Ternary copper complexes and manganese (III) tetrakis(4-benzoic acid) porphyrin catalyze peroxynitrite-dependent nitration of aromatics.
Peroxynitrite is a powerful oxidant formed in biological systems from the reaction of nitrogen monoxide and superoxide and is capable of nitrating phenols at neutral pH and ambient temperature. This peroxynitrite-mediated nitration is catalyzed by a number of Lewis acids, including CO2 and transition-metal ion complexes. Here we studied the effect of ternary copper-(II) complexes constituted by a 1,10-phenanthroline and an amino acid as ligands. All the complexes studied accelerate both the decomposition of peroxynitrite and its nitration of 4-hydroxyphenylacetic acid at pH > 7. The rate of these reactions depends on the copper complex concentration in a hyperbolic plus linear manner. The yield of nitrated products increases up to 2.6-fold with respect to proton-catalyzed nitration and has a dependency on the concentration of copper complexes which follows the same function as observed for the rate constants. The manganese porphyrin complex, Mn(III)tetrakis(4-benzoic acid)porphyrin [Mn(tbap)], also promoted peroxynitrite-mediated nitration with an even higher yield (4-fold increase) than the ternary copper complexes. At pH = 7.5 +/- 0.2 the catalytic behavior of the copper complexes can be linearly correlated with the pKa of the phenanthroline present as a ligand, implying that a peroxynitrite anion is coordinated to the copper ion prior to the nitration reaction. These observations may prove valuable to understand the biological effects of these transition-metal complexes (i.e., copper and manganese) that can mimic superoxide dismutase activity and, in the case of the ternary copper complexes, show antineoplastic activity.
Ferrer-Sueta
G
G
Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Uruguay.
Ruiz-Ramírez
L
L
Radi
R
R
D002614:Chelating Agents / Q000494:pharmacology*; D003300:Copper / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008665:Metalloporphyrins / Q000494:pharmacology*; D009566:Nitrates / Q000378:metabolism*; D016877:Oxidants / Q000378:metabolism*; D010618:Phenanthrolines / Q000494:pharmacology*; D010648:Phenylacetates / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship
D002614:Chelating Agents; D016166:Free Radical Scavengers; D008665:Metalloporphyrins; D009566:Nitrates; D016877:Oxidants; D010618:Phenanthrolines; D010648:Phenylacetates; C097284:manganese(III)-tetrakis(4-benzoic acid)porphyrin; C039642:peroxynitric acid; C008070:4-hydroxyphenylacetic acid; D003300:Copper; C025205:1,10-phenanthroline