Iron Nitrosyl Complexes Research Articles

How is Nitric Oxide (NO) Converted into Nitrosonium Cations (NO+) in Living Organisms? (Based on the Results of Optical and EPR Analyses of Dinitrosyl Iron Complexes with Thiol-Containing Ligands).

The present work provides theoretical and experimental foundations for the ability of dinitrosyl iron complexes (DNICs) with thiol-containing ligands to be not only the donors of neutral NO molecules, but also the donors of nitrosonium cations (NO+) in living organisms ensuring S-nitrosation of various proteins and low-molecular-weight compounds. It is proposed that the emergence of those cations in DNICs is related to disproportionation reaction of NO molecules, initiated by their binding with Fe2+ ions (two NO molecules per one ion). At the same time, possible hydrolysis of iron-bound nitrosonium cations is prevented by the electron density transition to nitrosonium cations from sulfur atoms of thiol-containing ligands, which are included in the coordination sphere of iron. It allows supposing that iron in iron–nitrosyl complexes of DNICs has a d7 electronic configuration. This supposition is underpinned by experimental data revealing that a half of nitrosyl ligands are converted into S-nitrosothiols (RSNOs) when those complexes decompose, with the other half of those ligands released in the form of neutral NO molecules.

Exploring the Limits of Dative Boratrane Bonding: Iron as a Strong Lewis Base in Low-Valent Non-Heme Iron-Nitrosyl Complexes.

We previously reported the synthesis and preliminary characterization of a unique series of low-spin (ls) {FeNO}8-10 complexes supported by an ambiphilic trisphosphineborane ligand, [Fe(TPB)(NO)]+/0/-. Herein, we use advanced spectroscopic techniques and density functional theory (DFT) calculations to extract detailed information as to how the bonding changes across the redox series. We find that, in spite of the highly reduced nature of these complexes, they feature an NO+ ligand throughout with strong Fe-NO π-backbonding and essentially closed-shell electronic structures of their FeNO units. This is enabled by an Fe-B interaction that is present throughout the series. In particular, the most reduced [Fe(TPB)(NO)]- complex, an example of a ls-{FeNO}10 species, features a true reverse dative Fe → B bond where the Fe center acts as a strong Lewis-base. Hence, this complex is in fact electronically similar to the ls-{FeNO}8 system, with two additional electrons "stored" on site in an Fe-B single bond. The outlier in this series is the ls-{FeNO}9 complex, due to spin polarization (quantified by pulse EPR spectroscopy), which weakens the Fe-NO bond. These data are further contextualized by comparison with a related N2 complex, [Fe(TPB)(N2)]-, which is a key intermediate in Fe(TPB)-catalyzed N2 fixation. Our present study finds that the Fe → B interaction is key for storing the electrons needed to achieve a highly reduced state in these systems, and highlights the pitfalls associated with using geometric parameters to try to evaluate reverse dative interactions, a finding with broader implications to the study of transition metal complexes with boratrane and related ligands.

The Ability of Blood Plasma to Inhibit Catalase in the Presence of Chloride is a Highly Sensitive Indicator of Deposited Nitric Oxide and Leukocyte Activation

Aims: To find out the origin of so-called nitrite - like substance (NLS) that appears in the blood plasma in patients with inflammatory diseases and the mechanism of its occurrence. To justify the possibility of registering its appearance in the blood as a highly sensitive indicator of leukocyte activation. Background: The need for a simple, sensitive and specific method of early diagnosis of inflammation, the key stage of which is the activation of white blood cells. Objective: To find out the origin of so-called nitrite - like substance (NLS) that appears in the blood plasma in patients with inflammatory diseases before the onset of clinical signs. This substance is able to inhibit catalase in the presence of chloride which is typical for nitrite and nitrosoamines. Methods: The catalase activity was determined by the calorimetric method based on the control of the kinetics of heat production accompanying hydrogen peroxide decomposition. Results: Blood plasma contains deposited nitric oxide included in various nitrosyl iron complexes. These complexes effectively interact with the superoxide produced by activated leukocytes. This interaction produces a number of substances that have the ability to inhibit catalase in the presence of chloride. These substances retain the ability to inhibit in the system: hemoglobin-iron chelator, or hemoglobin-mercury salt. Such properties are characteristic of nitrite and nitrosoamines. Normally, these substances are present in plasma in trace amounts. 700 activated cells per microliter (10 times less than normal in human blood) are enough to transform about 30% nitrosyl iron complexes contained in plasma into NLS. Conclusion: The appearance of NLS is a very sensitive indicator of leukocyte activation.

A divergent mode of activation of a nitrosyl iron complex with unusual antiangiogenic activity

Nitric oxide (NO) and nitroxyl (HNO) have gained broad attention due to their roles in several physiological and pathophysiological processes. Remarkably, these sibling species can exhibit opposing effects including the promotion of angiogenic activity by NO compared to HNO, which blocks neovascularization. While many NO donors have been developed over the years, interest in HNO has led to the recent emergence of new donors. However, in both cases there is an expressive lack of iron-based compounds. Herein, we explored the novel chemical reactivity and stability of the trans-[Fe(cyclam)(NO)Cl]Cl2 (cyclam = 1,4,8,11-tetraazacyclotetradecane) complex. Interestingly, the half-life (t1/2) for NO release was 1.8 min upon light irradiation, vs 5.4 h upon thermal activation at 37 °C. Importantly, spectroscopic evidence supported the generation of HNO rather than NO induced by glutathione. Moreover, we observed significant inhibition of NO donor- or hypoxia-induced HIF-1α (hypoxia-inducible factor 1α) accumulation in breast cancer cells, as well as reduced vascular tube formation by endothelial cells pretreated with the trans-[Fe(cyclam)(NO)Cl]Cl2 complex. Together, these studies provide the first example of an iron-nitrosyl complex with anti-angiogenic activity as well as the potential dual activity of this compound as a NO/HNO releasing agent, which warrants further pharmacological investigation.

Nitric oxide metabolism in the human placenta during aberrant maternal inflammation.

Nitric oxide (NO) is a gasotransmitter with important physiological and pathophysiological roles in pregnancy. There is limited information available about the sources and metabolism of NO and its bioactive metabolites (NOx) in both normal and complicated pregnancies. The present study characterized and quantified endogenous NOx in human and mouse placenta following determination of the stability of exogenous NOx in placental homogenates. NOx have differential stability in placental homogenates. NO and iron nitrosyl species (FeNOs), are relatively unstable in placental homogenates from normal placentas. Exogenous NO, nitrite and nitrosothiols react with placental homogenates to form iron nitrosyl complexes. FeNOs were also detected endogenously in mouse and human placenta. NOx levels in placental villous tissue are increased in fetal growth restriction vs. placentas from women with normal pregnancies, particularly in fetal growth restriction associated with pre-eclampsia. Villitis was not associated, however, with an increase in NOx levels in either normotensive or pre-eclamptic placentas. The results call for further investigation of FeNOs in normal and complicated pregnancies. Nitric oxide (NO) is a gasotransmitter with important roles in pregnancy under both physiological and pathophysiological conditions. Although products of NO metabolism (NOx) also have significant bioactivity, little is known about the role of NO and NOx under conditions of aberrant placental inflammation during pregnancy. An ozone-based chemiluminescence approach was used to investigate the stability and metabolic fate of NOx in human placental homogenates from uncomplicated pregnancies in healthy mothers compared to that in placental tissue from normotensive and pre-eclamptic pregnancies complicated with fetal growth restriction (FGR) with and without villitis of unknown aetiology. We hypothesized that placental NOx would be increased in FGR vs. normal tissue, and be further increased in villitis vs. non-villitis placentas. Findings indicate that nitrate, nitrite and nitrosothiols, but not NO or iron nitrosyl species (FeNOs), are relatively stable in placental homogenates from normal placentas, and that NO, nitrite and nitrosothiols react with placental homogenates to form iron nitrosyl complexes. Furthermore, NOx levels in placental villous tissue are increased in FGR vs. placentas from women with normal pregnancies, particularly in FGR associated with pre-eclampsia. However, in contrast to our hypothesis, villitis was not associated with an increase in NOx levels in either normotensive or pre-eclamptic placentas. Our results also strongly support the involvement of FeNOs in both mouse and human placenta, and call for their further study as a critical mechanistic link between pre-eclampsia and fetal growth restriction.

Synthesis and Metabolism of Nitric Oxide (NO) in Chicken Embryos and in the Blood of Adult Chicken.

In chicken embryos, nitric oxide (NO) is accumulated in the pool of NO donors: S-nitrosothiols, nitrosyl-iron complexes, high-molecular-weight nitro-compounds. Oxidation of NO to nitrate occurs with different intensity in the embryos of different chicken breeds. In some embryos, NO donors accumulate almost without oxidation. Stable concentration of NO donors and nitrate in the blood of adult chicken is a result of dynamic equilibrium between NO synthesis and elimination (oxidation, consumption by other tissues, and excretion). As NO oxidation occurs mainly not in the blood, but in other tissues, decomposition of NO donors and NO oxidation are determined the properties of these tissues, in particular, the presence of physiological targets of NO, rather than spontaneous processes. Hence, evaluation of the intensity of NO metabolism is important for prediction of the efficiency of preparations containing NO donors and stimulators of its synthesis.

Identification of the Products of the Reaction of Nitrosyl Iron Complexes with Phosphoenolpyruvic Acid by Mass Spectrometry

The reaction of the tetranitrosyl iron complex containing the thiosulfate ligand (TNIC) (NO donor) with phosphoenolpyruvic acid (PEP), which is one of the main biological macroergic compounds, was studied by mass spectrometry. The use of mass spectrometry made it possible to perform studies in an aqueous medium, separate the substances, and quantitatively correlate the peak intensities with the concentrations of the substances. The products of the reaction of PEP with TNIC were identified by IR spectroscopy and mass spectrometry. The reaction product was found to have a Fe–O–C bond. Among the reaction products, the ions with m/z = 318 and 256 belong to the compounds [O3S2–Fe–PEP]–2, and [S-Fe–PEP]–2, respectively.

Decomposition of the binuclear nitrosyl iron complex with thiosulfato ligands in aqueous solutions: Experimental and theoretical study

In this work, transformations of the anionic binuclear tetranitrosyl iron complex with thiosulfato ligands (Na2[Fe2(S2O3)2(NO)4]·4H2O) (1) have been studied in aqueous anaerobic and aerobic solutions. Under anaerobic conditions, complex 1 was shown to undergo intramolecular isomerization, in addition to NO generation, due to embedding of the oxygen atom of the thiosulfato ligand in the Fe-S bonds. The complex becomes more stable, so its further transformation, including NO release, is unlikely. The model for the complex decomposition has been suggested, and reaction rate constants have been calculated using the kinetic modeling method.As follows from the experimental data, under aerobic conditions, complex 1 is oxidized and becomes a more effective NO donor. Due to the incorporation of the oxygen atom into the Fe-S bonds, mononuclear nitrosyl intermediates are formed, which have a typical EPR signal (g = 2.03).

Synthesis, properties, and antibacterial activity of a new nitric oxide donor — a nitrosyl iron complex with 5-phenyl-1H-1,2,4-triazole-3-thiol

A new binuclear μ-NSC-type nitrosyl iron complex [Fe2(SR)2(NO)4] (R is 5-phenyl-1H-1,2,4-triazole-3-thiolyl) was synthesized. The composition and structure of the newly synthesized complex were determined by atomic absorption, IR, EPR, and Mossbauer spectroscopy and SQUID magnetometry. Amperometric analysis showed that the new complex is an effective nitric oxide (NO) donor in a 1% aqueous DMSO solution. The amounts of NO generated by the complex [Fe2(SR)2(NO)4] in aqueous solutions at physiological pH values were determined. The new complex was shown to have higher antibacterial activity against the gram-positive bacteria Micrococcus luteus compared to kanamycin and streptomycin. According to assays, sulfur-containing ligands of the 1,2,4-triazole-3-thiol series are promising for the design of new antibacterial agents containing the {Fe(NO)2} structural moiety.

The Fe2(NO)2 Diamond Core: A Unique Structural Motif In Non‐Heme Iron–NO Chemistry

AbstractNon‐heme high‐spin (hs) {FeNO}8 complexes have been proposed as important intermediates towards N2O formation in flavodiiron NO reductases (FNORs). Many hs‐{FeNO}8 complexes disproportionate by forming dinitrosyl iron complexes (DNICs), but the mechanism of this reaction is not understood. While investigating this process, we isolated a new type of non‐heme iron nitrosyl complex that is stabilized by an unexpected spin‐state change. Upon reduction of the hs‐{FeNO}7 complex, [Fe(TPA)(NO)(OTf)](OTf) (1), the N‐O stretching band vanishes, but no sign of DNIC or N2O formation is observed. Instead, the dimer, [Fe2(TPA)2(NO)2](OTf)2 (2) could be isolated and structurally characterized. We propose that 2 is formed from dimerization of the hs‐{FeNO}8 intermediate, followed by a spin state change of the iron centers to low‐spin (ls), and speculate that 2 models intermediates in hs‐{FeNO}8 complexes that precede the disproportionation reaction.

Conversion of a Fleeting Open‐Shell Iron Nitride into an Iron Nitrosyl

Terminal metal nitrides have been proposed as key intermediates in a series of pivotal chemical transformations. However, exploring the chemical activity of transient tetragonal iron(V) nitrides is largely impeded by their facile dimerization in fluid solutions. Herein, in situ EPR and Mössbauer investigations are presented of unprecedented oxygenation of a paramagnetic iron(V) nitrido intermediate, [FeVN(cyclam‐ac)]+ (2, cyclam‐ac−=1,4,8,11‐tetraazacyclotetradecane‐1‐acetate anion), yielding an iron nitrosyl complex, [Fe(NO)(cyclam‐ac)]+ (3). Further theoretical studies suggest that during the reaction a closed‐shell singlet O atom is transferred to 2. Consequently, the N−O bond formation does not follow a radical coupling mechanism proposed for the N−N bond formation but is accomplished by three mutual electron‐transfer pathways between 2 and the O atom donor, thanks to the ambiphilic nature of 2.

Conversion of a Fleeting Open‐Shell Iron Nitride into an Iron Nitrosyl

AbstractTerminal metal nitrides have been proposed as key intermediates in a series of pivotal chemical transformations. However, exploring the chemical activity of transient tetragonal iron(V) nitrides is largely impeded by their facile dimerization in fluid solutions. Herein, in situ EPR and Mössbauer investigations are presented of unprecedented oxygenation of a paramagnetic iron(V) nitrido intermediate, [FeVN(cyclam‐ac)]+ (2, cyclam‐ac−=1,4,8,11‐tetraazacyclotetradecane‐1‐acetate anion), yielding an iron nitrosyl complex, [Fe(NO)(cyclam‐ac)]+ (3). Further theoretical studies suggest that during the reaction a closed‐shell singlet O atom is transferred to 2. Consequently, the N−O bond formation does not follow a radical coupling mechanism proposed for the N−N bond formation but is accomplished by three mutual electron‐transfer pathways between 2 and the O atom donor, thanks to the ambiphilic nature of 2.

Antioxidant activity of tetra nitrosyl iron complex with thiosulfate ligands and its effect on catalytic activity of mitochondrial enzymes in vitro

The antioxidant and antiradical properties of the tetra nitrosyl iron complex with thiosulfate ligands (TNIC) in the mouse brain homogenates in vitro were also studied. It was found for the first time that TNIC is an effective antioxidant. The effect of TNIC on the catalytic activity of mitochondrial enzymes: cytochrome c oxidase and monoamine oxidase A has been studied. It was shown for the first time that TNIC is an inhibitor of the catalytic activity of cytochrome c oxidase and monoamine oxidase A in the brain mitochondria isolated from animals in vitro.

Super-quantum discord in ferromagnetic and antiferromagnetic materials

Super-quantum discord is an extension of the quantum discord concept where weak measurements are made instead of projective measurements. We study the temperature behavior of the super-quantum discord for two real magnetic materials. We extract information about super-quantum discord from the magnetic susceptibility data for iron nitrosyl complexes $\mathrm{ Fe_2(SC_3 H_5N_2)_2(NO)_4}$ and binuclear Cu(II) acetate complex $\mathrm{[Cu_2 L(OAc)]\cdot 6 H_2O}$, where $\mathrm{ L}$ is a ligand that allows us to compare the super-quantum discord with the standard one. The dependence of the super-quantum discord on the parameter describing weak measurements is studied. Obtained difference between super-quantum and quantum discords confirms the detection of additional quantum correlations that are usually destroyed during projective measurements. The use of the approach allows to predict quantitatively in advance the advantages of use of weak measurements versus projective one for quantum technologies in real settings where quantum discord is used as resource. This can be relevant particularly in macroscopic quantum systems where weak measurements can be used to extract information about the system.

A Series of Iron Nitrosyl Complexes {Fe-NO}6-9 and a Fleeting {Fe-NO}10 Intermediate en Route to a Metalacyclic Iron Nitrosoalkane.

Iron-nitrosyls have fascinated chemists for a long time due to the noninnocent nature of the NO ligand that can exist in up to five different oxidation and spin states. Coordination to an open-shell iron center leads to complex electronic structures, which is the reason Enemark-Feltham introduced the {Fe-NO}n notation. In this work, we succeeded in characterizing a series of {Fe-NO}6-9 complexes, including a reactive {Fe-NO}10 intermediate. All complexes were synthesized with the tris-N-heterocyclic carbene ligand tris[2-(3-mesitylimidazol-2-ylidene)ethyl]amine (TIMENMes), which is known to support iron in high and low oxidation states. Reaction of NOBF4 with [(TIMENMes)Fe]2+ resulted in formation of the {Fe-NO}6 compound [(TIMENMes)Fe(NO)(CH3CN)](BF4)3 (1). Stepwise chemical reduction with Zn, Mg, and Na/Hg leads to the isostructural series of high-spin iron nitrosyl complexes {Fe-NO}7,8,9 (2-4). Reduction of {Fe-NO}9 with Cs electride finally yields the highly reduced {Fe-NO}10 intermediate, key to formation of [Cs(crypt-222)][(TIMENMes)Fe(NO)], (5) featuring a metalacyclic [Fe-(NO-NHC)3-] nitrosoalkane unit. All complexes were characterized by single-crystal XRD analyses, temperature and field-dependent SQUID magnetization methods, as well as 57Fe Mössbauer, IR, UV/vis, multinuclear NMR, and dual-mode EPR spectroscopy. Spectroscopy-based DFT analyses provide insight into the electronic structures of all compounds and allowed assignments of oxidation states to iron and NO ligands. An alternative synthesis to the {Fe-NO}8 complex was found via oxygenation of the nitride complex [(TIMENMes)Fe(N)](BF4). Surprisingly, the resulting {Fe-NO}8 species is electronically and structural similar to the [(TIMENMes)Fe(N)]+ precursor. Based on the structural and electronic similarities between this nitrosyl/nitride complex couple, we adopted the strategy, developed by Wieghardt et al., of extending the Enemark-Feltham nomenclature to nitrido complexes, rendering [(TIMENMes)Fe(N)]+ as a {Fe-N}8 species.

Activation of Non-Heme Iron-Nitrosyl Complexes: Turning Up the Heat

The chemistry of nonheme iron centers with NO in different oxidation states has experienced a renaissance in the last 10 years because of recent findings of their involvement in N2O generation (in ...

Antioxidant Activity of Tetranitrosyl Iron Complex with Thiosulfate Ligands and Its Effect on Catalytic Activity of Mitochondrial Enzymes In vitro.

The antioxidant and antiradical properties of the tetra nitrosyl iron complex with thiosulfate ligands (TNIC) were studied in vitro in mouse brain homogenates. It was found for the first time that TNIC is an effective antioxidant. The effect of TNIC on the catalytic activity of mitochondrial enzymes cytochrome c oxidase and monoamine oxidase A was studied. It was shown for the first time that TNIC is an inhibitor of the catalytic activity of cytochrome c oxidase and monoamine oxidase A in animal brain mitochondria in vitro.

Conformational effect of thiol-compounds on the formation of a nitrosyl(protoporphyrinato)iron(II) complex adsorbed on a basic oxide of magnesium oxide powder with the nitrite ion

Conformational effect of thiol-compounds on the formation of a nitrosyl(protoporphyrinato)iron(II) complex adsorbed on a basic oxide of magnesium oxide powder with the nitrite ion

Redox reactions of cationic nitrosyl iron complexes with thiourea and its aliphatic derivatives: The experiment and DFT investigation

Redox reactions of cationic nitrosyl iron complexes with thiourea and its aliphatic derivatives have been studied using cyclic voltammetry technique and DFT investigation. Experimental values of the redox potentials have been determined and compared with results of DFT calculations. Using quantum-chemical modeling, structures of the forming reduced and oxidized forms have been obtained and their electronic structures have been studied. The redox processes in these systems were shown to be complicated and accompanied by the complexes decomposition. It is very important for understanding of their reactivity.

NO-Donor Nitrosyl Iron Complex with 2-Aminophenolyl Ligand Induces Apoptosis and Inhibits NF-κB Function in HeLa Cells.

NO donating iron nitrosyl complex with 2-aminothiophenyl ligand (2-AmPh complex) was studied for its ability to cause cell death and affect nuclear factor kappa B (NF-κB) signaling. The complex inhibited viability of HeLa cells and induced cell death that was accompanied by loss of mitochondrial membrane potential and characteristic for apoptosis phosphatidylserine externalization. At IC50, 2-AmPh caused decrease in nuclear content of NF-κB p65 polypeptide and mRNA expression of NF-κB target genes encoding interleukin-8 and anti-apoptotic protein BIRC3. mRNA levels of interleukin-6 and anti-apoptotic protein BIRC2 encoding genes were not affected. Our data demonstrate that NO donating iron nitrosyl complex 2-AmPh can inhibit tumor cell viability and induce apoptosis that is preceded by impairment of NF-κB function and suppression of a subset of NF-κB target genes.