Free radicals

The electrons in an atom revolve in orbitals around
the nucleus. Each orbital can hold a maximum of two
electrons paired with antiparallel spin, resulting in no
net spin. A free radical can be defi ned as an atom or
molecule capable of independent existence that contains
one or more unpaired electron(s). The unpaired
electron is found alone in the outer orbital and is
denoted by a superscript dot next to the element. The
simplest free radical is an atom of hydrogen (H•), with
one proton and a single electron. Reduction of oxygen
by the transfer to it of a single electron will produce
the superoxide anion radical (‘superoxide’), usually
represented by O2
•–. The oxygen molecule itself is a
free radical because it has two unpaired electrons in
different orbitals. Owing to their unstable electronic
confi guration, free radicals are much more reactive
than non-radicals. They readily extract electrons
from other molecules with which they collide, and
these molecules in turn become free radicals. Thus a
chain reaction is propagated.
Free radicals are generally produced by electron
transfer reactions catalysed either enzymatically or
non-enzymatically through the redox chemistry of
transition metal ions. There are many ways of generating
free radicals. Examples include phagocytosis
during infection; metabolic processing of foreign
compounds (e.g. constituents of tobacco smoke,
drugs, pesticides, solvents and pollutants); ultraviolet
irradiation of the skin; and ionizing radiation. A
major source of superoxide is electron ‘leakage’ from
the mitochondrial electron transport chain to molecular
oxygen. Another source of superoxide is the
metal-catalysed autoxidation of certain compounds
including catecholamines, ascorbic acid, thiols (e.g.
glutathione, cysteine), tetrahydrofolate and reduced
fl avins. Physical exercise leads to a greater production
of free radicals relative to the greater oxygen consumption
(Giuliani & Cestaro, 1997).
Free radicals range from very oxidizing to very reducing
and their reduction potentials can be used to
predict a hierarchy for free radical reactions (Buettner,
1993). The most oxidizing free radical is the hydroxyl
radical (•OH) which, with a half-life of only 1 nanosecond
at 37°C, is so reactive that there is no time for
any molecule or radical to remove it before damage is
done. Damage to DNA and proteins is therefore unavoidable
and must be dealt with by repair enzymes.