Chemistry Reference
In-Depth Information
Termination
Reactive free radicals join together to form covalent bonds. This effectively
ends the chain reaction process and produces stable compounds.
Stage 3 Chain termination:
reactive free radicals are consumed but
not generated.
Drug-O-O
Drug
Drug-O-O-Drug
Drug
Drug
Drug-Drug
Figure 8.3
The mechanism of termination.
Stability of free radicals
It is useful to be able to look at the structure of a drug molecule and be able
to predict which sites, if any, in the molecule are susceptible to oxidative
deterioration. To do this we must have an understanding of the ease of
formation and the stability of free radical species.
The most common bond in a drug molecule to be broken during an
autoxidation process is a covalent bond between hydrogen and another
atom, usually carbon. It follows, therefore, that the more easily this bond
undergoes homolysis, the more susceptible the drug will be to autoxidation.
See Figure 8.4.
Drug
H
Drug
+
H
Figure 8.4
Autoxidation of carbon-hydrogen bonds.
The breaking of a bond in this way generates two radicals, each with
an unpaired electron. (Note the curved half-arrows in the reaction mechan-
ism. These signify the movement of
one
electron, as opposed to the full
arrow found in most reaction schemes, which implies the movement of
two
electrons.) Although almost all free radicals are unstable and react to gain
an extra electron to complete a full octet of electrons in their outer electron
shell, some radicals are
relatively
more stable than others, and hence will be
more likely to form and persist. In general, the more substituted a radical is
(with alkyl groups) the more stable it will be, and the more likely it will be
to take part in chemical reactions. A rank order can be drawn up that lists
the relative stabilities of free radicals; a highly substituted tertiary (3
)
radical is considerably more stable than a secondary (2
) or a primary (1
)
