. The change in enthalpy, however, is insignificant in determining the spontaneity of the reaction (mixing of hydrophobic molecules and water) because the change in entropy is very large.

3.3 Strength of Hydrophobic Interactions

Hydrophobic interactions are relatively stronger than other weak intermolecular forces (i.e. Van der Waals interactions or Hydrogen bonds). The strength of hydrophobic interactions depends on following factors

1. Temperature

As temperature increases, the strength of hydrophobic interactions increases also. However, at an extreme temperature, hydrophobic interactions will denature.

2. Number of carbons on the hydrophobes

Molecules with the greatest number of carbons will have the strongest hydrophobic interactions.

3. The shape of the hydrophobes

Aliphatic organic molecules have stronger interactions than aromatic compounds. Branches on a carbon chain will reduce the hydrophobic effect of that molecule. This is so because carbon branches produce steric hindrance, so it is harder for two hydrophobes to have very close interactions with each other to minimize their contact to water. The linear carbon chain can produce the largest hydrophobic interaction.

3.4 Biological Importance of Hydrophobic Interactions

Hydrophobic Interactions are important for the folding of proteins. This is important in keeping a protein alive and biologically active, because it allow to the protein to decrease in surface area and reduce the undesirable interactions with water. Apart from proteins, there are many other biological substances that rely on hydrophobic interactions for its survival and functions, like the phospholipid bilayer membranes in every cell.