韩国梨花女子大学Wonwoo Nam团队报道了合成铁（III）-过氧中间体和Rieske双加氧酶的顺式二羟基化——实验和理论方法揭示了关键的O-O键激活步骤。相关研究成果发表在2024年10月22日出版的《美国化学会杂志》。

含铁酶和仿生化合物激活二氧（O₂）会产生铁-氧中间体，如铁超氧、-过氧、-过氧化氢和-氧，这些中间体介导生物和非生物系统中的氧化反应。在铁-氧中间体中，过氧化铁（III）物种作为氧化反应中的活性中间体不太常见。

该文中，研究人员对合成的单核非血红素铁-过氧化物中间体介导的，顺式二羟基化反应进行了实验和理论研究，证明了支持配体和金属中心在激活过氧化物配体，以实现顺式二羟化反应的O-O键均裂中的重要性。研究发现[Fe^III(O₂)(n-TMC)]⁺ (TMC =四甲基化四氮杂环烷烃；n=12、13和14）中TMC配体的环尺寸，对顺式二羟基化反应顺序有显著影响，[Fe^III(O₂)(12-TMC)]⁺ > [Fe^III(O₂)(13-TMC)]⁺ > [Fe^III(O₂)(14-TMC)]⁺。

此外，发现只有[Fe^III(O₂)(n-TMC)]⁺对烯烃的顺式二羟基化具有反应性，而不包括其他金属过氧化物络合物如[M^III(O₂)(n-TMC)]⁺ (M = Mn, Co, and Ni)。利用密度泛函理论（DFT）计算，研究发现电子从Fe dxz轨道转移到peroxoσ*（O-O）轨道有助于O-O键的均裂，O-O键断裂势垒与dxz和σ*（O-O）的前沿分子轨道之间的能隙密切相关。

进一步的计算研究表明，合成的[FeIII(O2)(12-TMC)]+复合物的反应性，与Rieske双加氧酶在顺二羟基化中的反应性相当，为Fe（III）-过氧化物物种可能参与Rieske二加氧酶提供了令人信服的证据。

研究结果显著提高了人们对Rieske双加氧酶，和合成非血红素铁过氧化物模型顺式二羟基化机制的理解。

附：英文原文

Title: cis-Dihydroxylation by Synthetic Iron(III)–Peroxo Intermediates and Rieske Dioxygenases: Experimental and Theoretical Approaches Reveal the Key O–O Bond Activation Step

Author: Peng Wu, Wenjuan Zhu, Yanru Chen, Zikuan Wang, Akhilesh Kumar, Binju Wang, Wonwoo Nam

Issue&Volume: October 22, 2024

Abstract: Dioxygen (O2) activation by iron-containing enzymes and biomimetic compounds generates iron–oxygen intermediates, such as iron-superoxo, -peroxo, -hydroperoxo, and -oxo, that mediate oxidative reactions in biological and abiological systems. Among the iron–oxygen intermediates, iron(III)–peroxo species are less frequently implicated as active intermediates in oxidation reactions. In this study, we present the combined experimental and theoretical investigations on cis-dihydroxylation reactions mediated by synthetic mononuclear nonheme iron–peroxo intermediates, demonstrating the importance of supporting ligands and metal centers in activating the peroxo ligand toward the O–O bond homolysis for the cis-dihydroxylation reactions. We found a significant ring size effect of the TMC ligand in [FeIII(O2)(n-TMC)]+ (TMC = tetramethylated tetraazacycloalkane; n = 12, 13, and 14) on the cis-dihydroxylation reactivity order: [FeIII(O2)(12-TMC)]+ > [FeIII(O2)(13-TMC)]+ > [FeIII(O2)(14-TMC)]+. Additionally, we found that only [FeIII(O2)(n-TMC)]+, but not other metal–peroxo complexes such as [MIII(O2)(n-TMC)]+ (M = Mn, Co, and Ni), is reactive for the cis-dihydroxylation of olefins. Using density functional theory (DFT) calculations, we revealed that electron transfer from the Fe dxz orbital to the peroxo σ*(O–O) orbital facilitates the O–O bond homolysis, with the O–O bond cleavage barrier well correlated with the energy gap between the frontier molecular orbitals of dxz and σ*(O–O). Further computational studies showed that the reactivity of the synthetic [FeIII(O2)(12-TMC)]+ complex is comparable to that of Rieske dioxygenases in cis-dihydroxylation, providing compelling evidence of the potential involvement of Fe(III)–peroxo species in Rieske dioxygenases. Thus, the present results significantly advance our understanding of the cis-dihydroxylation mechanisms by Rieske dioxygenases and synthetic nonheme iron–peroxo models.

DOI: 10.1021/jacs.4c09354

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.4c09354