Myoglobin-Catalyzed Azide Reduction Proceeds via an Anionic Metal Amide Intermediate,Journal of the American Chemical Society

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Myoglobin-Catalyzed Azide Reduction Proceeds via an Anionic Metal Amide Intermediate
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2024-01-09 , DOI: 10.1021/jacs.3c09279
Matthias Tinzl ₁ , Johannes V Diedrich ₂ , Peer R E Mittl ₃ , Martin Clémancey ₄ , Markus Reiher ₅ , Jonny Proppe ₂ , Jean-Marc Latour ₄ , Donald Hilvert ₁

Affiliation

Nitrene transfer reactions catalyzed by heme proteins have broad potential for the stereoselective formation of carbon–nitrogen bonds. However, competition between productive nitrene transfer and the undesirable reduction of nitrene precursors limits the broad implementation of such biocatalytic methods. Here, we investigated the reduction of azides by the model heme protein myoglobin to gain mechanistic insights into the factors that control the fate of key reaction intermediates. In this system, the reaction proceeds via a proposed nitrene intermediate that is rapidly reduced and protonated to give a reactive ferrous amide species, which we characterized by UV/vis and Mössbauer spectroscopies, quantum mechanical calculations, and X-ray crystallography. Rate-limiting protonation of the ferrous amide to produce the corresponding amine is the final step in the catalytic cycle. These findings contribute to our understanding of the heme protein-catalyzed reduction of azides and provide a guide for future enzyme engineering campaigns to create more efficient nitrene transferases. Moreover, harnessing the reduction reaction in a chemoenzymatic cascade provided a potentially practical route to substituted pyrroles.

中文翻译：

肌红蛋白催化的叠氮化物还原通过阴离子金属酰胺中间体进行

由血红素蛋白催化的硝酸转移反应在碳-氮键的立体选择性形成方面具有广泛的潜力。然而，生产性硝烯转移与不良的硝烯前体还原之间的竞争限制了这种生物催化方法的广泛实施。在这里，我们研究了模型血红素蛋白肌红蛋白对叠氮化物的还原，以获得对控制关键反应中间体命运的因素的机制见解。在该系统中，反应通过拟议的硝烯中间体进行，该中间体被快速还原和质子化，得到反应性亚铁酰胺物种，我们通过 UV/Vis 和 Mössbauer 光谱、量子力学计算和 X 射线晶体学对其进行表征。亚铁酰胺的限速质子化以产生相应的胺是催化循环的最后一步。这些发现有助于我们了解血红素蛋白催化的叠氮化物还原，并为未来的酶工程活动提供指导，以创造更有效的硝酸转移酶。此外，利用化学酶级联反应中的还原反应为取代吡咯提供了一种潜在的实用途径。

更新日期：2024-01-09

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