Satpathy Jagnyesh K, Yadav Rolly, Panwar Payal, Thangaraj Vijaya, Shanmugam Maheswaran, Sastri Chivukula V, de Visser Sam P
Department of Chemistry, Indian Institute of Technology, Guwahati, Assam, 781039, India.
Department of Chemistry, Indian Institute of Technology, Bombay, Powai, Mumbai, Maharashtra, 400076, India.
Angew Chem Int Ed Engl. 2025 Sep 4:e202512839. doi: 10.1002/anie.202512839.
Metalloenzymes activate molecular oxygen within their catalytic cycles to generate a reactive species capable of substrate transformation. In many iron-containing enzymes, it is a high-valent iron(IV)-oxo complex that is synthesized from an iron(III)-alkylperoxo intermediate, although direct observation and characterization of such species have remained elusive, leaving their mechanistic role uncertain. To address this gap in our understanding, we present here the synthesis, comprehensive characterization, and reactivity of a novel thioether-ligated iron(III)-alkylperoxo complex supported by the ligand 2-((2-(pyridin-2-yl)ethyl)thio)-N,N-bis(pyridin-2-ylmethyl)ethan-1-amine. Characterization was done using UV-vis spectroscopy, resonance Raman spectroscopy, electron paramagnetic resonance spectroscopy, and electrospray ionization mass spectrometry. Reactivity studies reveal that this complex exhibits electrophilic oxidation of model substrates, including dimethylsulfide, triphenylphosphine, and cyclohexanecarboxaldehyde. Notably, the latter substrate reacts via the unusual aldehyde C─H bond abstraction leading to cyclohexanecarboxylic acid, which is explained by favorable aldehyde C─H abstraction transition states due to stabilizing interactions between the ligand framework and the substrate. Moreover, the reaction is initiated with a homolytic O─O bond cleavage in the iron(III)-alkylperoxo group that yields a reactive iron(IV)-oxo species that mediates substrate oxidation. To our knowledge, this work represents the first example of a mononuclear low-spin (S = ½) nonheme iron(III)-alkylperoxo complex displaying such unprecedented electrophilic reactivity.
金属酶在其催化循环中激活分子氧,以生成能够进行底物转化的活性物种。在许多含铁酶中,是由铁(III)-烷基过氧中间体合成的高价铁(IV)-氧络合物,尽管对这类物种的直接观察和表征仍然难以实现,其作用机制也尚不确定。为了填补我们在理解上的这一空白,我们在此展示了一种由配体2-((2-(吡啶-2-基)乙基)硫代)-N,N-双(吡啶-2-基甲基)乙胺支持的新型硫醚连接的铁(III)-烷基过氧络合物的合成、全面表征及反应活性。使用紫外可见光谱、共振拉曼光谱、电子顺磁共振光谱和电喷雾电离质谱进行表征。反应活性研究表明,该络合物对包括二甲硫醚、三苯基膦和环己烷甲醛在内的模型底物表现出亲电氧化作用。值得注意的是,后一种底物通过不寻常的醛C─H键提取反应生成环己烷羧酸,这是由于配体骨架与底物之间的稳定相互作用导致有利的醛C─H提取过渡态来解释的。此外,反应始于铁(III)-烷基过氧基团中的均裂O─O键断裂,生成介导底物氧化的活性铁(IV)-氧物种。据我们所知,这项工作代表了单核低自旋(S = ½)非血红素铁(III)-烷基过氧络合物展现出这种前所未有的亲电反应活性的首个实例。