Formation Of Iron Complexes Research Articles

Mechanisms of the Formation and Function of Dinitrosyl Iron Complexes as a “Working Form” of Nitric Oxide in Living Organisms

It has been proposed that only the introduction of endogenous nitric oxide (NO) into dinitrosyl iron complexes (DNIC) or S-nitrosothiols (RS-NO) can ensure stabilization of NO that is critical for operating in an auto/paracrine manner as a regulator of biological processes in living organisms. Without this introduction, the majority of endogenous NO disappears due to aggressive intra/intercellular environment thereby eliminating it from metabolic processes. Administration of exogenous NO in human and animal organisms (the only possible route of administration is via inhalation when it is in the gaseous state) does not lead to formation of DNIC or RS-NO in blood or other tissues. Hence, the majority of exogenous NO during its inhalation is converted into nitrosonium cations (NO+), the emergence of which is evidenced by their conversion into RS-NO when various thiol-containing compounds are administered to animal blood concomitantly. In turn, RS-NO formation in those animals was manifested by hypotensive effect on them. NO molecule transformation into nitrosonium cations may also occur during DNIC formation induced by a disproportionation reaction of endogenous NO molecules binding with Fe2+ ions in pairs. Subsequent binding of Fe(NO)2 groups to thiol-containing ligands that occur during this reaction promotes formation of rather stable DNICs that act as donors of both neutral molecules of NO and nitrosonium cations (NO+) in living organisms. The transfer of NO and NO+ to targets for nitrosation reactions occurs by the interaction of low molecular DNICs with heme groups of heme-containing proteins (for example, guanylate cyclase) or thiol groups in low molecular or protein thiol-containing compounds. This paper presents different results of NO and NO+ transfer in living organisms disussing both positive, regulatory and negative, toxic effects of it.

A Crucial Role of Proteolysis in the Formation of Intracellular Dinitrosyl Iron Complexes.

Dinitrosyl iron complexes (DNICs) stabilize nitric oxide in cells and tissues and constitute an important form of its storage and transportation. DNICs may comprise low-molecular-weight ligands, e.g., thiols, imidazole groups in chemical compounds with low molecular weight (LMWDNICs), or high-molecular-weight ligands, e.g., peptides or proteins (HMWDNICs). The aim of this study was to investigate the role of low- and high-molecular-weight ligands in DNIC formation. Lysosomal and proteasomal proteolysis was inhibited by specific inhibitors. Experiments were conducted on human erythroid K562 cells and on K562 cells overexpressing a heavy chain of ferritin. Cell cultures were treated with •NO donor. DNIC formation was monitored by electron paramagnetic resonance. Pretreatment of cells with proteolysis inhibitors diminished the intensity and changed the shape of the DNIC-specific EPR signal in a treatment time-dependent manner. The level of DNIC formation was significantly influenced by the presence of protein degradation products. Interestingly, formation of HMWDNICs depended on the availability of LMWDNICs. The extent of glutathione involvement in the in vivo formation of DNICs is minor yet noticeable, aligning with our prior research findings.

COMPLEXATION OF IRON(III) WITH TSC AND FTSC IN H2SO4 SOLUTIONS OF VARIABLE COMPOSITION

The process of complex formation of iron (III) with thiosemicarbazide and 1-formyl-3-thiosemicarbazide in H2SO4 solutions of various concentrations was studied using the potentiometric method. The stability constants of the resulting complexes were calculated, and the ionization constants of the ligands were estimated under the same conditions. It was shown that the stepwise nature of complex formation does not depend on the concentration of hydrogen ions. However, the stability of the complexes decreases with increasing pH. A study of the complex formation of iron(III) with thiosemicarbazide and its acyl derivative showed that there are both similarities and differences in the nature of complex formation. Both ligands react with iron(III) in a stepwise manner, forming stable complexes. With increasing temperature, the stability of the complexes increases. Changing the ionic strength of the solution and the concentration of H2SO4 equally affect the stability of the complexes. At the same time, moving from thiosemicarbazide to 1-formyl-3-thiosemicarbazide, the number of particles formed in the solution decreases, and the stability of the complexes decreases.

Insight into the relevance of dinitrosyl iron complex (DNIC) formation in the absence of thiols in aqueous media.

DNIC can be formed in aqueous media in the absence of thiols via mechanisms that depend exclusively on Fe(II) and NO. However, these reactions do not take place at intracellular concentrations of Fe(II) and NO, reinforcing the relevance of thiols to assist Fe(II) to Fe(I) reduction during DNIC formation in biological media.

Wound Healing Improvement by Polymer Surgical Suture Coated with Tannic Acid

A surgical suture is a vital medical device to uphold wounded tissue during surgery. However, the application to improve tissue healing must still be developed. This study offered to solve this problem by incorporating tannic acid (TA) into polydioxanone (PDS) sutures. The PDS suture was immersed in TA complexing with iron (III) solutions in pH 8.0 solution. The engineered suture was successful, as revealed by the OH peak of TA in FTIR spectra. Furthermore, it was confirmed by TA particle appearance under Scanning Electron Microscopy. Contact angle measurement showed better wettability in biological mimicking solutions, such as water, serum, and saline solution. Thereby, it improved in vitro wound healing activity. Moreover, our bioinformatics data showed that TA enhanced the wound healing process by addressing multiple targets in the early phase of inflammation. For instance, it induced platelets to reduce bleeding at the early wound healing stage, activated T cells at the inflammation stage, accelerated epidermis cell proliferation, and activated fibroblast as a key player in wound healing. Due to multiple wound healing targets, our suture system was expected to be emphasized in clinical applications. HIGHLIGHTS The engineered surgical suture was fabricated by modifying the surface of surgical suture with tannic acid (TA) through iron (III) complex formation in basic condition The modified PDS suture had a high wettability degree of water, saline, and serum, representing the biological fluid, which was expected to have better biocompatibility Based on bioinformatics analysis, TA revealed multiple targets to stop bleeding by activating platelet through FYN, CD4, and CD8 T cells, induced epithelial cells proliferation through Epidermal Growth Factor Receptor (EGFR), and activated many transcription and migration factors of fibroblast GRAPHICAL ABSTRACT

Thermodynamic Characteristics of the Formation of Iron(II) and Iron(III) Complexes with L-Alanine in Aqueous Solutions

Thermodynamic Characteristics of the Formation of Iron(II) and Iron(III) Complexes with L-Alanine in Aqueous Solutions

Bacterial nitric oxide reductase (NorBC) models employing click chemistry

Bacterial NO Reductase (NorBC or cNOR) is a membrane-bound enzyme found in denitrifying bacteria that catalyzes the two-electron reduction of NO to N2O and water. The mechanism by which NorBC operates is highly debated, due to the fact that this enzyme is difficult to work with, and no intermediates of the NO reduction reaction could have been identified so far. The unique active site of NorBC consists of a heme b3/non-heme FeB diiron center. Synthetic model complexes provide the opportunity to obtain insight into possible mechanistic alternatives for this enzyme. In this paper, we present three new synthetic model systems for NorBC, consisting of a tetraphenylporphyrin-derivative clicked to modified BMPA-based ligands (BMPA = bis(methylpyridyl)amine) that model the non-heme site in the enzyme. These complexes have been characterized by EPR, IR and UV–Vis spectroscopy. The reactivity with NO was then investigated, and it was found that the complex with the BMPA-carboxylate ligand as the non-heme component has a very low affinity for NO at the non-heme iron site. If the carboxylate functional group is replaced with a phenolate or pyridine group, reactivity is restored and formation of a diiron dinitrosyl complex was observed. Upon one-electron reduction of the nitrosylated complexes, following the semireduced pathway for NO reduction, formation of dinitrosyl iron complexes (DNICs) was observed in all three cases, but no N2O could be detected.

Polymeric smart coatings containing modified capped halloysite nanotubes for corrosion protection of carbon steel

A newly designed smart self-healing epoxy coating system comprised of modified halloysite nanotubes (HNTs) having capping is proposed for corrosion protection of steel. In the first step, HNTs were loaded with 8-hydroxyquinoline (8HQ), used as a corrosion inhibitor. Then the HNTs were sealed/capped using cobalt (II), aiming for an efficient and controlled release of the loaded inhibitor. The smart coatings were developed by reinforcing loaded HNTs into the epoxy matrix. The structural, thermal, mechanical, and electrochemical properties of capped modified HNTs and smart coatings were studied using various techniques. UV–Vis analysis depicted that the capping of the metal-inhibitor complex was decomposed at acidic pH resulting in a controlled release of the loaded inhibitor into HNTs. Electrochemical impedance spectroscopic (EIS) analysis of blank and smart coatings demonstrated that the low-frequency impedance modulus of smart coatings is 109 Ω.cm2 for 20 days compared to blank coatings (105 Ω.cm2), reflecting their excellent corrosion inhibition performance. The superior corrosion protection properties of these smart coatings can be ascribed to the controlled and efficient release of the loaded inhibitor from the capped HNTs. Finally, X-ray photoelectron spectroscopy (XPS) analysis of the steel substrate after the corrosion analysis revealed the adsorption of 8HQ on the steel surface, confirming the formation of iron complex due to the release of loaded inhibitor. This work demonstrated the adeptness of 8HQ in mitigating the corrosion due to the controlled and effective release of the inhibitor from capped HNTs because of dissociation of the metal-inhibitor complex (Co-8HQ).Graphical abstract

Molecular mechanism of the unusual biphasic effects of the natural compound hinokitiol on iron-induced cellular DNA damage.

Hinokitiol is a natural monoterpene compound found in the heartwood of cupressaceous plants that have anticancer and anti-inflammatory properties. However, few studies have focused on its effect on iron-mediated cellular DNA damage. Here we show that hinokitiol exhibited unusual biphasic effects on iron-induced DNA damage in a molar ratio (hinokitiol/iron) dependent manner in HeLa cells. Under low ratios (<3:1), hinokitiol markedly enhanced DNA damage induced by Fe(II) or Fe(II)-H2O2; However, when the ratios increased over 3:1, the DNA damage was progressively inhibited. We found that the total cytoplasmic and nuclear iron concentration increased as the ratios of hinokitiol/iron increased. However, the cellular level of labile iron pool (LIP) only increased at ratios lower than 3, and the ROS generation is consistent with LIP change. Hinokitiol was found to interact with iron to form lipophilic hinokitiol-iron complexes with different stoichiometry and redox-activity by complementary applications of various analytical methods. Taken together, we propose that the enhancement of iron-induced cellular DNA damage by hinokitiol at low ratios (<3:1) was due to formation of lipophilic and redox-active iron complexes which facilitated cellular iron uptake and •OH production, while the inhibition at ratios higher than 3 was due to formation of redox-inactive iron complexes. These new findings will help us to design more effective drugs for the prevention and treatment of a series of iron-related diseases via regulating the two critical physicochemical factors (lipophilicity and redox activity of iron complexes) by simple natural compounds with iron-chelating properties.

Determination of iron (III) in environmental objects by photometric method with acetylacetone derivatives

Organic reagents containing three carbonyl groups based on acetylacetone, 2,4-diacetyl-3-phenyl-5-methyl-5-hydroxyhexanone (R1), 2,4-diacetyl-3-(3'-nitrophenyl)-5-hydroxy-5-methylcyclohexanone (R2) and 3-acetyl-4,6-diphenylgensandione-2,6 (R3), were synthesized. Their absorption spectra were studied at various pH values of the medium, and the acidity constants were determined by potentiometric titration. It was found that the reagents are monobasic acids and, depending on the acidity of the medium, can be in the molecular (HR) or anionic (R-) form. Formation of iron (III) complexes with synthesized reagents in the presence of hydrophobic amines, 1,10-phenanthroline (Phen), diantipyrylmethane (DAM) and diantipyrylphenylmethane (DAPM) was studied. It was established that mixed ligand complexes with the components ratio of 1:1:1 were formed in the presence of hydrophobic amines. At the same time bathochromic shifts in the absorption spectra were observed and the maximum yield was noted in a more acidic medium compared to the corresponding single ligand complexes. The influence of the reagents concentration, time and temperature on the formation of mixed ligand complexes was studied, and the stability constants were determined by various methods. It was shown that iron (III) in the form of mixed ligand complexes, Fe(III)-R1-DAM, Fe(III)-R2-Phen and Fe(III)-R3-DAM, can be determined with high selectivity in the presence of large excess of other metal cations. The developed methods were tested on fruits – strawberries, apricots, cherries, white cherries and two varieties of apples (Golden Ahmadi and Simirenko), and natural waters – drinking water taken from a tap in the BSU laboratory and Caspian Sea water taken near the Turkan village of Baku city.

High Dose Inhalation with Gaseous Nitric Oxide in COVID-19 Treatment

A method of treatment of a new coronavirus infection COVID-19 in patients undergoing high flow oxygenation is proposed and technically implemented; the method is based on high-dose inhalation of gaseous nitric oxide (NO) with the patient’s spontaneous breathing. The results of the treatment of this disease demonstrating the high efficiency of the new method are presented. A possible mechanism of the blocking effect of high doses of inhaled nitric oxide on the replication of the SARS-CoV-2 virus is discussed; it is based on the formation of dinitrosyl iron complexes in the respiratory tract and lungs of COVID-19 patients with thiol-containing ligands acting as donors of NO and nitrosonium NO+ cations in a living organism that have a cytotoxic effect on the SARS CoV-2 virus.

The influence of non-thiol biomolecules on dinitrosyl iron complex (DNIC) formation

The influence of non-thiol biomolecules on dinitrosyl iron complex (DNIC) formation

Positive (Regulatory) and Negative (Cytotoxic) Effects of Dinitrosyl Iron Complexes on Living Organisms.

The proposed in our studies mechanism of dinitrosyl iron complex (DNIC) formation through the main step of disproportionation of two NO molecules in complex with Fe2+ ion leads to emergence of the resonance structure of dinitrosyl-iron fragment of DNIC, [Fe2+(NO)(NO+)]. The latter allowed suggesting capacity of these complexes to function as donor of both neutral NO molecules as well as nitrosonium cations (NO+), which has been demonstrated in experiments. Analysis of biological activity of DNICs with thiol-containing ligands presented in this review demonstrates that NO molecules and nitrosonium cations released from the complexes exert respectively positive (regulatory) and negative (cytotoxic) effects on living organisms. It has been suggested to use dithiocarbamate derivatives to enhance selective release of nitrosonium cations from DNIC in living organisms followed by simultaneous incorporation of the released NO molecules into the biologically non-active mononitrosyl iron complexes with dithiocarbamate derivatives.

Photochemical assisted novel formation of δ-lactone utilizing trimethylsilylacetylene, isopropanol and ironpentacarbonyl

As evidenced by previous research, photochemical reaction of terminal acetylene and ironpentacarbonyl produces a variety of products with slight changes in reaction conditions. The time of UV-irradiation is one of the most important parameter which decide the selectivity of the product of the reaction. In this report, a novel method for the synthesis of a (tricarbonyl)iron complex of δ-lactone/2-pyranone has been achieved by photochemical reaction of trimethylsilyl acetylene, ironpentacarbonyl and iso-propanol. The pyranone ring was formed by the cyclization of acetylene, iso-propanol and carbonmonoxide. Further, the Fe(CO)3 moiety coordinatively attaches to the π-electron clouds of lactone ring. The successful transformation of 2-pyranone from the (tricarbonyl)iron complex of 2-pyranone was also established by following the demetalation of Fe(CO)3. The formation of (tricarbonyl)iron complex and 2-pyranone were confirmed by various spectroscopic techniques, which includes the 1H, 13C and mass spectrometry. Moreover, the molecular structure of (tricarbonyl)iron complex of δ-lactone or 2-pyranone was established by the single crystal X-ray diffraction analysis.

Localized corrosion behavior studies by SVET of 1010 steel in different concentrations of sodium chloride containing [m-2HEA][Ol] ionic liquid as corrosion inhibitor

The anticorrosive performance and the inhibition mechanism of N-methyl-2-hydroxyethylammonium oleate,[m-2HEA][Ol], in electrolytes with different concentrations of NaCl, was studied using the scanning vibrating electrode technique (SVET), open circuit potential (OCP), polarization curve measurements, complemented by physicochemical analysis by Scanning Electron Microscopy coupled with Energy Dispersive X-ray (SEM-EDS) and Fourier transform infrared spectrometry (FTIR) in attenuated total reflection (ATR). [m-2HEA][Ol] was found to act immediately after immersion due to adsorption on the steel surface competing with chloride ions. SVET and physicochemical analysis revealed the nucleation of metastable pits that were inhibited by the formation of iron complexes with moieties of ionic liquid.

Formation of polynuclear iron(III) complexes of N-(2-pyridylmethyl)iminodipropanol depending on pseudohalide ions: synthesis, crystal structure, and magnetic properties

Five polynuclear iron(III) complexes, [(pmidp)Fe(NCSe)]2 (1), [(pmidp)Fe(NCBH3)]2 (2), [(Hpmidp/pmidp)Fe3(CH3O)2(NCS)4]∙H2O (3), [(pmidp)2Fe6(CH3O)4(N3)4(CH3COO)2O2] (4), and [(pmidp)2Fe6(CH3O)4(NCO)4(CH3COO)2O2]∙2MeOH (5) were isolated through the reactions of N-(2-pyridylmethyl)iminodipropanol (H2pmidp) and iron(III) ions with different pseudohalide ions. The complexes were studied via X-ray crystal diffraction, Mössbauer spectra, and magnetochemistry. The molecular structures of 1 and 2 were formed as the {Fe2(µ2-Opropoxo)2}2+ cores with pmidp2− and NCSe−/NCBH3−. The structure of 3 was formed as a {Fe3(µ2-OCH3)2(µ2-Opropoxo)4}5+ core with Hpmidp−/pmidp2− and NCS−. The structures of 4 and 5 were formed as {Fe6(µ4-O)2(µ2-OCH3)2(η2-OAc)2(µ2-Opropoxo)4} cores with pmidp2− and NCO−/N3−. Structural analyses revealed that the formation of various multinuclear iron(III) moieties depends on the auxiliary ligands. The oxidation states of all the complexes were confirmed as + 3 using the bond valence sum (BVS) calculations and Mössbauer spectral data. The susceptibility data for 1–5 fitted using each spin coupling (J) model indicated that 1–3 showed antiferromagnetic exchange interactions, and 4 and 5 showed the ferromagnetic and antiferromagnetic couplings, simultaneously.

Distortion of the [FeNO]2 Core in Flavodiiron Nitric Oxide Reductase Models Inhibits N-N Bond Formation and Promotes Formation of Unusual Dinitrosyl Iron Complexes: Implications for Catalysis and Reactivity.

Flavodiiron nitric oxide reductases (FNORs) carry out the reduction of nitric oxide (NO) to nitrous oxide (N2O), allowing infectious pathogens to mitigate toxic levels of NO generated in the human immune response. We previously reported the model complex [Fe2(BPMP)(OPr)(NO)2](OTf)2 (1, OPr- = propionate) that contains two coplanar NO ligands and that is capable of quantitative NO reduction to N2O [White et al. J. Am. Chem. Soc. 2018, 140, 2562-2574]. Here we investigate, for the first time, how a distortion of the active site affects the ability of the diiron core to mediate N2O formation. For this purpose, we prepared several analogues of 1 that contain two monodentate ligands in place of the bridging carboxylate, [Fe2(BPMP)(X)2(NO)2]3+/1+ (2-X; X = triflate, 1-methylimidazole, or methanol). Structural data of 2-X show that without the bridging carboxylate, the diiron core expands, leading to elongated (O)N-N(O) distances (from 2.80 Å in 1 to 3.00-3.96 Å in 2-X) and distorted (O)N-Fe-Fe-N(O) dihedral angles (from coplanarity (5.9°) in 1 to 52.9-85.1° in 2-X). Whereas 1 produces quantitative amounts of N2O upon one-electron reduction, N2O production is substantially impeded in 2-X, to an initial 5-10% N2O yield. The main products after reduction are unprecedented hs-FeII/{Fe(NO)2}9/10 dinitrosyl iron complexes (DNICs). Even though mononuclear DNICs are stable and do not show N-N coupling (since it is a spin-forbidden process), the hs-FeII/{Fe(NO)2}9/10 DNICs obtained from 2-X show unexpected reactivity and produce up to quantitative N2O yields after 2 h. The implications of these results for the active site structure of FNORs are discussed.

Synergistic effects of iron and hexagonal-Boron Nitride additions in copper-based composites for braking application

This paper explores the addition of h-BN and iron to Cu-based brake pads on the performance benefits. It also investigates the effect of graded layering by synthesizing three and four-layer brake pads by powder compaction and sintering route. The top one or two layers are made of Cu-based composite containing Fe, h-BN, and W, while the middle layer is pure Cu and, bottom steel plate. Two different compositions were explored for the composites by varying Fe content. From the two composite compositions, brake pads with single-layer composite or two-layer composite were synthesized. Characterization of brake pad specimens was carried out using density measurements, optical microscopy, scanning electron microscopy, energy dispersive spectroscopy. The brake pads were subjected to simulated braking tests at braking energy/cycle of 60, 96, and 136 K Joules. Wear rate, coefficient of friction, stopping distance, stopping time, and hardness were measured and compared among other brake pads. The brake pad containing single-layer Fe rich Cu composite showed the best performance in the simulated braking tests. EDS analysis of wear debris shows the formation of iron (boride, nitride, oxide) complex which is indicative of a surface with superior dry lubricating properties. This surface is a result of synergetic interaction between h-BN and Fe particles. The iron particles which are scattered in the Cu matrix composite act as low friction regions on the brake pad surface that interrupt the high friction regions on the Cu matrix, thus reducing the local and bulk temperature rise. The two-layer composite brake-pad showed performance intermediate to the two single-layer brake pads. No advantage due to higher thermal conductivities in Fe deficient composite was observed as the two composite layers, showed similar Fe contents in their matrix phases.

Importance of High-Valent Iron Complex and Reactive Radicals in Organic Contaminants’ Abatement by the Fe-TAML/Free Chlorine System

This study demonstrated the formation of high-valent iron complex as well as free radicals in the reaction of iron(III)-tetraamidomacrocyclic ligand (FeIII-TAML) with free chlorine. FeIV(O)-TAML was generated at pH 5.0–10.0, while FeIV(O)-TAML can be further transformed into FeV(O)-TAML by free chlorine at pH 5.0–7.0. The one-electron reduction of free chlorine formed Cl•. The performance of the FeIII-TAML/free chlorine system toward organic contaminants was evaluated by investigating the degradation of three target organic contaminants with different functional groups. The pseudo-first-order rate constant (kobs) of organic contaminants’ degradation by the FeIII-TAML/free chlorine system was about 400–2000-fold greater than that by the FeIII-TAML/hydrogen peroxide (H2O2) system at pH 7.0. FeV(O)-TAML and FeIV(O)-TAML were proposed as the major high-valent iron oxidants responsible for organic contaminants’ degradation at pH 5.0–7.0 and at pH 8.0–10.0, respectively. Additionally, Cl• and secondary free radicals (e.g., Cl2•– and HO•) were responsible for organic contaminants’ degradation. The FeIII-TAML/free chlorine system might be a promising oxidation process because both selective oxidants (high-valent iron complex) and nonselective oxidants (free radicals) contribute to decomposition of organic contaminants in this process.

Comparative evaluation of in situ and ex-situ iron-complexing ability of exopolysaccharides producing lactic acid bacteria in whey medium

The present study investigated the iron-binding ability of exopolysaccharides (EPS) producing lactic acid bacteria (LAB) as a whole-cell in comparison with its extracted crude EPS. A total of eight EPS producing LAB strains and four iron salts were tested for in-situ iron complex formation in whey as a basal culture medium. Among the four iron salts, ferrous sulphate showed maximum complexation with all the LAB strains. Amongst eight EPS producing LAB strains, Lacticaseibacillus rhamnosus Kar1 showed significantly higher (P < 0.05) iron complexing ability in comparison with the other strains. In-situ iron chelating ability of EPS producing L. rhamnosus Kar1 strain was notably higher (65.5 ± 0.62%) than the ex-situ approach in whey (51.62 ± 0.89%) but was considerably lower than that observed in an aqueous medium (75.29 ± 0.824%). Under optimized conditions, L. rhamnosus Kar1 showed 81.20 ± 0.38% iron complex formation in whey supplemented with 11% glucose and 20 ppm iron (ferrous sulphate) at the fermentation duration of 14 h. These findings suggest that L. rhamnosus Kar1 and its EPS can be further explored to develop iron-fortified whey-based products upon amalgamation with suitable technology.