The Hydrophobic Effect Causes Nonpolar Molecules to Adhere to One Another

Because nonpolar molecules do not contain charged groups, do not possess a dipole moment, and do not become hydrated, they are insoluble, or almost insoluble, in water; that is, they are hydrophobic. The covalent bonds between two carbon atoms and between carbon and hydrogen atoms are the most common nonpolar bonds in biological systems. Hydrocarbons—molecules made up only of carbon and hydrogen—are virtually insoluble in water. Large triacylglycerols (also known as triglycerides), which make up animal fats and vegetable oils, also essentially are insoluble in water. As we will see later, the major part of these molecules consists of long hydrocarbon chains. After being shaken in water, triacylglycerols form a separate phase. A familiar example is the separation of oil from the water-based vinegar in an oil-and-vinegar salad dressing.

Nonpolar molecules or nonpolar parts of molecules tend to aggregate in water owing to a phenomenon called the hydrophobic effect. Because water molecules cannot form hydrogen bonds with nonpolar substances, they tend to form “cages” of relatively rigid hydrogen-bonded pentagons and hexagons around nonpolar molecules (Figure 2-11, left). This state is energetically unfavorable because it decreases the entropy, or randomness, of the population of water molecules. (The role of entropy in chemical systems is discussed in Section 2.4.) If nonpolar molecules in an aqueous environment aggregate with their hydrophobic surfaces facing each other, the net hydrophobic surface area exposed to water is reduced (Figure 2-11, right). As a consequence, less water is needed to form the cages surrounding the nonpolar molecules, entropy increases relative to the unaggregated state, and an energetically more favorable state is reached. In a sense, then, water squeezes the nonpolar molecules into aggregates. Rather than constituting an attractive force, as in hydrogen bonds, the hydrophobic effect results from an avoidance of an unstable state—that is, extensive water cages around individual nonpolar molecules.

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FIGURE 2-11 Schematic depiction of the hydrophobic effect. Cages of water molecules that form around nonpolar molecules in solution are more ordered than water molecules in the surrounding bulk liquid. Aggregation of nonpolar molecules reduces the number of water molecules involved in forming highly ordered cages, resulting in a higher-entropy, more energetically favorable state (right) compared with the unaggregated state (left).

Nonpolar molecules can also associate, albeit weakly, through van der Waals interactions. The net result of the hydrophobic effect and van der Waals interactions is a very powerful tendency for hydrophobic molecules to interact with one another, not with water. Simply put, like dissolves like. Polar molecules dissolve in polar solvents such as water; nonpolar molecules dissolve in nonpolar solvents such as hexane.

One well-known hydrophobic molecule is cholesterol (see the structure in Section 2.2). Cholesterol, triglycerides, and other poorly water-soluble molecules are called lipids. Unlike hydrophilic molecules such as glucose or amino acids, lipids cannot readily dissolve in the blood, the aqueous circulatory system that transports molecules and cells throughout the body. Instead, lipids such as cholesterol must be packaged into special hydrophilic carriers, called lipoproteins, that can themselves dissolve in the blood and be transported throughout the body. There can be hundreds to thousands of lipid molecules packed into the center, or core, of each lipoprotein. The hydrophobic core is surrounded by amphipathic molecules that have hydrophilic parts that interact with water and hydrophobic parts that interact with one another and the core. The packaging of lipids into lipoproteins (discussed in Chapter 14) permits their efficient transport in blood and is reminiscent of the containerization of cargo for efficient long-distance transport via cargo ships, trains, and trucks.

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High-density lipoprotein (HDL) and low-density lipoprotein (LDL) are two such lipoprotein carriers that are associated with either reduced or increased heart disease, respectively, and are therefore often referred to as “good” and “bad” cholesterol. Actually, the cholesterol molecules and their derivatives that are carried by both HDL and LDL are essentially identical and in themselves are neither “good” nor “bad.” However, HDL and LDL have different effects on cells, and as a consequence, LDL contributes to and HDL appears to protect from clogging of the arteries (known as atherosclerosis) and consequent heart disease and stroke. Thus LDL is known as “bad” cholesterol.