Effect of monodentate heterocycle co-ligands on the µ-1,2-peroxo-diiron(III) mediated aldehyde deformylation reactions.

Peroxo-diiron(III) species are present in the active sites of many metalloenzymes that carry out challenging organic transformations. The reactivity of these species is influenced by various factors, such as the structure and topology of the supporting ligands, the identity of the axial and equatorial co-ligands, and the oxidation states of the metal ion(s). In this study, we aim to diversify the importance of equatorial ligands in controlling the reactivity of peroxo-diiron(III) species. As a model compound, we chose the previously published and fully characterized [(PBI)2(CH3CN)FeIII(µ-O2)FeIII(CH3CN)(PBI)2]4+ complex, where the steric effect of the four PBI ligands is minimal, so the labile CH3CN molecules easily can be replaced by different monodentate co-ligands (substituted pyridines and N-donor heterocyclic compounds). Thus, their effect on the electronic and spectral properties of peroxo-divas(III) intermediates could be easily investigated. The relationship between structure and reactivity was also investigated in the stoichiometric deformylation of PPA mediated by peroxo-diiron(III) complexes. It was found that the deformylation rates are influenced by the Lewis acidity and redox properties of the metal centers, and showed a linear correlation with the FeIII/FeII redox potentials (in the range of 197 to 415 mV).

Mechanisms of Sulfoxidation and Epoxidation Mediated by Iron(III)-Iodosylbenzene Adduct: Electron-Transfer vs. Oxygen-Transfer Mechanism.

The mechanisms of sulfoxidation and epoxidation mediated by previously synthesized and characterized iron(III)-iodosylbenzene adduct, FeIII(OIPh) were investigated using para-substituted thioanisole and styrene derivatives as model substrates. Based on detailed kinetic reaction experiments, including the linear free-energy relationships between the relative reaction rates (logkrel) and the σp (4R-PhSMe) with ρ = -0.65 (catalytic) and ρ = -1.13 (stoichiometric), we obtained strong evidence that the stoichiometric and catalytic oxidation of thioanisoles mediated by FeIII(OIPh) species involves direct oxygen transfer. The small negative slope -2.18 from log kobs versus Eox for 4R-PhSMe gives further clear evidence for the direct oxygen atom transfer mechanism. On the contrary, with the linear free-energy relationships between the relative reaction rates (logkrel) and total substituent effect (TE, 4R-PhCHCH2) parameters with slope = 0.33 (catalytic) and 2.02 (stoichiometric), the stoichiometric and catalytic epoxidation of styrenes takes place through a nonconcerted electron transfer (ET) mechanism, including the formation of the radicaloid benzylic radical intermediate in the rate-determining step. On the basis of mechanistic studies, we came to the conclusion that the title iron(III)-iodosylbenzene complex is able to oxygenate sulfides and alkenes before it is transformed into the oxo-iron form by cleavage of the O-I bond.

Effect of Redox Potential on Diiron-Mediated Disproportionation of Hydrogen Peroxide.

Heme and nonheme dimanganese catalases are widely distributed in living organisms to participate in antioxidant defenses that protect biological systems from oxidative stress. The key step in these processes is the disproportionation of H2O2 to O2 and water, which can be interpreted via two different mechanisms, namely via the formation of high-valent oxoiron(IV) and peroxodimanganese(III) or diiron(III) intermediates. In order to better understand the mechanism of this important process, we have chosen such synthetic model compounds that can be used to map the nature of the catalytically active species and the factors influencing their activities. Our previously reported µ-1,2-peroxo-diiron(III)-containing biomimics are good candidates, as both proposed reactive intermediates (FeIVO and FeIII2(µ-O2)) can be derived from them. Based on this, we have investigated and compared five heterobidentate-ligand-containing model systems including the previously reported and fully characterized [FeII(L1-4)3]2+ (L1 = 2-(2'-pyridyl)-1H-benzimidazole, L2 = 2-(2'-pyridyl)-N-methyl-benzimidazole, L3 = 2-(4-thiazolyl)-1H-benzimidazole and L4 = 2-(4'-methyl-2'-pyridyl)-1H-benzimidazole) and the novel [FeII(L5)3]2+ (L5 = 2-(1H-1,2,4-triazol-3-yl)-pyridine) precursor complexes with their spectroscopically characterized µ-1,2-peroxo-diiron(III) intermediates. Based on the reaction kinetic measurements and previous computational studies, it can be said that the disproportionation reaction of H2O2 can be interpreted through the formation of an electrophilic oxoiron(IV) intermediate that can be derived from the homolysis of the O-O bond of the forming µ-1,2-peroxo-diiron(III) complexes. We also found that the disproportionation rate of the H2O2 shows a linear correlation with the FeIII/FeII redox potential (in the range of 804 mV-1039 mV vs. SCE) of the catalysts controlled by the modification of the ligand environment. Furthermore, it is important to note that the two most active catalysts with L3 and L5 ligands have a high-spin electronic configuration.

Stoichiometric Alkane and Aldehyde Hydroxylation Reactions Mediated by In Situ Generated Iron(III)-Iodosylbenzene Adduct.

Previously synthesized and spectroscopically characterized mononuclear nonheme, low-spin iron(III)-iodosylbenzene complex bearing a bidentate pyridyl-benzimidazole ligands has been investigated in alkane and aldehyde oxidation reactions. The in situ generated Fe(III) iodosylbenzene intermediate is a reactive oxidant capable of activating the benzylic C-H bond of alkane. Its electrophilic character was confirmed by using substituted benzaldehydes and a modified ligand framework containing electron-donating (Me) substituents. Furthermore, the results of kinetic isotope experiments (KIE) using deuterated substrate indicate that the C-H activation can be interpreted through a tunneling-like HAT mechanism. Based on the results of the kinetic measurements and the relatively high KIE values, we can conclude that the activation of the C-H bond mediated by iron(III)-iodosylbenzene adducts is the rate-determining step.

Influence of Equatorial Co-Ligands on the Reactivity of LFeIIIOIPh.

Previous biomimetic studies clearly proved that equatorial ligands significantly influence the redox potential and thus the stability/reactivity of biologically important oxoiron intermediates; however, no such studies were performed on FeIIIOIPh species. In this study, the influence of substituted pyridine co-ligands on the reactivity of iron(III)-iodosylbenzene adduct has been investigated in sulfoxidation and epoxidation reactions. Selective oxidation of thioanisole, cis-cyclooctene, and cis- and trans-stilbene in the presence of a catalytic amount of [FeII(PBI)3](OTf)2 with PhI(OAc)2 provide products in good to excellent yields through an FeIIIOIPh intermediate depending on the co-ligand (4R-Py) used. Several mechanistic studies were performed to gain more insight into the mechanism of oxygen atom transfer (OAT) reactions to support the reactive intermediate and investigate the effect of the equatorial co-ligands. Based on competitive experiments, including a linear free-energy relationship between the relative reaction rates (logkrel) and the σp (4R-Py) parameters, strong evidence has been observed for the electrophilic character of the reactive species. The presence of the [(PBI)2(4R-Py)FeIIIOIPh]3+ intermediates and the effect of the co-ligands was also supported by UV-visible measurements, including the color change from red to green and the hypsochromic shifts in the presence of co-ligands. This is another indication that the title iron(III)-iodosylbenzene adduct is able to oxygenate sulfides and alkenes before it is transformed into the oxoiron form by cleavage of the O-I bond.

Catalytic and Stoichiometric Baeyer-Villiger Oxidation Mediated by Nonheme Peroxo-Diiron(III), Acylperoxo, and Iodosylbenzene Iron(III) Intermediates.

In this paper we describe a detailed mechanistic studies on the [FeII(PBO)2(CF3SO3)2] (1), [FeII(PBT)2(CF3SO3)2] (2), and [FeII(PBI)3](CF3SO3)2 (3)-catalyzed (PBO = 2-(2'-pyridyl)benzoxazole, PBT = 2-(2'-pyridyl)benzthiazole, PBI = 2-(2'-pyridyl)benzimidazole) Baeyer-Villiger oxidation of cycloketones by dioxygen with cooxidation of aldehydes and peroxycarboxylic acids, including the kinetics on the reactivity of (µ-1,2-peroxo)diiron(III), acylperoxo- and iodosylbenzene-iron(III) species as key intermediates.

Disproportionation of H2O2 Mediated by Diiron-Peroxo Complexes as Catalase Mimics.

Heme iron and nonheme dimanganese catalases protect biological systems against oxidative damage caused by hydrogen peroxide. Rubrerythrins are ferritine-like nonheme diiron proteins, which are structurally and mechanistically distinct from the heme-type catalase but similar to a dimanganese KatB enzyme. In order to gain more insight into the mechanism of this curious enzyme reaction, non-heme structural and functional models were carried out by the use of mononuclear [FeII(L1-4)(solvent)3](ClO4)2 (1-4) (L1 = 1,3-bis(2-pyridyl-imino)isoindoline, L2 = 1,3-bis(4'-methyl-2-pyridyl-imino)isoindoline, L3 = 1,3-bis(4'-Chloro-2-pyridyl-imino)isoindoline, L4 = 1,3-bis(5'-chloro-2-pyridyl-imino)isoindoline) complexes as catalysts, where the possible reactive intermediates, diiron-perroxo [FeIII2(µ-O)(µ-1,2-O2)(L1-L4)2(Solv)2]2+ (5-8) complexes are known and well-characterized. All the complexes displayed catalase-like activity, which provided clear evidence for the formation of diiron-peroxo species during the catalytic cycle. We also found that the fine-tuning of iron redox states is a critical issue, both the formation rate and the reactivity of the diiron-peroxo species showed linear correlation with the FeIII/FeII redox potentials. Their stability and reactivity towards H2O2 was also investigated and based on kinetic and mechanistic studies a plausible mechanism, including a rate-determining hydrogen atom transfer between the H2O2 and diiron-peroxo species, was proposed. The present results provide one of the first examples of a nonheme diiron-peroxo complex, which shows a catalase-like reaction.

Comparison of Nonheme Manganese- and Iron-Containing Flavone Synthase Mimics.

Heme and nonheme-type flavone synthase enzymes, FS I and FS II are responsible for the synthesis of flavones, which play an important role in various biological processes, and have a wide range of biomedicinal properties including antitumor, antimalarial, and antioxidant activities. To get more insight into the mechanism of this curious enzyme reaction, nonheme structural and functional models were carried out by the use of mononuclear iron, [FeII(CDA-BPA*)]2+ (6) [CDA-BPA = N,N,N',N'-tetrakis-(2-pyridylmethyl)-cyclohexanediamine], [FeII(CDA-BQA*)]2+ (5) [CDA-BQA = N,N,N',N'-tetrakis-(2-quinolilmethyl)-cyclohexanediamine], [FeII(Bn-TPEN)(CH3CN)]2+ (3) [Bn-TPEN = N-benzyl-N,N',N'-tris(2-pyridylmethyl)-1,2-diaminoethane], [FeIV(O)(Bn-TPEN)]2+ (9), and manganese, [MnII(N4Py*)(CH3CN)]2+ (2) [N4Py* = N,N-bis(2-pyridylmethyl)-1,2-di(2-pyridyl)ethylamine)], [MnII(Bn-TPEN)(CH3CN)]2+ (4) complexes as catalysts, where the possible reactive intermediates, high-valent FeIV(O) and MnIV(O) are known and well characterised. The results of the catalytic and stoichiometric reactions showed that the ligand framework and the nature of the metal cofactor significantly influenced the reactivity of the catalyst and its intermediate. Comparing the reactions of [FeIV(O)(Bn-TPEN)]2+ (9) and [MnIV(O)(Bn-TPEN)]2+ (10) towards flavanone under the same conditions, a 3.5-fold difference in reaction rate was observed in favor of iron, and this value is three orders of magnitude higher than was observed for the previously published [FeIV(O)(N2Py2Q*)]2+ [N,N-bis(2-quinolylmethyl)-1,2-di(2-pyridyl)ethylamine] species.

Catalytic and stoichiometric flavanone oxidation mediated by nonheme oxoiron(iv) complexes as flavone synthase mimics: kinetic, mechanistic and computational studies.

The present study describes the first example of the stoichiometric and catalytic oxidation of flavanone by synthetic nonheme oxoiron(iv) complexes and their precursor iron(ii) complexes with m-CPBA as the terminal oxidant. These models, including detailed kinetic, mechanistic and computational studies, may serve as the biomimics of flavone synthase (FS) enzymes.

Steric control and the mechanism of benzaldehyde oxidation by polypyridyl oxoiron(iv) complexes: aromatic versus benzylic hydroxylation of aromatic aldehydes.

The present study describes the first example of the hydroxylation of benzaldehydes by synthetic nonheme oxoiron(iv) complexes, where the reactivity, chemoselectivity, and mechanism were strongly influenced by the ligand environment of the iron center.

Formation, Characterization, and Reactivity of a Nonheme Oxoiron(IV) Complex Derived from the Chiral Pentadentate Ligand asN4Py.

The chiral pentadentate low-spin (S = 1) oxoiron(IV) complex [FeIV(O)(asN4Py)]2+ (2) was synthesized and spectroscopically characterized. Its formation kinetics, reactivity, and (enantio)selectivity in an oxygen-atom-transfer reaction was investigated in detail and compared to a similar pentadentate ligand-containing system.