Res. Chem. Intermed., Vol. 29, No. 6, pp. 533–552 (2003)
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Allopurinol and its interactions with Cu
reactions and complex structure
and ARMIDA TORREGGIANI
Istituto I.S.O.F. (C.N.R.), Via P. Gobetti 101, 40129 Bologna, Italy
Received 3 March 2003; accepted 31 March 2003
Abstract—Allopurinol (ALP), an inhibitor of the xanthine oxidase enzime, is reported to provide
protection against free-radical mediated damage by various mechanisms, including free-radical
scavenging and metal chelation (i.e. Cu(II)). To obtain a wider insight into the molecular aspects of
the bene cial action of ALP, free ALP and the Cu(II)– ALP system were investigated by radiation
chemical and spectroscopic studies. Pulse radiolysis experiments show that ALP is a good
at pH 6.0 and 11.0, respectively), leading to
adducts and transient semi-oxidized species, such as phenoxyl radicals. The latter are also formed
by the reaction of ALP with some speci c one-electron oxidizing radicals (i.e. N
semi-oxidized species are stabilized by their resonance properties and scarcely react with oxygen.
In addition, the chelation of Cu(II) by ALP does not signi cantly affect the reactivity of the drug
). Raman and the IR spectra support the good chelating ability of ALP,
indicating the formation of two Cu(II)– ALP complexes with a slightly different structure. Depending
on the metal/ligand ratio, pyrimidine nitrogens may take part to the Cu(II) co-ordination in addition to
the N pyrazolic atoms and the C O groups of some ALP molecules. These results suggest that ALP
may inhibit oxidative damage both through the direct radical scavenging and the copper-chelation
mechanism. In fact, both the conversion of a harmful radical, such as
OH, into a less reactive transient
species, and the capture of copper ions, which play a relevant role in metal-catalysed generation of
reactive oxygen species, will prove bene cial for the cell protection.
: Allopurinol; radicals; copper/ allopurinol complexes; pulse radiolysis; Raman spec-
troscopy; IR spectroscopy.
Reactive oxygen-derived species play a part in mediating myocardial reperfusion
injury after ischemia in animal tissues ; this has led to intensive investigation
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