Jagnyesh K Satpathy, Rolly Yadav, Payal Panwar, Vijaya Thangaraj, Maheswaran Shanmugam, Chivukula V Sastri, Sam P de Visser
{"title":"硫连接铁(III)-烷基过氧反应性的机理差异:醛氧化优于脱甲酰化。","authors":"Jagnyesh K Satpathy, Rolly Yadav, Payal Panwar, Vijaya Thangaraj, Maheswaran Shanmugam, Chivukula V Sastri, Sam P de Visser","doi":"10.1002/anie.202512839","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":520556,"journal":{"name":"Angewandte Chemie (International ed. in English)","volume":" ","pages":"e202512839"},"PeriodicalIF":16.9000,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Mechanistic Divergence in Sulfur-Ligated Iron(III)-Alkylperoxo Reactivity: Aldehyde Oxidation Prevails over Deformylation.\",\"authors\":\"Jagnyesh K Satpathy, Rolly Yadav, Payal Panwar, Vijaya Thangaraj, Maheswaran Shanmugam, Chivukula V Sastri, Sam P de Visser\",\"doi\":\"10.1002/anie.202512839\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":520556,\"journal\":{\"name\":\"Angewandte Chemie (International ed. in English)\",\"volume\":\" \",\"pages\":\"e202512839\"},\"PeriodicalIF\":16.9000,\"publicationDate\":\"2025-09-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Angewandte Chemie (International ed. in English)\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1002/anie.202512839\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Angewandte Chemie (International ed. in English)","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1002/anie.202512839","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Mechanistic Divergence in Sulfur-Ligated Iron(III)-Alkylperoxo Reactivity: Aldehyde Oxidation Prevails over Deformylation.
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.