Free radical scavangers – antioxidents
A molecule with one or more unpaired electron in its outer shell is called a free radical. Free radicals are formed
from molecules via the breakage of a chemical bond such that each fragment keeps one electron, by cleavage of a
radical to give another radical and, also via redox reactions.
Oxygen is an element indispensable for life. When cells use oxygen to generate energy, free radicals are created
as a consequence of ATP (adenosine triphosphate) production by the mitochondria. These by-products are
generally reactive oxygen species (ROS) as well as reactive nitrogen species (RNS) that result from the cellular
redox process. ROS and RNS are the terms collectively describing free radicals and other non-radical reactive
derivatives also called oxidants. Radicals are less stable than non-radical species, although their reactivity is
generally stronger.
Free radicals include hydroxyl (OH•), superoxide (O2 •ˉ), nitric oxide (NO•), nitrogen dioxide (NO2 •), peroxyl
(ROO•) and lipid peroxyl (LOO•). Also, hydrogen peroxide (H2O2 ), ozone (O3 ), singlet oxygen (1O2 ),
hypochlorous acid (HOCl), nitrous acid (HNO2 ), peroxynitrite (ONOOˉ), dinitrogen trioxide (N2O3 ), lipid
peroxide (LOOH), are not free radicals and generally called oxidants, but can easily lead to free radical reactions
in living organisms.
Characteristics of Free Radicals:
Like carbocations, free radicals are sp2 hybridized and planar (or nearly planar). Unlike carbocations, however,
the p orbital perpendicular to the plane of the bonds of the radical is not empty; it contains the odd electron. Both
radicals and carbocations are electron deficient because they lack an octet around the carbon atom. Like
carbocations, radicals are stabilized by the electron donating effect of alkyl groups, making more highly
substituted radicals more stable. Like carbocations, radicals can be stabilized by resonance. Overlap with the p
orbitals of a pi bond allows the odd electron to be delocalized over two carbon atoms. Resonance delocalization
is particularly effective in stabilizing a radical.
Stability Order of Free Radicals:
Free radicals are stabilized by:
Resonance:
The benzyl C6H5CH2⋅ and allyl CH2=CH−CH2⋅ radicals are highly stable due to the delocalization of the
unpaired electron through resonance. The benzylic radical has more resonance structures than the allylic radical,
making it slightly more stable in most general comparisons.
Hyperconjugation and Inductive effect:
For alkyl radicals (3°, 2°, 1°, and methyl), stability increases with the number of alkyl groups attached to the
carbon bearing the unpaired electron. This is due to the electron-donating inductive effect (+I) and
hyperconjugation, which disperse the electron density and stabilize the radical.
A molecule with one or more unpaired electron in its outer shell is called a free radical. Free radicals are formed
from molecules via the breakage of a chemical bond such that each fragment keeps one electron, by cleavage of a
radical to give another radical and, also via redox reactions.
Oxygen is an element indispensable for life. When cells use oxygen to generate energy, free radicals are created
as a consequence of ATP (adenosine triphosphate) production by the mitochondria. These by-products are
generally reactive oxygen species (ROS) as well as reactive nitrogen species (RNS) that result from the cellular
redox process. ROS and RNS are the terms collectively describing free radicals and other non-radical reactive
derivatives also called oxidants. Radicals are less stable than non-radical species, although their reactivity is
generally stronger.
Free radicals include hydroxyl (OH•), superoxide (O2 •ˉ), nitric oxide (NO•), nitrogen dioxide (NO2 •), peroxyl
(ROO•) and lipid peroxyl (LOO•). Also, hydrogen peroxide (H2O2 ), ozone (O3 ), singlet oxygen (1O2 ),
hypochlorous acid (HOCl), nitrous acid (HNO2 ), peroxynitrite (ONOOˉ), dinitrogen trioxide (N2O3 ), lipid
peroxide (LOOH), are not free radicals and generally called oxidants, but can easily lead to free radical reactions
in living organisms.
Characteristics of Free Radicals:
Like carbocations, free radicals are sp2 hybridized and planar (or nearly planar). Unlike carbocations, however,
the p orbital perpendicular to the plane of the bonds of the radical is not empty; it contains the odd electron. Both
radicals and carbocations are electron deficient because they lack an octet around the carbon atom. Like
carbocations, radicals are stabilized by the electron donating effect of alkyl groups, making more highly
substituted radicals more stable. Like carbocations, radicals can be stabilized by resonance. Overlap with the p
orbitals of a pi bond allows the odd electron to be delocalized over two carbon atoms. Resonance delocalization
is particularly effective in stabilizing a radical.
Stability Order of Free Radicals:
Free radicals are stabilized by:
Resonance:
The benzyl C6H5CH2⋅ and allyl CH2=CH−CH2⋅ radicals are highly stable due to the delocalization of the
unpaired electron through resonance. The benzylic radical has more resonance structures than the allylic radical,
making it slightly more stable in most general comparisons.
Hyperconjugation and Inductive effect:
For alkyl radicals (3°, 2°, 1°, and methyl), stability increases with the number of alkyl groups attached to the
carbon bearing the unpaired electron. This is due to the electron-donating inductive effect (+I) and
hyperconjugation, which disperse the electron density and stabilize the radical.
