University of Zagreb, Faculty of Pharmacy and Biochemistry, Ante Kovačića 1, Zagreb 10000, Croatia.
Dalton Trans. 2013 Oct 1;42(41):14757-65. doi: 10.1039/c3dt50767j.
Growing interest in redox-active compounds as therapeutics for oxidative stress-related diseases led to the design of metalloporphyrins as some of the most potent functional SOD-mimics. Herein we report a detailed electrochemical study of the protolytic and redox equilibria of manganese ortho and meta substituted N-ethylpyridyl porphyrins (MnPs), MnTE-2-PyP(5+) and MnTE-3-PyP(5+), in aqueous solutions. The electrochemical parameters of redox processes for all experimentally available species have been determined, as well as their diffusion coefficients and estimated sizes of aqueous cavities. The results indicate that possible changes of the intracellular acidity cannot affect the antioxidant activity of MnPs in vivo, since no change in the E(Mn(III)P/Mn(II)P) values was observed below pH 10. Furthermore, the results confirm that both of these MnPs can be efficient redox scavengers of peroxynitrite (ONOO(-)), another major damaging species in vivo. This can occur by either single-electron reduction or two-electron reduction of ONOO(-), involving either the Mn(IV)P/Mn(III)P redox couple or Mn(IV)P/Mn(II)P redox couple. In addition to kred(ONOO(-)) reported previously, the thermodynamic parameters calculated herein imply a strong and identical driving force for the reaction of both ortho and meta isomeric MnPs with ONOO(-). An enlargement of both Mn(III)P complexes upon an increase of the solution pH was also observed and attributed to the reduction of positive charge on the central ion caused by deprotonation of the axial water molecules. This expansion of aqueous cavities suggests the formation of a solvent cage and the increased lipophilicity of Mn(III)P complexes caused by increased electron density on the Mn ion.
人们对氧化应激相关疾病的治疗中氧化还原活性化合物的兴趣日益浓厚,这导致了金属卟啉的设计,作为最有效的功能 SOD 模拟物之一。在此,我们报告了锰邻位和间位取代 N-乙基吡啶基卟啉(MnPs)、MnTE-2-PyP(5+)和 MnTE-3-PyP(5+)在水溶液中的质子化和氧化还原平衡的详细电化学研究。已经确定了所有实验可得物种的氧化还原过程的电化学参数,以及它们的扩散系数和估计的水腔尺寸。结果表明,细胞内酸度的可能变化不会影响 MnPs 在体内的抗氧化活性,因为在 pH 值低于 10 时,没有观察到 E(Mn(III)P/Mn(II)P)值的变化。此外,结果证实这两种 MnPs 都可以有效地作为过氧亚硝酸盐(ONOO(-))的还原清除剂,ONOO(-)是体内另一种主要的损伤性物质。这可以通过 ONOO(-)的单电子还原或双电子还原来实现,涉及 Mn(IV)P/Mn(III)P 氧化还原对或 Mn(IV)P/Mn(II)P 氧化还原对。除了先前报道的 kred(ONOO(-))之外,本文计算的热力学参数意味着邻位和间位异构体 MnPs 与 ONOO(-)的反应具有很强的相同驱动力。还观察到随着溶液 pH 值的增加,两种 Mn(III)P 配合物的增大,并归因于轴向水分子的去质子化导致中心离子上正电荷的减少。水腔的这种膨胀表明形成了溶剂笼,并且由于 Mn 离子上的电子密度增加,Mn(III)P 配合物的亲脂性增加。