Catalytic scavenging of peroxynitrite by isomeric Mn(III) N-methylpyridylporphyrins in the presence of reductants
Catalytic scavenging of peroxynitrite by isomeric Mn(III) N-methylpyridylporphyrins in the presence of reductants
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DOI：
10.1021/tx980245d
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发表时间：
1999-05-01
影响因子：
4.1
通讯作者：
Radi, R
中科院分区：
文献类型：
--
作者：
Ferrer-Sueta, G;Batinic-Haberle, I;Radi, R
研究了5，10，15，20-四（N-甲基吡啶基）卟啉锰（MnTMPyP）的三种异构体与过氧亚硝酸根的反应。Mn（III）络合物与过氧亚硝酸根阴离子在37 ℃下反应，对于MnTM-2-PyP、MnTM-3-PyP和MnTM-4-PyP，速率常数分别为1.85 x 10（7）、3.82 x 10（6）和4.33 x 10（6）M-1 s（-1），以产生相应的氧代-Mn（IV）络合物。在5至8.5的pH范围内，MnTM-2-PyP的反应速度比其他两种异构体快5倍。的oxo-Mn（IV）络合物，可以反过来被还原谷胱甘肽，抗坏血酸，尿酸盐，或氧化酪氨酸。氧化-Mn（IV）络合物还原的速率常数范围从抗坏血酸的> 10（7）M-1 s（-1）到酪氨酸和谷胱甘肽的10（3）-10（4）M-1 s（-1）。循环伏安法实验表明，有没有显着的差异，在E-1/2的Mn（IV）Mn（III）对，因此，差分反应性的三个异构体配合物的静电和空间效应的解释。微摩尔浓度的MnTM-2-PyP在与ONOO-反应时与毫摩尔CO2竞争良好，并且它甚至可以取代形成的ONOOCO 2-的一部分。通过被ONOO-和ONOOCO 2-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潜力重新引导至天然抗氧化剂，从而保护更重要的目标，例如蛋白质和核酸。
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 E-1/2 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.