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Abstract Flavodiiron NO reductases (FNORs) are important enzymes in microbial pathogenesis, as they equip microbes with resistance to the human immune defense agent nitric oxide (NO). Despite many efforts, intermediates that would provide insight into how the non‐heme diiron active sites of FNORs reduce NO to N2O could not be identified. Computations predict that iron‐hyponitrite complexes are the key species, leading from NO to N2O. However, the coordination chemistry of non‐heme iron centers with hyponitrite is largely unknown. In this study, we report the reactivity of two non‐heme iron complexes with preformed hyponitrite. In the case of [Fe(TPA)(CH3CN)2](OTf)2, cleavage of hyponitrite and formation of an Fe2(NO)2diamond core is observed. With less Lewis‐acidic [Fe2(BMPA‐PhO)2(OTf)2] (2), reaction with Na2N2O2in polar aprotic solvent leads to the formation of a red complex,3. X‐ray crystallography shows that3is a tetranuclear iron‐hyponitrite complex, [{Fe2(BMPA‐PhO)2}2(μ‐N2O2)](OTf)2, with a unique hyponitrite binding mode. This species provided the unique opportunity to us to study the interaction of hyponitrite with non‐heme iron centers and the reactivity of the bound hyponitrite ligand. Here, either protonation or oxidation of3is found to induce N2O formation, supporting the hypothesis that hyponitrite is a viable intermediate in NO reduction.
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Secondary Sphere Lewis Acid Activated Heme Superoxo Adducts Mimic Crucial Non‐Covalent Interactions in IDO/TDO Heme Dioxygenases
Abstract Heme enzymes play a central role in a medley of reactivities within a wide variety of crucial biological systems. Their active sites are highly decorated with pivotal evolutionarily optimized non‐covalent interactions that precisely choreograph their biological functionalities with specific regio‐, stereo‐, and chemo‐selectivities. Gaining a clear comprehension of how such weak interactions within the active sites control reactivity offers powerful information to be implemented into the design of future therapeutic agents that target these heme enzymes. To shed light on such critical details pertaining to tryptophan dioxygenating heme enzymes, this study investigates the indole dioxygenation reactivities of Lewis acid‐activated heme superoxo model systems, wherein an unprecedented kinetic behavior is revealed. In that, the activated heme superoxo adduct is observed to undergo indole dioxygenation with the intermediacy of a non‐covalently organized precursor complex, which forms prior to the rate‐limiting step of the overall reaction landscape. Spectroscopic and theoretical characterization of this precursor complex draws close parallels to the ternary complex of heme dioxygenases, which has been postulated to be of crucial importance for successful 2,3‐dioxygenative cleavage of indole moieties.
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- PAR ID:
- 10554798
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Chemistry – A European Journal
- Volume:
- 30
- Issue:
- 68
- ISSN:
- 0947-6539
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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