Biology Reference
In-Depth Information
elsewhere (Foote, 1976; Kessel, 2000; Girotti,
2001; Schweitzer and Schmidt, 2003),
1
O
2
can react with biomolecules and cause dam-
age to their structures and functions. Each
main group of bio-structures, i.e. membranes,
proteins and nucleic acids, shows distinct
patterns of molecular damage and decrease
of bio-functionality. Membrane damage is
initiated by attack to the double bond of
unsaturated lipids through the formation of
lipid hydroperoxides (Girotti, 2001); pro-
teins have some susceptible amino acids that
are usually initially oxidized, i.e. tryptophan,
cysteine, methionine, tyrosine and histidine
as well as some redox prosthetic groups
(Foote, 1976). DNA is damaged particularly in
guanosine residues forming 8-oxoguanosine,
which facilitates the continuation of the oxi-
dation progress because 8-oxoguanosine is
much more susceptible to oxidation than
guanosine itself (Devasagayam
et al
., 1991).
In this chapter most emphasis is given to
membrane damage.
Lipid hydroperoxides (LOOH) are the
initial species generated when membranes
made of unsaturated lipids are attacked by
singlet oxygen (Fig. 6.11). The progression
of the peroxidation reactions depends on
the formation of peroxyl (LOO
•
) and alkoxyl
(LO
•
) radicals. Metals are able to catalyse
the conversion from LOOH to LOO
•
and
LO
•
. Also PSs that engage in type I reactions
or any PS in the presence of LOOH can also
catalyse the formation of LOO
•
and LO
•
(Gantchev
et al
., 2003). The progression of
peroxidation reactions can cause severe
damage to membrane properties and quickly
lead the cell to necrotic death. Indeed, the
efficiency of cell death caused by singlet
oxygen seems to be related to the efficiency
with which the PS interacts with mem-
branes (Pavani
et al
., 2009).
Diene
HOMO
Diene
LUMO
Dienophile
LUMO
Dienophile
HOMO
Fig. 6.8.
Frontier molecular orbital analysis of a
[4 + 2] cycloaddition reaction.
h
v
, O
2
(a)
MB, MeOH -20 to
-130°
mp +8.5°
Ph
Ph
Ph
OOH
1
O
2
OOH
1
O
2
(b)
Ph
Ph
Ph
Ph
Ph
Ph
Ph
h
v
, O
2
(c)
Self-sensitized
Ph
Ph
Ph
Ph
Fig. 6.9.
Cycloadditions using singlet oxygen as dienophile.
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