The chemistry of life is largely about organic chemistry, and organic chemistry boils down to recognizing the physics behind covalent bonds. In particular, when covalently bonded atomic nuclei have different numbers of protons, there are many physical consequences. Consider two similar molecules: ethanol and ethane. Their compositions differ in only one atom; oxygen. However, Oxygen practically always generates uneven electrical properties in covalent bonds. One consequence of this is intermolecular electrical attraction. This makes ethanol molecules boil at a much higher temperature than ethane because ethanol is literally electrically attracted to itself. The electrical imbalance of the carbon-oxygen and oxygen-hydrogen bonds generates permanent partial charges localized on the individual atoms, commonly referred to as dipole moments. Ethanol, despite being one type of molecule, has energetically favorable interactions with itself when it lines up its partial positive charge on its hydrogen with its partial negative charge on its oxygen. The concepts of intermolecular forces are essential to life chemistry. The simple concept of electrical attraction between opposite charges goes a very long way to describe biological processes. The massive carbon networks that biological systems have function on ultra-sensitive scales due to electrical properties. A protein such as a transcription factor can scale billions of DNA molecules through its complementary electrical charge to DNA. The subtle electrical field differences between the 4 DNA base pairs allow site specific DNA binding proteins to “read” the sequences also. These microscopic electrical phenomena are analogous to how humans read consistently applied letters in an alphabet on the large scale. A truly fascinating process. Let’s consider carbon a bit more thoroughly.
Many molecular processes are simplified by taking a step back and gazing upon the general trends in organic molecules. The skeleton of every sophisticated organic molecule is comprised of an atom with an atomic number of 6, AKA carbon. This parameter, atomic number, bears a special relation to the valence shell of carbon as well as the majority of biologically relevant atoms; it is halfway full and halfway empty simultaneously. This important electronic property of carbon endows it with life generating potential. Carbon is similar to a metal, adept at bearing a partially positive character when covalently bonded to nitrogen or oxygen, which is fundamental to protein chemistry. Paradoxically carbon can also be the electronic hub when bonded to only hydrogen or less electronegative atoms. Carbon is clearly a more sophisticated “metal” than its heavier cousins bearing d-orbital electrons. In biological systems, this sophistication is manifest as electronic gradients when transition metals are chelated in enzymes. Carbon can geometrically facilitate oxygen or nitrogen to lend their lone pair electrons to stabilize a metal in a protein. Typically either a carboxylic acid group or a nitrogen atom “lean in” to the positive electronic environment of a metal to enable the metal to perform biologically necessary reactions. The phenomenon of metal chelation demonstrates the sophisticated electronics which preserve life. In man-made metal chelators such as ethylenediaminetetraacetic acid, or EDTA, carbon forms the backbone again and contributes to EDTA’s capacity to maintain a -6 charge overall. EDTA is useful; however it has far fewer potential roles than a protein.
In order to capitalize on the seemingly endless energy from the sun, organisms had to find a way to channel light energy into other forms. The covalent bonds in sugar are one example of how light energy can be transferred to other forms. A vital step in this process is conjugated systems of organic molecules. It is here that the magic of carbon takes center stage. By adjusting the length of a carbon chain and the type of double bonds, light will be absorbed by a molecule at slightly different frequency. Carbon facilitates energy transfer to occur at incredibly precise light wavelengths. The special relation between carbon, energy, and light provides the vivid detail of life.
One cannot discuss life and chemistry without recognizing how pivotal nitrogen is in the grand scheme. First, the limitations of nitrogen describe why it does not have the leading role that carbon does. Since it has 5 valence electrons, 3 short of a full valence shell, it is electronically “tilted” in a different way than carbon. Nitrogen’s properties are more suited to the wild card of carbon networks since it can shift between 3 covalent bonds and four under different conditions. When nitrogen is bonded to four molecules, there is a shift in the geometry of a molecule as well as its charge. This generates chemical flexibility for life. It also generates issues in DNA when side reactions occur. If DNA’s geometry changes, mutations are more likely. The nitrogen in DNA is liable to react with things as common as the sun’s ultraviolet radiation and water. Nitrogen’s electric properties paradoxically make repairing DNA more easy. DNA repair proteins can tell very quickly when there is something wrong which is clear from the 99.9 percent repair rate of all mutations in many organisms.
Many vitamins shift between forms where nitrogen is charged or uncharged. Carbon lacks such a flexibility, showing how many atoms must cooperate to make life possible. Metaphorically, this is analogous to how many individual efforts make the propagation of human life possible. Nitrogen also has several roles in the energy currency of cells. Vitamins, or cofactors, are molecules like NADH (nicotinamide adenine dinucleotide) which are central to accomplishing many biological processes. It is analogous to the usefulness of a currency which can buy practically anything in a free market. In the cell, there are several currencies based on the physical properties of the “money”, with some being associated to membranes due to their molecular features. When it comes to life, nitrogen and carbon combine forces literally and figuratively. Life has a few other pivotal atoms which have their own roles in the propagation of life.
Sulfur, a heavier cousin of oxygen, is another atom vital to life. In biochemistry, sulfur is a highly effective nucleophile, especially in physiological environments. Nucleophiles are extremely important in any chemical reaction, so sulfur has a very special role. Relative to oxygen, its electron density is more widely distributed. One analogy to this is that of the friendly neighbor. Sulfur has a much greater propensity to share electrons than oxygen. In this analogy, oxygen is the cold, closed-off neighbor. Oxygen’s electron distribution is too dense to be kinetically effective in as many biochemical reactions. Since sulfur’s electron distribution can permeate a greater volume, bonds can be formed more readily than oxygen. Unfortunately this is a double edged sword. A large issue in oxidative damage to proteins is due to sulfur’s reactivity with oxygen. If a cysteine amino acid residue becomes oxidized to a sulfoxide or sulfone, many issues can arise with respect to protein function. In another chemical metaphor, sulfur is occasionally too friendly to various chemical species, resulting in more frequent oxidative damage to the body.
DNA has a special place in the annals of biochemistry. It constitutes the essence of human life, the biochemical alphabet soup repeating an endless improvement in syntax to each environment. Extended DNA molecules, or polymers, have delocalized negative charges on oxygens bonded to the phosphate group. This chemical motif provides proteins with a geometric road map of how to generate electrically attractive interactions with DNA. Consequently there are many families of DNA binding proteins. RNA has just as many proteins which interact with it. RNA differs in that it is more hydrophilic due to an extra hydroxyl group within its sugar moiety facilitating even more specific electrical interactions. Nature, through its divine engineering, made RNA the vector of every protein due to its greater capacity to move through water. The arrangement of DNA and RNA within the central dogma of biology provides many mechanisms for regulating biochemical activity in an organism.