Ferrer-Sueta G, Batinić-Haberle I, Spasojević I, Fridovich I, Radi R
Unidad Asociada Enzimología and Departamento de Fisicoquímica Biológica, Facultad de Ciencias, Universidad de la República, 11800 Montevideo, Uruguay.
Chem Res Toxicol. 1999 May;12(5):442-9. doi: 10.1021/tx980245d.
Three isomers of manganese(III) 5,10,15, 20-tetrakis(N-methylpyridyl)porphyrin (MnTMPyP) were evaluated for their reaction with peroxynitrite. The Mn(III) complexes reacted with peroxynitrite anion with rate constants of 1.85 x 10(7), 3.82 x 10(6), and 4.33 x 10(6) M(-1) s(-1) at 37 degrees C for MnTM-2-PyP, MnTM-3-PyP, and MnTM-4-PyP, respectively, to yield the corresponding oxo-Mn(IV) complexes. Throughout the pH range from 5 to 8.5, MnTM-2-PyP reacted 5-fold faster than the other two isomers. The oxo-Mn(IV) complexes could in turn be reduced by glutathione, ascorbate, urate, or oxidize tyrosine. The rate constants for the reduction of the oxo-Mn(IV) complexes ranged from >10(7) M(-1) s(-1) for ascorbate to 10(3)-10(4) M(-1) s(-1) for tyrosine and glutathione. Cyclic voltammetry experiments show that there is no significant difference in the E1/2 of the Mn(IV)/Mn(III) couple; thus, the differential reactivity of the three isomeric complexes is interpreted in terms of electrostatic and steric effects. Micromolar concentrations of MnTM-2-PyP compete well with millimolar CO2 at reacting with ONOO-, and it can even scavenge a fraction of the ONOOCO2- that is formed. By being rapidly oxidized by ONOO- and ONOOCO2- and reduced by antioxidants such as ascorbate, urate, and glutathione, these manganese porphyrins, and especially MnTM-2-PyP, can redirect the oxidative potential of peroxynitrite toward natural antioxidants, thus protecting more critical targets such as proteins and nucleic acids.
对锰（III）5,10,15,20 - 四（N - 甲基吡啶基）卟啉（MnTMPyP）的三种异构体与过氧亚硝酸盐的反应进行了评估。在37℃下，Mn（III）配合物与过氧亚硝酸盐阴离子反应，对于MnTM - 2 - PyP、MnTM - 3 - PyP和MnTM - 4 - PyP，反应速率常数分别为1.85×10⁷、3.82×10⁶和4.33×10⁶ M⁻¹ s⁻¹，生成相应的氧代 - Mn（IV）配合物。在pH值从5到8.5的整个范围内，MnTM - 2 - PyP的反应速度比其他两种异构体快5倍。氧代 - Mn（IV）配合物依次可被谷胱甘肽、抗坏血酸盐、尿酸盐还原，或氧化酪氨酸。氧代 - Mn（IV）配合物还原反应的速率常数范围从抗坏血酸盐的>10⁷ M⁻¹ s⁻¹到酪氨酸和谷胱甘肽的10³ - 10⁴ M⁻¹ s⁻¹。循环伏安法实验表明，Mn（IV）/Mn（III）电对的E1/2没有显著差异；因此，三种异构配合物的差异反应性是根据静电和空间效应来解释的。微摩尔浓度的MnTM - 2 - PyP在与ONOO⁻反应时能很好地与毫摩尔浓度的CO₂竞争，甚至可以清除一部分生成的ONOOCO₂⁻。通过被ONOO⁻和ONOOCO₂⁻快速氧化，并被抗坏血酸盐、尿酸盐和谷胱甘肽等抗氧化剂还原，这些锰卟啉，尤其是MnTM - 2 - PyP，可以将过氧亚硝酸盐的氧化电位转向天然抗氧化剂，从而保护更关键的靶标，如蛋白质和核酸。
