7.1. Nucleobases
The fundamental information storage components of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) are the nucleobases. A nucleobase is a nitrogen-containing heterocyclic compound that can be attached to a saccharide-phosphate to form either structure. The name for this class of compounds sometimes leads to confusion. The “base” portion of the name refers to the general basicity of nitrogen-containing heterocycles but is not (normally) relevant; nucleobases may or may not be good bases for acid-base chemistry.
This chapter focuses on the uses of nucleobases in genetic material (DNA/RNA). However, not all applications of nucleobases/nucleotides are in DNA/RNA. For example, in the nicotinamide adenine dinucleotide (NAD+) coenzyme nicotinamide is a nucleobase (Figure 7.1). While not directly relevant to this chapter it is important to remember that other compounds are used as nucleobases and that they can perform other functions than for information storage in genetic code.
Figure 7.1 – Structure of Nicotinamide Adenine Dinucleotide Highlighting Nicotinamide as a Nucleobase.
7.1.1. The Five Common Nucleobases
In principle any nitrogen-containing heterocyclic compound could act as a nucleobase. In practice five heteroaromatic rings are very common (Figure 7.2). These ring structures are so common that they each have their own trivial name and a one-letter shorthand notation. For the five common bases the shorthand notation is simply the first letter of the trivial name. Technically, the common nucleobases also have a three-letter shorthand notation. However, these are rarely used and are typically avoided by the majority of (bio)chemists.
Figure 7.2 – Structure, Trivial Name, and One-Letter Code for The Five Common Nucleobases.
Most nucleobases are broadly divided into two sets depending on whether the structure is a modification of a simple purine or pyrimidine heteroaromatic ring. As a result, adenine and guanine are referred to as “purine nucleobases” (sometimes simply “purine bases”) and cytosine, thymine, and uracil are referred to as “pyrimidine nucleobases” (sometimes simply “pyrimidine bases”).
Other compounds can be used as nucleobases. Often these are small modifications to the main five structures. For example, some viruses use 2-aminoadenine instead of adenine in parts of their genetic code (Figure 7.3). Many of these also have their one-letter shorthand notations. However, these are often not simply abbreviations of their names and are not intuitive. This text will not use these one-letter codes but they may be encountered in other sources.
Figure 7.3 – Structure and One-Letter Code for 2-Aminoadenine with Comparison to Adenine and Guanine.
7.1.2. Properties of the Common Nucleobases
The five common nucleobases have several properties in common. These properties contribute to their widespread use.
Each of the common nucleobases is completely planar (Figure 7.4). All of the atoms in each of the heterocyclic rings are sp2 hybridized and have trigonal planar geometry. This is also true of the amine/carbonyl groups attached to the rings; the entire nucleobase is flat.
Figure 7.4 – Structures of the Five Common Nucleobases Showing Planarity.
This can be seen by drawing resonance structures and then assigning hybridization (Figure 7.5). The specific resonance forms shown are NOT highly contributing, they are shown because they combine all necessary components to show that all of the atoms are sp2 hybridized (trigonal planar).
Figure 7.5 – Resonance Structures of the Five Common Nucleobases Highlighting sp2 (Trigonal Planar) Geometry.
Each of the common nucleobases is aromatic (Figure 7.6). They each have a cyclic structure, have non-orthogonal p orbitals on all atoms in the ring, are planar, and obey Hückel’s Rule (the number of π electrons in the ring system must be a solution to [4n+2]). In the standard structure this can be challenging to see. However, a valid resonance form exists for each in which the aromaticity is more obvious. This also makes their relationship to purine/pyrimidine more apparent.
Figure 7.6 – Resonance Structures of the Five Common Nucleobases Highlighting Aromaticity.
Being aromatic leads to several of the important characteristics of DNA/RNA, including adding to its stability and leading to the characteristic double helix structure of DNA (see Section 7.4.3).
Each of the common nucleobases has hydrogen bonding donor/acceptor groups (Figure 7.7). This can be seen in the standard resonance forms but is simpler to interpret in their “aromatic” resonance forms. One of the NH groups will be modified to become part of the larger structure (see Section 7.2). Additionally, the lone pair from that nitrogen in each is occupied in resonance/aromaticity and is not available for hydrogen bonding. The remaining oxygens, nitrogens, and NH’s can act as hydrogen bond donors/acceptors.
Figure 7.7 – Positions of the Five Common Nucleobases as Hydrogen Bond Donors/Acceptors in DNA/RNA.
Technically the amine groups may act as either donors or acceptors. In practice these groups act as hydrogen bond donors in genetic material. In the purine nucleobases (adenine and quinine) there are two nitrogen atoms with lone pairs in the ring which can act as hydrogen bond acceptors but do not do so in DNA/RNA. The multiple available positions for hydrogen bonding leads to several of the important characteristics of DNA/RNA, including leading to the characteristic double helix structure of DNA (see Sections 7.3.2 and 7.4.3).
