Department of Chemistry and Biochemistry, University of Oklahoma, 620 Parrington Oval, Norman, Oklahoma 73019, USA.
Inorg Chem. 2010 Jul 19;49(14):6253-66. doi: 10.1021/ic902423v.
Nitric oxide (NO) and its derivatives such as nitrite and hyponitrite are biologically important species of relevance to human health. Much of their physiological relevance stems from their interactions with the iron centers in heme proteins. The chemical reactivities displayed by the heme-NOx species (NOx = NO, nitrite, hyponitrite) are a function of the binding modes of the NOx ligands. Hence, an understanding of the types of binding modes extant in heme-NOx compounds is important if we are to unravel the inherent chemical properties of these NOx metabolites. In this Forum Article, the experimentally characterized linkage isomers of heme-NOx models and proteins are presented and reviewed. Nitrosyl linkage isomers of synthetic iron and ruthenium porphyrins have been generated by photolysis at low temperatures and characterized by spectroscopy and density functional theory calculations. Nitrite linkage isomers in synthetic metalloporphyrin derivatives have been generated from photolysis experiments and in low-temperature matrices. In the case of nitrite adducts of heme proteins, both N and O binding have been determined crystallographically, and the role of the distal H-bonding residue in myoglobin in directing the O-binding mode of nitrite has been explored using mutagenesis. To date, only one synthetic metalloporphyrin complex containing a hyponitrite ligand (displaying an O-binding mode) has been characterized by crystallography. This is contrasted with other hyponitrite binding modes experimentally determined for coordination compounds and computationally for NO reductase enzymes. Although linkage isomerism in heme-NOx derivatives is still in its infancy, opportunities now exist for a detailed exploration of the existence and stabilities of the metastable states in both heme models and heme proteins.
一氧化氮（NO）及其衍生物，如亚硝酸盐和次亚硝酸盐，是与人类健康相关的具有重要生物学意义的物质。它们的大部分生理相关性源于它们与血红素蛋白中铁中心的相互作用。血红素-NOx 物种（NOx=NO、亚硝酸盐、次亚硝酸盐）的化学反应性是 NOx 配体结合方式的函数。因此，如果我们要揭示这些 NOx 代谢物的固有化学性质，了解血红素-NOx 化合物中存在的结合模式类型就很重要。在这篇论坛文章中，介绍并回顾了血红素-NOx 模型和蛋白质的实验表征的键合异构体。通过低温光解生成了合成铁和钌卟啉的亚硝酰键异构体，并通过光谱和密度泛函理论计算进行了表征。通过光解实验和低温基质中生成了合成金属卟啉衍生物中的亚硝酸盐键异构体。在血红素蛋白的亚硝酸盐加合物的情况下，通过晶体学确定了 N 和 O 的结合，并用突变研究探索了肌红蛋白中远端氢键残基在指导亚硝酸盐 O 结合模式中的作用。迄今为止，只有一个含有次亚硝酸盐配体（显示 O 结合模式）的合成金属卟啉配合物通过晶体学进行了表征。这与其他次亚硝酸盐结合模式形成鲜明对比，这些结合模式已经在配位化合物中通过实验确定，并通过计算确定了 NO 还原酶中的结合模式。尽管血红素-NOx 衍生物中的键合异构体仍处于起步阶段，但现在有机会详细探索血红素模型和血红素蛋白中亚稳态的存在和稳定性。
