The Mitochondrial Free Radical Theory of Aging - Supernova: Pliki

CHAPTER 3
An Introduction to Free Radicals
3.1. Another Terminological Apology: “Pairing” of Electrons
It is most unfortunate that the term “free radical” has become so firmly entrenched in the
vocabulary of gerontology, especially in the popular press. The problem is that the meaning
which is generally attached to it has several major differences from its strict chemical
definition.
Free radicals are a class of molecule with a very simple definition. The nature of atomic
structure and of the covalent chemical bond, the features that give an atom its valency, are
underpinned by the rule that electrons occupy orbitals of atoms, such that an orbital can
contain zero, one or two electrons, and that electrons carry less energy when they are one of a
pair in an orbital than when they are unpaired. A molecule is a free radical if and only if it
possesses any unpaired electrons. That’s all. Some are composed of only two atoms; some are
huge, being made by removing one electron from, for example, a protein or a chromosome.
If one were to try to infer what a free radical is solely from reading the gerontological
literature, however, one would form the impression that a free radical is a small, highly
reactive, highly toxic, oxygen-centred molecule which can be rendered less toxic by the
addition or removal of one electron. This is a clear case of a little knowledge being a dangerous
thing; it is near enough to the real definition to seem trustworthy, but it can easily cause
misunderstanding of important details.
So, what are the specific differences between these two definitions? Superficially,
“unpaired” might be thought to connote that free radicals have an odd number of electrons,
whereas all other molecules have an even number. Unfortunately, “pairedness” is defined in
terms of the physical interactions of a molecule’s electrons, and those interactions are much
more complicated than that. For a start, the vagaries of atomic structure in fact allow a
molecule to have two unpaired electrons at once. Such molecules are called diradicals. In
practice, however, the only diradical which will concern us is molecular oxygen (O2), and its
electrons are arranged in such a way that, for purposes of reactivity, its unpaired electrons
behave rather as if they are paired after all.*
Another class of chemical which sometimes breaks the correlation between pairedness
and evenness is atoms. Atoms that contain an odd number of electrons are not called free
radicals, and indeed those that exist in cells do not quite behave in the same way as bona fide
free radicals do. Some of the most biologically important examples are atoms of transition
metals, which can carry varying numbers of electrons; iron and copper, in particular, will
feature extensively in this book. But curiously, these atoms are both more “free-radical-like”
when carrying an even number of electrons!
* The electrons of O2 can be arranged differently, so that it does behave like a radical: it is then termed singlet
oxygen. This variant of O2 is written 1 O2 and plays a role in light-induced skin damage; 1a see also Table 3.3
and Section 11.2.3.
The Mitochondrial Free Radical Theory of Aging, by Aubrey D.N.J. de Grey.
©1999 R.G. Landes Company.