Hubei Provincial Key Laboratory of Bioinorganic Chemistry and Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan 430074, P. R. China.
Metallomics. 2021 Mar 17;13(3). doi: 10.1093/mtomcs/mfab005.
Understanding the toxicological properties of MnIII-porphyrins (MnTPPS, MnTMPyP, or MnTBAP) can provide important biochemical rationales in developing them as the therapeutic drugs against protein tyrosine nitration-induced inflammation diseases. Here, we present a comprehensive understanding of the pH-dependent redox behaviors of these MnIII-porphyrins and their structural effects on catalyzing bovine serum albumin (BSA) nitration in the presence of H2O2 and NO2-. It was found that both MnTPPS and MnTBAP stand out in catalyzing BSA nitration at physiologically close condition (pH 8), yet they are less effective at pH 6 and 10. MnTMPyP was shown to have no ability to catalyze BSA nitration under all tested pHs (pH 6, 8, and 10). The kinetics and active intermediate determination through electrochemistry method revealed that both the pH-dependent redox behavior of the central metal cation and the antioxidant capability of porphin derivative contribute to the catalytic activities of three MnIII-porphyrins in BSA nitration in the presence of H2O2/NO2-. These comprehensive studies on the oxidative reactivity of MnIII-porphyrins toward BSA nitration may provide new clues for searching the manganese-based therapeutic drugs against the inflammation-related diseases.
了解 MnIII-卟啉（MnTPPS、MnTMPyP 或 MnTBAP）的毒理学特性可以为将它们开发为治疗蛋白酪氨酸硝化诱导的炎症性疾病的药物提供重要的生化依据。在这里，我们全面了解了这些 MnIII-卟啉在 pH 依赖性氧化还原行为及其对在 H2O2 和 NO2-存在下催化牛血清白蛋白（BSA）硝化的结构影响。结果发现，MnTPPS 和 MnTBAP 在生理相近条件（pH 8）下均能突出地催化 BSA 硝化，但在 pH 6 和 10 时效果较差。MnTMPyP 在所有测试的 pH 值（pH 6、8 和 10）下均显示出没有催化 BSA 硝化的能力。通过电化学方法进行的动力学和活性中间体测定表明，中心金属阳离子的 pH 依赖性氧化还原行为和卟啉衍生物的抗氧化能力都有助于三种 MnIII-卟啉在 H2O2/NO2-存在下催化 BSA 硝化的催化活性。这些对 MnIII-卟啉对 BSA 硝化的氧化反应性的综合研究可能为寻找针对炎症相关疾病的基于锰的治疗药物提供新线索。
