Zhang Ting Ting, Liu Yong Dong, Zhong Ru Gang
College of Life Science & Bioengineering, Beijing University of Technology, Beijing 100124, PR China.
College of Life Science & Bioengineering, Beijing University of Technology, Beijing 100124, PR China.
J Inorg Biochem. 2015 Sep;150:126-32. doi: 10.1016/j.jinorgbio.2015.06.005. Epub 2015 Jun 22.
Nitrite reduction to nitric oxide by heme proteins was reported as a protective mechanism to hypoxic injury in mammalian physiology. In this study, the pathways of nitrite reduction to nitric oxide mediated by iron(II) porphyrin (P) complexes, which were generally recognized as models for heme proteins, were investigated by using density functional theory (DFT). In view of two type isomers of combination of nitrite and Fe(II)(P), N-nitro- and O-nitrito-Fe(II)-porphyrin complexes, and two binding sites of proton to the different O atoms of nitrite moiety, four main pathways for the conversion of nitrite into nitric oxide mediated by iron(II) porphyrins were proposed. The results indicate that the pathway of N-bound Fe(II)(P)(NO2) isomer into Fe(III)(P)(NO) and water is similar to that of O-bound isomer into nitric oxide and Fe(III)(P)(OH) in both thermodynamical and dynamical aspects. Based on the initial computational studies of five-coordinate nitrite complexes, the conversion of nitrite into NO mediated by Fe(II)(P)(L) complexes with 14 kinds of proximal ligands was also investigated. Generally, the same conclusion that the pathways of N-bound isomers are similar to those of O-bound isomer was obtained for iron(II) porphyrin with ligands. Different effects of ligands on the reduction reactions were also found. It is notable that the negative proximal ligands can improve reactive abilities of N-nitro-iron(II) porphyrins in the conversion of nitrite into nitric oxide compared to neutral ligands. The findings will be helpful to expand our understanding of the mechanism of nitrite reduction to nitric oxide by iron(II) porphyrins.
血红素蛋白将亚硝酸盐还原为一氧化氮被报道为哺乳动物生理学中对缺氧损伤的一种保护机制。在本研究中，通过使用密度泛函理论（DFT）研究了由铁（II）卟啉（P）配合物介导的亚硝酸盐还原为一氧化氮的途径，铁（II）卟啉配合物通常被认为是血红素蛋白的模型。鉴于亚硝酸盐与Fe（II）（P）组合的两种类型异构体，即N-硝基和O-亚硝基-Fe（II）-卟啉配合物，以及质子与亚硝酸盐部分不同O原子的两个结合位点，提出了铁（II）卟啉介导的亚硝酸盐转化为一氧化氮的四条主要途径。结果表明，N键合的Fe（II）（P）（NO2）异构体转化为Fe（III）（P）（NO）和水的途径在热力学和动力学方面都与O键合异构体转化为一氧化氮和Fe（III）（P）（OH）的途径相似。基于对五配位亚硝酸盐配合物的初步计算研究，还研究了由具有14种近端配体的Fe（II）（P）（L）配合物介导的亚硝酸盐向NO的转化。通常，对于带有配体的铁（II）卟啉，得到了相同的结论，即N键合异构体的途径与O键合异构体的途径相似。还发现了配体对还原反应的不同影响。值得注意的是，与中性配体相比，负性近端配体可以提高N-硝基-铁（II）卟啉在亚硝酸盐转化为一氧化氮过程中的反应能力。这些发现将有助于扩展我们对铁（II）卟啉将亚硝酸盐还原为一氧化氮机制的理解。
