Ferrer-Sueta G, Ruiz-Ramírez L, Radi R
Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Uruguay.
Chem Res Toxicol. 1997 Dec;10(12):1338-44. doi: 10.1021/tx970116h.
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.
过氧亚硝酸盐是生物系统中由一氧化氮和超氧化物反应生成的一种强氧化剂，能够在中性pH值和环境温度下使酚类硝化。这种过氧亚硝酸盐介导的硝化反应由多种路易斯酸催化，包括二氧化碳和过渡金属离子络合物。在此，我们研究了由1,10 - 菲咯啉和氨基酸作为配体构成的三元铜（II）络合物的作用。所研究的所有络合物在pH > 7时均能加速过氧亚硝酸盐的分解及其对4 - 羟基苯乙酸的硝化反应。这些反应的速率以双曲线加线性的方式取决于铜络合物的浓度。相对于质子催化的硝化反应，硝化产物的产率提高了2.6倍，并且对铜络合物浓度的依赖性与观察到的速率常数遵循相同的函数关系。锰卟啉络合物，即四（4 - 苯甲酸）卟啉锰（III）[Mn（tbap）]，也促进了过氧亚硝酸盐介导的硝化反应，其产率比三元铜络合物更高（增加了4倍）。在pH = 7.5±0.2时，铜络合物的催化行为与作为配体存在的菲咯啉的pKa呈线性相关，这意味着在硝化反应之前，过氧亚硝酸盐阴离子与铜离子配位。这些观察结果对于理解这些能够模拟超氧化物歧化酶活性的过渡金属络合物（即铜和锰）的生物学效应可能具有重要价值，并且对于三元铜络合物而言，还显示出抗肿瘤活性。
