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The Zn(Cys)2(His)2 site of the anti-sigma factor ChrR reacts rapidly with 1O2 supporting its involvement in 1O2 sensing by this protein., All organisms have to cope with the deleterious effects of reactive oxygen species. Some of them are able to mount a transcriptional response to various oxidative stresses, which involves sensor proteins capable of assessing the redox status of the cell or to detect reactive oxygen species. In this article, we describe the design, synthesis and characterization of Zn·LASD(HHCC), a model for the Zn(Cys)2(His)2 zinc finger site of ChrR, a sensor protein involved in the bacterial defence against singlet oxygen that belongs to the family of zinc-binding anti-sigma factors possessing a characteristic H/C–X24/25–H–X3–C–X2–C motif. The 46-amino acid model peptide LASD(HHCC) was synthetized by solid phase peptide synthesis and its Zn2+-binding properties were investigated using electronic absorption, circular dichroism and NMR. LASD(HHCC) forms a 1 : 1 complex with Zn2+, namely Zn·LASD(HHCC), that adopts a well-defined conformation with the Zn2+ ion capping a 3-helix core that reproduces almost perfectly the fold of the ChrR in the vicinity of its zinc site. H2O2 reacts with Zn·LASD(HHCC) to yield a disulfide with a second order rate constant of 0.030 ± 0.002 M–1 s–1. Zn·LASD(HHCC) reacts rapidly with singlet oxygen to yield sulfinates and sulfonates. A lower limit of the chemical reaction rate constant between Zn·LASD(HHCC) and 1O2 was determined to be 3.9 × 106 M–1 s–1. Therefore, the Zn(Cys)2(His)2 site of Zn·LASD(HHCC) appears to be at least 5 times more reactive toward these two oxidants than that of a classical ββα zinc finger. Consequences for the activation mechanism of ChrR are discussed.

International audience; $ate$-iron(II) species such as [Ar$_3$Fe$^{ll}$]$^-$ (Ar = aryl) are key intermediates in Fe-catalyzed cross-coupling reactions between aryl Grignard reagents (ArMgX) and organic electrophiles. They can be active species in the catalytic cycle, or lead to Fe$^0$ and Fe$^I$ oxidation states.[l] In sorne cases, these low oxidation states can be themselves active in the coupling process.[2] However, their presence in the reaction medium most often leads to unwished organic byproducts. The development of new and efficient Fe-mediated cross-coupling processes therefore requires new frameworks enabling a fine control of the iron species distribution in the reaction medium, giving the possibility to inhibit the formation of unwanted oxidation states. So far, the formation of Fe$^0$ and Fe$^I$ species in cross-coupling mediums can be hardly controlled. A deep understanding of the formation mechanism of these oxidation states is thus fundamental if one wants to finely monitor their presence in the reaction medium. We report in this work our efforts related to the understanding of the elementary steps connecting ale [Ar$_3$Fe$^{ll}$]$^-$ species (Ar = Mes, Ph), formed by transmetallation of aryl Grignard reagents with FeCl$_2$, to the formation of Fe$^o$ and Fe$^l$ low oxidation states. A particular focus is put on the role of the steric and electronic effects of the aryl group in the reduction process. We demonstrate that a steric decompression induced by progressive substitution of the mesityl groups in [Mes$_3$Fe$^{ll}$$^- $ by phenyl anions leads to the formation of [Mes$_n$Ph$_{3-n}$Fe$^{II}$]$^-$ species (n = 0-2; observation by IH NMR). Thanks to this steric decompression, formation of Fe$^o$ and Fe$^l$ oxidation states is concomitantly observed by EPR and Méissbauer spectroscopies (Scheme 1).

High valent iron species are very reactive molecules involved in oxidation reactions of relevance to biology and chemical synthesis. Herein we describe iron(IV)–tosylimido complexes [FeIV(NTs)(MePy2tacn)](OTf)2 (1(IV)[double bond, length as m-dash]NTs) and [FeIV(NTs)(Me2(CHPy2)tacn)](OTf)2 (2(IV)[double bond, length as m-dash]NTs), (MePy2tacn = N-methyl-N,N-bis(2-picolyl)-1,4,7-triazacyclononane, and Me2(CHPy2)tacn = 1-(di(2-pyridyl)methyl)-4,7-dimethyl-1,4,7-triazacyclononane, Ts = Tosyl). 1(IV)[double bond, length as m-dash]NTs and 2(IV)[double bond, length as m-dash]NTs are rare examples of octahedral iron(IV)–imido complexes and are isoelectronic analogues of the recently described iron(IV)–oxo complexes [FeIV(O)(L)]2+ (L = MePy2tacn and Me2(CHPy2)tacn, respectively). 1(IV)[double bond, length as m-dash]NTs and 2(IV)[double bond, length as m-dash]NTs are metastable and have been spectroscopically characterized by HR-MS, UV-vis, 1H-NMR, resonance Raman, Mössbauer, and X-ray absorption (XAS) spectroscopy as well as by DFT computational methods. Ferric complexes [FeIII(HNTs)(L)]2+, 1(III)–NHTs (L = MePy2tacn) and 2(III)–NHTs (L = Me2(CHPy2)tacn) have been isolated after the decay of 1(IV)[double bond, length as m-dash]NTs and 2(IV)[double bond, length as m-dash]NTs in solution, spectroscopically characterized, and the molecular structure of [FeIII(HNTs)(MePy2tacn)](SbF6)2 determined by single crystal X-ray diffraction. Reaction of 1(IV)[double bond, length as m-dash]NTs and 2(IV)[double bond, length as m-dash]NTs with different p-substituted thioanisoles results in the transfer of the tosylimido moiety to the sulphur atom producing sulfilimine products. In these reactions, 1(IV)[double bond, length as m-dash]NTs and 2(IV)[double bond, length as m-dash]NTs behave as single electron oxidants and Hammett analyses of reaction rates evidence that tosylimido transfer is more sensitive than oxo transfer to charge effects. In addition, reaction of 1(IV)[double bond, length as m-dash]NTs and 2(IV)[double bond, length as m-dash]NTs with hydrocarbons containing weak C–H bonds results in the formation of 1(III)–NHTs and 2(III)–NHTs respectively, along with the oxidized substrate. Kinetic analyses indicate that reactions proceed via a mechanistically unusual HAT reaction, where an association complex precedes hydrogen abstraction.

The nature of the oxidizing species in water oxidation reactions with chemical oxidants (CAN and NaIO4), catalyzed by the pair of complexes α-[Fe(OTf)2(mcp)] (mcp = N,N′-dimethyl-N,N′-bis(pyridin-2-ylmethyl)cyclohexane-1,2-diamine, OTf = trifluoromethanesulfonate anion), (1) and -[Fe(OTf)2(mcp)], (1) has been investigated. Mössbauer spectroscopy provides definitive evidence that 1 and 1 generate oxoiron(IV) species α-[FeIV(O)(OH2)(mcp)]2+, (2) and -[FeIV(O)(OH2)(mcp)], (2) respectively, as the resting state, as early proposed on the basis of UV-Vis, resonance Raman and mass-spectrometry. Decomposition paths of the catalysts under experimental conditions of relevance to water oxidation catalysis have been investigated by identifying and quantifying ligand fragments that form upon catalyst degradation. This analysis correlates the water oxidation activity of 1 and 1 with stability against oxidative damage of the ligand via aliphatic C-H oxidation. The site of degradation and the relative stability against oxidative degradation is shown to be dependent on the topology of the catalyst. Furthermore, the mechanisms of catalyst degradation have been rationalized by computational analyses, which also explain why the topology of the catalyst enforces different oxidation sensitive sites. This information has served as the basis for creating a novel family of catalysts where sensitive C-H bonds have been replaced by C-D bonds. Consequently, deuterated analogs, D4--[Fe(OTf)2(mcp)] (D4-1) and D4--[Fe(OTf)2(mcp)] (D4-1, in which pseudobenzylic methylenic positions have been deuterated, and D6--[Fe(OTf)2(mcp)] (D6-1), where NMe groups are deuterated, were prepared. The catalytic activity of the deuterated analogs has been studied using CAN as terminal oxidant. D4-1 proves to be an extraordinarily active and efficient catalyst (up to 91% of O2 yield); it exhibits initial reaction rates identical to its protio analogue, but it is substantially more robust towards oxidative degradation and yields up to 2700 TON (n(O2)/n(Fe)), which constitutes the highest value described for a first row transition metal catalyst. Altogether evidence that the water oxidation catalytic activity is performed by a well-defined coordination complex and not by iron oxides formed after oxidative degradation of the ligands.