Tris(2,3,5,6)-tetrachloro-4-nitrophenyl)methyl Radical
SCHEME 1
phenoxyl radical. The other possible mechanism involves an
electron transfer from the polyphenol to the ROS. In general,
the ability of polyphenols to donate hydrogen atoms is closely
related to their capacity to transfer electrons.6 This electron-
transfer capacity may not be always beneficial since some
catechins with low oxidation potentials may end up being pro-
oxidant. In what is known as redox cycling, they are able to
transfer an electron to oxygen and generate the superoxide
radical, a very active radical which is enzymatically converted
into hydrogen peroxide.7,8 Moreover, the super oxide radical
appears to mediate apoptosis (programmed cell death).9 The key
structural features determining the chemical reactivity and
biological activity of catechins are the catechol or pyrogallol
moieties on ring B and the gallate (benzoylic pyrogallol) on
ring D (Scheme 1). Pyrogallol appears to be more reactive than
catechol,10 and the gallate moiety may mediate some key cancer
related biological events such as inhibition of the proteasome11
and of other enzymic domains.12
One of the most extensively used methods to evaluate the
antioxidation activity of polyphenols is the reduction of the
stable radical 2,2-diphenyl-1-picrylhydrazyl (DPPH).13 The
mechanism of the reduction depends on the nature of polyphenol
and the solvent. These reactions have been largely admitted to
occur by hydrogen atom abstraction, although recently some
authors have shown that in hydroxylic solvents they can proceed
from an electron transfer of the phenolate anion, in equilibrium
with its molecular counterpart, to the DPPH radical.14 Moreover,
an electron transfer from the neutral species in polyphenols with
very low oxidation potential values cannot be ruled out in some
cases.15
We have been engaged for some time in the synthesis and
evaluation of the antioxidant properties of new derivatives of
catechins, particularly flavanols conjugated with thiols.16 We
have measured both H-atom donation and electron-transfer
capacities in catechins and found that the electron-transfer
capacity may be directly related to the ability of these polyphe-
nols to induce cellular apoptosis.17 Because the DPPH test is
not capable of differentiating hydrogen donation from electron
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