Coordination chemistry of the Cu_Z site in nitrous oxide reductase and its synthetic mimics

Atmospheric nitrous oxide (N₂O) has garnered significant attention recently due to its dual roles as an ozone depletion agent and a potent greenhouse gas. Anthropogenic N₂O emissions occur primarily through agricultural disruption of nitrogen homeostasis causing N₂O to build up in the atmosphere. The enzyme responsible for N₂O fixation within the geochemical nitrogen cycle is nitrous oxide reductase (N₂OR), which catalyzes 2H⁺/2e^- reduction of N₂O to N₂ and H₂O at a tetranuclear active site, Cu_Z. In this review, the coordination chemistry of Cu_Z is reviewed. Recent advances in the understanding of biological Cu_Z coordination chemistry is discussed, as are significant breakthroughs in synthetic modeling of Cu_Z that have emerged in recent years. The latter topic includes both structurally faithful, synthetic [Cu₄(µ₄-S)] clusters that are able to reduce N₂O, as well as dicopper motifs that shed light on reaction pathways available to the critical Cu_I-Cu_IV cluster edge of Cu_Z. Collectively, these advances in metalloenzyme studies and synthetic model systems provide meaningful knowledge about the physiologically relevant coordination chemistry of Cu_Z but also open new questions that will pose challenges in the near future.