The Role of Iron‐Hyponitrite Intermediates in Biology and Insights From Synthetic Model Complexes

ABSTRACT Nitric oxide reductases (NORs) are a class of metalloenzymes that are known to mediate the 2 e − / 2 H + reduction of nitric oxide (NO) to nitrous oxide (N 2 O). There are three known types of NOR enzymes, each using a different iron‐based active site to mediate NO reduction. Despite the difference in active site architecture across NORs, NO reduction is expected to be linked by a common intermediate: hyponitrite (N 2 O 2 2− ). However, experimentally, very little is known about the expected Fe‐hyponitrite intermediates. In this Perspective, we provide a detailed discussion of Fe‐hyponitrite chemistry. We start with an introduction into NOR metalloenzymes and provide a detailed account of the known and proposed steps of catalytic NO reduction by these enzymes with a specific focus on the proposed Fe‐hyponitrite intermediates. We then turn our focus on what is known about synthetic Fe‐hyponitrite complexes. We introduce hyponitrite as a ligand and discuss sources of preformed hyponitrite. We then introduce the three known Fe‐hyponitrite complexes and discuss how these relate to NO reduction in NORs. Finally, we summarize what is known about Fe‐hyponitrite chemistry and give an outlook on the aspects of this chemistry that are still vastly underexplored.