Chemistry Reference
In-Depth Information
17
Biologically Relevant Chemistry
of Nitroxides
Sara Goldstein
1
and Amram Samuni
2
1
Institute of Chemistry and the Accelerator Laboratory, The Hebrew University of Jerusalem, Jerusalem,
Israel
2
Department of Molecular Biology, The Hebrew University of Jerusalem - Hadassah Medical School,
Jerusalem, Israel
17.1
Introduction
The ever-increasing knowledge of the involvement of radicals in diverse pathological processes has
expanded the search for more efficient antioxidants that can diminish radical-induced damage. Accord-
ingly, the activity of a broad array of potentially useful antioxidants has been extensively studied. These
antioxidants include enzymes such as superoxide dismutase (SOD) and catalase, which remove superox-
ide (HO
2
•
/O
2
•
−
)
and H
2
O
2
, respectively; chelators that render transition metal ions redox inactive thus
pre-empting Fenton-like reactions; and low molecular weight antioxidants (LMWA) that react with toxic
radicals terminating radical chain reactions and restituting impaired cellular sites. A more restrictive class of
antioxidants is confined to natural or synthetic, hydrophilic or lipophilic LMWA alone, for example, ascor-
bate, urate, trolox, vitamin
E
,
-carotene, butylated hydroxytoluene, carnosine, polyphenols, flavonoids,
and thiols. However, the protective effect of administered SOD against oxidative stress is limited by its
short half-life in the circulation and its inability to cross cell membranes.
1,2
LMWA, which are diamag-
netic, operate primarily by reducing deleterious oxidants. They are progressively depleted from the tissue,
particularly under oxidative stress, and yield secondary radicals that might also induce biological damage.
Cyclic nitroxides (R
2
NO
•
) are cell-permeable stable radicals of diverse size, charge, and lipophilicity
stabilized by methyl groups at the
β
position in five-membered pyrrolidine, pyrroline, or oxazolidine and
six-membered piperidine ring structures. The structures of several nitroxides used in our studies are given
in Figure 17.1.
Cyclic nitroxides have been used for years as biophysical probes to monitor membrane dynamics,
3
cel-
lular pH,
4
redox state
in vivo
,
5
as potential contrast agents for magnetic resonance imaging (MRI),
6
and
catalysts for specific oxidation of alcohols and sugars.
7-9
The observation
10,11
that cyclic nitroxides catalyze
α
Search WWH ::
Custom Search