Beijing National Laboratory for Molecular Sciences (BNLMS), CAS Key Laboratory of Photochemistry, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences , Beijing 100190, P. R. China.
University of Chinese Academy of Sciences , Beijing 100049, P. R. China.
J Am Chem Soc. 2017 Sep 20;139(37):13038-13046. doi: 10.1021/jacs.7b06343. Epub 2017 Sep 8.
AurF and CmlI are currently the only two known diiron arylamine oxygenases. On the basis of extensive quantum mechanical/molecular mechanical (QM/MM) spectroscopic and mechanistic modelings, here we predict that the key oxygenated intermediates in AurF and CmlI, so-called P, are uniformly hydroperoxo species having similar structures. As a basis for mechanistic unification in AurF and CmlI, the proposed diferric-hydroperoxo P is calculated to be able to promote the arylamine N-oxygenation with highly accessible kinetics. This convergent μ-η:η structural assignment of P's in AurF and CmlI can rationalize many conundrums for P, including the different Mössbauer spectroscopic parameters, low O-O vibrational frequency, ambiphilic reactivity, and inertness toward C-H activation. In view of the very limited knowledge about hydroperoxo species in diiron enzymes, the novel diferric-hydroperoxo-mediated N-oxygenation mechanism revealed in this work opens up a new avenue for understanding the O activation mode in nature. For elucidating the structures of transient oxidants for diiron enzymes, the promising approach of QM/MM Mössbauer spectroscopic modeling is highlighted as a key problem solver in mechanistic enzymatic research.
AurF 和 CmlI 是目前仅有的两种已知的二铁芳胺加氧酶。基于广泛的量子力学/分子力学（QM/MM）光谱和机理建模，我们在这里预测，AurF 和 CmlI 中的关键含氧中间体，即所谓的 P，均为具有相似结构的统一过氧氢物种。作为 AurF 和 CmlI 中机理统一的基础，所提出的双核铁过氧氢 P 被计算为能够以可接近的动力学促进芳胺的 N-氧化。在 AurF 和 CmlI 中 P 的这种收敛的 μ-η:η 结构分配可以合理化 P 的许多难题，包括不同的穆斯堡尔光谱参数、低 O-O 振动频率、两性反应性以及对 C-H 活化的惰性。鉴于关于二铁酶中过氧氢物种的知识非常有限，本工作揭示的新型双核铁过氧氢介导的 N-氧化机制为理解自然界中的 O 激活模式开辟了新途径。为了阐明二铁酶中瞬态氧化剂的结构，QM/MM 穆斯堡尔光谱建模这一很有前途的方法被突出为机理酶学研究中的关键问题解决者。
