More On Radicals

Historically, radicals had a bad reputation in organic chemistry. Radicals were often assumed by chemists to be so reactive (they have an unpaired electron that presumably wants to get paired by getting involved in bonding) that their reactions could not be controlled. Actually, many radicals react more slowly and selectively than many ionic intermediates, and many synthetically useful radical reactions have been introduced are now in regular use. The key point is just because a radical has an unpaired electron, it doesn't need to get into a bond any more than many other kinds of non-bonding electrons.

I think that this is now understood by most chemists now, however radicals maintain their bad reputation in the public domain. Innumerable publications and web sites cite the fact that radicals are "toxic" because they are so reactive etc. Radicals are at the center of one of these silly nutrition/aging/health fads that plague the popular media. Obviously, noone wants radicals wandering around at random in their system, but to tar radicals as "toxic" is patently ludicrous.

In fact, radicals are involved in many metabolic processes. An obvious example is the conversion of the ribonucleotides required for RNA synthesis to deoxyribonucleotides that are used in DNA synthesis. This is accomplised using a ribonucleotide reductase enzyme, and a schematic mechanism is shown below.

The ribonucleotide is shown in red, and the deoxyribonucleotide is in blue. The reductase enzyme is shown schematically in magenta. In step (1), a hydrogen atom is abstracted from the sugar to generate the radical. A hydroxy group is then protonated (step (2)), and leaves as water (step (3)) to generate a radical cation. (We will see steps (2) and (3) again many times later in our course!) The radical cation then picks up a hydride from the enzyme (step 4)) to generate a second radical, followed by a hydrogen atom in the final step (5).

The body does seem to have methods of dealing with radicals that are generated inadvertantly, however (in addition to many other species). These are often generically called radical inhibitors, or anti-oxidants, although that is not a good name for reasons I don't want to get into here! An example of an antioxidant (not a natural one as far as I am aware) is hydroquinone, shown below in red. It is capable of "consuming" 2 radicals as shown. The key intermediate is a resonance stabilized oxygen centered radical (magenta) and the product is quinone (blue).

Two natural radical inhibitors are Vitamin C (also known as ascorbic acid, red below) and vitamin E (also known as a-tocopherol, blue below). One works in the mainly aqueous environments of cells and plasma, the other works in mainly nonaqueous parts of cells.

Which one works in which environment, and why?