HYDROPHOBIC INTERACTIONS: WHAT IS IT, IMPORTANCE AND EXAMPLES - BIOLOGY - 2025

The hydrophobic interactions (HI) are the forces that maintain the cohesion between apolar compounds immersed in a solution or polar solvent. Unlike other non-covalent interactions, such as hydrogen bonds, ionic interactions or van der Waals forces, hydrophobic interactions do not depend on the intrinsic properties of solutes, but rather on solvents.

A very illustrative example of these interactions can be the phase separation that occurs when it comes to mixing water with oil. In this case, the oil molecules "interact" with each other as a result of the arrangement of the water molecules around them.

Fat in water emulsion (Catrin Sohrabi, from Wikimedia Commons)

The notion of these interactions has existed since before the 1940s. However, the term "hydrophobic bond" was coined by Kauzmann in 1959, while studying the most important factors in stabilizing the three-dimensional structure of certain proteins.

HIs are one of the most important nonspecific interactions that take place in biological systems. They also play an important role in a wide variety of engineering applications and the chemical and pharmaceutical industry that we know today.

What are hydrophobic interactions?

The physical cause of IH is based on the inability of nonpolar substances to form hydrogen bonds with water molecules in a solution.

They are known as "nonspecific interactions" since they are not related to the affinity between solute molecules, but rather to the tendency of water molecules to maintain their own interactions through hydrogen bonding.

When in contact with water, apolar or hydrophobic molecules tend to aggregate spontaneously, in order to achieve the greatest stability by reducing the surface area of ​​contact with water.

This effect could be mistaken for a strong attraction, but it is only a consequence of the nonpolar character of the substances in relation to the solvent.

Explained from a thermodynamic point of view, these spontaneous associations occur in search of an energetically favorable state, where there is the least variation of free energy (∆ G).

Taking into account that ∆ G = ∆ H - T∆ S, the most energetically favorable state will be the one where the entropy (∆ S) is greater, that is, where there are fewer water molecules whose rotational and translational freedom is reduced by contact with an apolar solute.

When apolar molecules associate with each other, bound by water molecules, a more favorable state is obtained than if these molecules remained separate, each surrounded by a different "cage" of water molecules.

Biological importance

HIs are highly relevant since they occur in a variety of biochemical processes.

These processes include conformational changes in proteins, the binding of substrates to enzymes, the association of subunits of enzyme complexes, the aggregation and formation of biological membranes, the stabilization of proteins in aqueous solutions and others.

In quantitative terms, different authors have taken on the task of determining the importance of HI in the stability of the structure of a large number of proteins, concluding that these interactions contribute more than 50%.

Many membrane proteins (integral and peripheral) are associated with lipid bilayers thanks to HI when, in their structures, these proteins have hydrophobic domains. Furthermore, the stability of the tertiary structure of many soluble proteins is dependent on HI.

Some techniques in the study of Cell Biology exploit the property that some ionic detergents possess to form micelles, which are "hemispherical" structures of amphiphilic compounds whose apolar regions associate with each other thanks to HI.

Micelles are also used in pharmaceutical studies involving the delivery of fat-soluble drugs and their formation is also essential for the absorption of complex vitamins and lipids in the human body.

Examples of Hydrophobic Interactions

Membranes

An excellent example of HI is the formation of cell membranes. Such structures are composed of a phospholipid bilayer. Their organization is due to the HIs that occur between the apolar tails in "repulsion" to the surrounding aqueous medium.

Protein

HIs have a great influence on the folding of globular proteins, whose biologically active form is obtained after the establishment of a particular spatial configuration, governed by the presence of certain amino acid residues in the structure.

• The case for apomyoglobin

Apomyoglobin (myoglobin lacking the heme group) is a small alpha-helical protein that has served as a model to study the folding process and the importance of IH among the apolar residues in its polypeptide chain.

In a study carried out by Dyson et al. In 2006 where mutated sequences of apomyoglobin were used, it was shown that the initiation of apomyoglobin folding events depends primarily on the HIs between amino acids with apolar groups of the alpha-helices.

Thus, small changes introduced in the amino acid sequence mean important modifications in the tertiary structure, which gives rise to poorly formed and inactive proteins.

Detergents

Another clear example of HI is the mode of action of commercial detergents that we use for domestic purposes every day.

Detergents are amphipathic molecules (with a polar region and an apolar region). They can "emulsify" fats as they have the ability to form hydrogen bonds with water molecules and have hydrophobic interactions with lipids in fats.

When in contact with fats in an aqueous solution, the detergent molecules associate with each other in such a way that the apolar tails face each other, enclosing the lipid molecules, and the polar regions are exposed towards the surface of the micelle, which enter contact with water.

References

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