Biochemistry - The Chemical Reactions of Living Cells, Volume 1 - D. Metzler 1980

The molecules we are made of
Principles of small molecule architecture
Hydrogen bonds and hydrophobic interactions

Although the integrity of a molecule is maintained by covalent bonds, many of the most vital properties of biological compounds are determined by significantly weaker bonds. Among these non-covalent bonds, hydrogen and Hydrophobic bonds are of primary importance. Hydrogen Bonds arise from electrostatic attraction caused by the uneven distribution of electrons between atoms participating in a covalent bond: for instance, in a Water molecule, the electrons forming the H—O bond are slightly shifted toward the oxygen atom. As a result, a small uncompensated positive charge is created on the hydrogen atom, and a small negative charge on the oxygen atom. The presence of such polarization is sometimes indicated by arrows replacing the representation of chemical bonds; designations like δ⁺ and δ^- are also used. Molecules with strongly polarized bonds are called polar, as are functional groups containing such bonds. They are contrasted with non-polar groups, such as the —СН₃-group, where the bonding electrons are distributed almost evenly between the carbon and hydrogen atoms.

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A Hydrogen bond is formed when the positively charged end of one dipole (one of the polarized bonds) is attracted to the negatively charged end of another dipole. The ability to form hydrogen bonds is highly pronounced in water molecules; furthermore, each oxygen atom can form hydrogen bonds with two other water molecules. Hydrogen bonds exhibit a sharply pronounced directional character: the bond is strongest when all three atoms lie on a straight line. The enthalpy of formation of a hydrogen bond along a straight line, ∆H°, can reach —20 kJ∙mol^-1 (—5 kcal∙mol^-1).

Hydrogen bonds are longer than covalent bonds, but noticeably shorter (by ~0.06—0.08 nm) than the distances corresponding to interatomic contacts determined by Structure/103.html">Van der Waals radii. It should be borne in mind that hydrogen bonds are always formed between pairs of groups, one of which faces the other with the negative end of the dipole, while the other serves as a proton donor. The group acting as a proton acceptor can also be viewed as a lone-pair electron donor. When discussing organic reaction mechanisms, it is customary to use arrows to indicate the direction of electron displacement. In this book, we will also occasionally indicate the direction of hydrogen bonds using arrows pointing from electron Donors to hydrogen atoms (as done above when discussing The formation of hydrogen bonds between water molecules).

Fats, Hydrocarbons, and other substances whose molecules consist primarily of non-polar groups are poorly soluble in water and readily soluble in non-polar Solvents. In an aqueous environment, non-polar groups tend to associate—a phenomenon frequently referred to as hydrophobic interaction. Conversely, sugars and Other Compounds containing numerous polar groups are, by contrast, highly soluble in water and do not associate.

The solubility of sugar in water is explained by the ability of its numerous hydroxyl groups to form hydrogen bonds with water molecules. The Nature of hydrophobic binding, which will be discussed in Chapter 4 (Section B.4), is somewhat more difficult to understand, but it is primarily driven by the strong mutual attraction of water molecules involved in a dense network of hydrogen bonds [7].

Many molecules containing ring structures (such as Purines or Pyrimidines) are relatively poorly soluble in both water and organic solvents. The molecules of these compounds, containing both polar and non-polar regions, show no preference for either solvent and pack tightly within the solid crystal structure.