Binuclear Iron Complexes Research Articles

Neutral water-soluble µ-S nitrosyl iron complex with acetylcysteine non-silent in EPR spectra

The water-soluble neutral binuclear nitrosyl iron complex with N-acetyl-L-cysteine was synthesized. As follows from X-ray analysis, the complex crystallizes in the monoclinic crystal system, space group P2(1). The distance between iron atoms is 2.7 Å The complex belongs to Roussin's red salt esters (RRE) and is expected to be diamagnetic. However, in the EPR-spectrum there is a broad line with a g-factor of 2.010, which disappears upon the dissolution of the complex in water or alcohol. However, dissolution of the complex in DMSO leads to an increase in the classical signal for mononuclear nitrosyl iron complex with a g-factor of 2.03. The IR-spectrum of the crystalline sample of the complex shows an atypical pattern among RREs. This behaviour was studied with quantum-chemical calculations. The magnetic properties of the complex are also unusual for a complex of this structural type. The complex was also studied by Mössbauer and UV-spectroscopy.

Structure, properties, and decomposition in biological systems of a new nitrosyl iron complex with 2-methoxythiophenolyls, promising for the treatment of cardiovascular diseases

A new promising binuclear tetranitrosyl iron complex with 2-methoxythiophenolyl of the composition [Fe2(C7H7OS)2(NO)4] (complex 1), which acts on the therapeutic targets of cardiovascular diseases, guanylate and adenylate cyclase, has been synthesized. X-ray diffraction data show the presence of two isoforms of complex 1; according to quantum chemical calculations, the structure of only the trans isomer is stable in solutions.The processes of transformation of complex 1 in DMSO, in aqueous solutions, as well as in the presence of bovine serum albumin, reduced glutathione, and mucin were studied. DMSO promotes the decomposition of the original complex 1 into mononuclear products. In biological systems, the mechanisms of decomposition of the complex 1 differ from aqueous solutions. In albumin solution, a gradual formation of a high-molecular-weight dinitrosyl complex is observed, obtained by coordinating the [Fe(NO)2]+ fragment with the amino acid groups of the protein. In the presence of mucin, an EPR signal from stable mononitrosyl products is observed. The introduction of glutathione into the system of the complex 1 leads to the replacement of one initial thioligand with glutathione. In the model systems under study, a more efficient and prolonged generation of NO groups is observed compared to a buffer solution.The obtained data on the influence of the environment on the properties of the complex 1 in combination with a study of their effect on enzymes allow us to recommend it for further study as a potential drug with vasodilator, antianginal, and hypotensive properties.

Adducts of bovine serum albumin and binuclear nitrosyl iron complex with thiosulfate ligands: a molecular docking and quantum chemical study

Adducts of bovine serum albumin and binuclear nitrosyl iron complex with thiosulfate ligands: a molecular docking and quantum chemical study

Effect of Nitrosyl Iron Complex with 3,4-Dichlorothiophenolyls on the Level of Cyclic Nucleotide In Vitro.

The effect of a promising NO donor, a binuclear nitrosyl iron complex (NIC) with 3,4-dichlorothiophenolyls [Fe2(SC6H3Cl2)2(NO)4], on the adenylate cyclase and soluble guanylate cyclase enzymatic systems was studied. In in vitro experiments, this complex increased the concentration of important secondary messengers, such as cAMP and cGMP. An increase of their level by 2.4 and 4.5 times, respectively, was detected at NIC concentration of 0.1 mM. The ligand of the complex, 3,4-dichlorothiophenol, produced a less pronounced effect on adenylate cyclase. It was shown that the effect of this complex on the activity of soluble guanylate cyclase was comparable to the effect of anionic nitrosyl complex with thiosulfate ligands that exhibits vasodilating and cardioprotective properties.

Introducing Novel Redox-Active Bis(phenolate) N-Heterocyclic Carbene Proligands: Investigation of Their Coordination to Fe(II)/Fe(III) and Their Catalytic Activity in Transfer Hydrogenation of Carbonyl Compounds.

A simple and efficient procedure for synthesizing novel pincer-type tridentate N-heterocyclic carbene bisphenolate ligands is reported. The synthesis of pincer proligands with N,N'-disubstituted imidazoline core, 5 and 6, was carried out via triethylorthoformate-promoted cyclization of either N,N'-bis(2-hydroxy-3,5-di-tert-butylphenyl)cyclohexanediamine, 3, or N,N'-bis(2-hydroxyphenyl)cyclohexanediamine, 4, in the presence of concentrated hydrochloric acid. Cyclic voltammograms of the ligands revealed ligand-centered redox activity, indicating the noninnocent nature of the ligands. The voltammograms of the ligands exhibit two successive one-electron oxidations and two consecutive one-electron reductions. In contrast to previous reports, the redox-active ligands in this study exhibit one-electron oxidation and reduction processes. All products were thoroughly characterized by using 1H and 13C NMR spectroscopy. The base-promoted deprotonation of the proligands and subsequent reaction with iron(II) and iron(III) chlorides yielded compounds 7 and 8. These compounds are binuclear and tetranuclear iron(III) complexes that do not contain carbene functional groups. Complexes 7 and 8 were characterized by using elemental analysis and single-crystal X-ray crystallography. At low catalyst loadings, both 7 and 8 exhibited high catalytic activity in the transfer hydrogenation of selected aldehydes and ketones.

Binuclear nitrosyl iron complex with 4-acetamidothiophenolyl: Synthesis and study of its decomposition in a system with glutathione and albumin

In this work, we synthesized a new binuclear nitrosyl iron complex of the family of Roussin's red salt ester [Fe2(C8H8NOS)2(NO)4] (complex 1) with 4-acetamidothiophenol (a structural analog of acetaminophen), which generates NO during hydrolysis and is promising for treatment socially significant diseases. It has been established that solvents have a significant effect on the process of its decomposition: in a buffer solution, complex 1 retains its binuclear structure, while in DMSO it forms mononuclear iron-nitrosyl products. Reduced glutathione does not replace 4-acetamidothiophenol ligands in the structure of complex 1. In addition, complex 1 and its products are not coordinated with the known binding sites of bovine serum albumin, including Cys34. It was found that the studied complex 1 is adsorbed on the protein surface due to weak intermolecular interactions, which leads to a decrease in the rate of decomposition, and, as a result, to a longer generation of NO.Thus, it has been shown for the first time that compound 1 and its decay products do not form coordination complexes with the biosubstrates studied in this work. It can be assumed that glutathione will not participate in the transformation of complex 1 in vivo, while albumin, due to the effective stabilization of the complex on the surface, can act as its carrier to therapeutic targets.

Effect of F Substituents in Thiophenol on the Structure and Properties of µ2-S-(Difluorothiolate)tetranitrosyl Iron Binuclear Complexes

Two new neutral binuclear tetranitrosyl iron complexes of general formula [Fe2R2(NO)4] with R = 2,4-difluorothiophenyl (complex 1) and 3,4-difluorothiophenyl (complex 2), donors of nitrogen monoxide (NO), were prepared. The complexes were characterized by single-crystal X-ray diffraction, IR, Mössbauer, EPR spectroscopy, and elemental analysis. The antibacterial activity and cytotoxicity of complex 1, complex 2, and previously synthesized [(NO)4] with R'= 2,4-dichlorothiophenyl (complex 3) were studied for the first time. The “amount of NO–biological activity” correlations were analyzed depending on the nature and position of the substituent in the thiophenyl ligand. Complex 2 was found to have antibacterial activity that was four times as high as that of the known antibiotic kanamycin. The anti-biofilm activity of complex 2 was studied; it inhibited 46% of biofilm formation and destroyed 32% of M. Luteus biofilms, surpassing the effects of the reference drugs kanamycin and ampicillin.

Dinitrosyl iron complexes with thiol-containing ligands as sources of universal cytotoxins - nitrosonium cations

It was shown that the release of a half of nitrosyl ligands from dinitrosyl iron units in the form of nitrosonium cation (NO+) from binuclear dinitrosyl iron complexes with thiol-containing ligands (B-DNIC) during DNIC decomposition in acid solutions is increased with the decrease of the stability of these complexes and completely blocked with the increase of the concentrations of free thiols (non-included into B-DNIC) up to the level that was two times and more than that of dinitrosyl iron units. It was demonstrated that the less stable B-DNIC with mercaptosuccinate degrade in an acidic environment at ambient temperature, while the decomposition of more stable B-DNIC with glutathione was only marked when the solution was heated at 80°C. The inhibition of NO+ release from B-DNIC in the presence of elevated free thiol level in the solution was due to the ability of free thiols to induce the reduction of NO+ to NO.

ELECTRON TRANSFER REACTIONS OF BRIDGED BINUCLEAR IRON(III)- COMPLEXES: A REVIEW

Binuclear iron (III) complexes comprising of the -oxo-bridged form, [Fe2O]4+ or [Fe(OH)2]4+, and the dicarboxylic bridged chains incorporating salen or saloph ligands have been synthesized and characterized. Their close resemblance to some haeme and non-haeme iron-based enzymes has elicited a lot of interest in studying them. Biological studies have shown some of them to be good mimics of superoxide dismutase. The saloph and salen analogues also showed physiological actions very close to the porphyrins. The study of their electron transfer reactions, with a view of understanding their potential as electron transfer enzymes, has generated interesting results and some unusual kinetic behaviours. Reactions of [(FeHEDTA)2O]2+ with ascorbic acid and some thiols were second order and followed outer-sphere path mediated by ion-pairs formation. However, reaction of [Fe2(bipy)O]4+ with some reductants were zero order with respect to the oxidant and also followed outer-sphere path. Reduction of the adipato-bridged dimer, [Fe(saloph)2µ-adi], by SO32- and SO42-, S2O52-, benzyl mercaptan, mercaptobenzothiazole and thioglycolic acid followed inner-sphere paths. However, all the reactions were acid-catalysed and were mediated by intervening protonated oxidant precursor complexes.

Beneficial Effects of Dinitrosyl Iron Complexes on Wound Healing Compared to Commercial Nitric Oxide Plasma Generator.

Nitric oxide (NO) is a gaseous molecule which plays a key role in wound healing. Previously, we identified the optimal conditions for wound healing strategies using NO donors and an air plasma generator. The aim of this study was to compare the wound healing effects of binuclear dinitrosyl iron complexes with glutathione (B-DNIC-GSH) and NO-containing gas flow (NO-CGF) at their optimal NO doses (0.04 mmol for B-DNIC-GSH and 1.0 mmol for NO-CGF per 1 cm2) in a rat full-thickness wound model over a 3-week period. Excised wound tissues were studied by light and transmission electron microscopy and immunohistochemical, morphometrical and statistical methods. Both treatments had an identical stimulating impact on wound healing, which indicated a higher dosage effectiveness of B-DNIC-GSH compared to the NO-CGF. B-DNIC-GSH spray application reduced inflammation and promoted fibroblast proliferation, angiogenesis and the growth of granulation tissue during the first 4 days after injury. However, prolonged NO spray effects were mild compared to NO-CGF. Future studies should determine the optimal B-DNIC-GSH solution course for a more effective wound healing stimulation.

Magnetic response of photonic crystals based on nucleating agents of binuclear complexes

In the synthesis of Fe3O4 MRPCs via the solvothermal reduction route, The formation of a binuclear iron complex involving both Fe2+ and Fe3+ is key to imparting the product with monodispersity, superparamagnetism and magnetochromatic properties.

The Influence of Cationic Nitrosyl Iron Complex with Penicillamine Ligands on Model Membranes, Membrane-Bound Enzymes and Lipid Peroxidation.

This paper shows the biological effects of cationic binuclear tetranitrosyl iron complex with penicillamine ligands (TNIC-PA). Interaction with a model membrane was assessed using a fluorescent probes technique. Antioxidant activity was studied using a thiobarbituric acid reactive species assay (TBARS) and a chemiluminescence assay. The catalytic activity of monoamine oxidase (MAO) was determined by measuring liberation of ammonia. Antiglycation activity was determined fluometrically by thermal glycation of albumine by D-glucose. The higher values of Stern-Volmer constants (KSV) obtained for the pyrene located in hydrophobic regions (3.9 × 104 M-1) compared to KSV obtained for eosin Y located in the polar headgroup region (0.9 × 104 M-1) confirms that TNIC-PA molecules prefer to be located in the hydrophobic acyl chain region, close to the glycerol group of lipid molecules. TNIC-PA effectively inhibited the process of spontaneous lipid peroxidation, due to additive contributions from releasing NO and penicillamine ligand (IC50 = 21.4 µM) and quenched luminol chemiluminescence (IC50 = 3.6 μM). High activity of TNIC-PA in both tests allows us to assume a significant role of its radical-scavenging activity in the realization of antioxidant activity. It was shown that TNIC-PA (50-1000 μM) selectively inhibits the membrane-bound enzyme MAO-A, a major source of ROS in the heart. In addition, TNIC-PA is an effective inhibitor of non-enzymatic protein glycation. Thus, the evaluated biological effects of TNIC-PA open up the possibility of its practical application in chemotherapy for socially significant diseases, especially cardiovascular diseases.

Antiviral Activity of Nitrosonium Cations against SARS-CoV-2 on a Syrian Hamster Model

The antiviral action of binuclear dinitrosyl iron complexes with glutathione along with diethyldithiocarbamate against the SARS-CoV-2 virus has been demonstrated on a Syrian hamster model after aerosol exposure of SARS-CoV-2-infected animals to the solutions of said compounds. EPR assays in analogous experiments on intact hamsters have demonstrated that the iron complexes and diethyldithiocarbamate are predominantly localized in lung tissues. These results have been compared with similar measurements on intact mice, which have shown the equal localization of these agents in both the lungs and liver. We assume that the release of the nitrosonium cations from the binuclear dinitrosyl iron complexes with glutathione occurs during their contact with diethyldithiocarbamate in the animal body. These cations caused S-nitrosation of host and viral cell proteases, leading to suppression of SARS-CoV-2 infection.

The Cytostatic Action of Dinitrosyl Iron Complexes with Glutathione on Escherichia coli Cells Is Mediated by Nitrosonium Cations Released from These Complexes.

This study demonstrates a bacteriostatic effect of binuclear dinitrosyl iron complexes with glutathione on Escherichia coli TN300 cells. It has been quantified by the colony formation assay. The bacteriostatic effect exerted by these complexes increases considerably in the presence of diethyldithiocarbamate. Our results suggest that this effect is caused by the intense release of nitrosonium cations, NO+, from the complexes, which decompose under the action of diethyldithiocarbamate. A similar effect is observed when E.coli cells are treated with diethyldithiocarbamate 40 min after the addition of sodium nitrite or S-nitrosoglutathione. Notably, the level of dinitrosyl iron complexes observed in the bacterial cells due to the effects of sodium nitrite or S-nitrosoglutathione is almost the same as that obtained after treatment with glutathione-containing complexes. The bacteriostatic effects of the NO molecules released from nitrite or S-nitrosoglutathione during their brief interaction with bacteria were significantly smaller than the bacteriostatic effect of NO+. Wededuce therefrom that the nitrosonium cations released from DNICs are responsible for the observed bacteriostatic effect of these complexes in E. coli cells.

Magnetic exchange interactions in binuclear and tetranuclear iron(III) complexes described by spin-flip DFT and Heisenberg effective Hamiltonians.

Low-energy spectra of single-molecule magnets (SMMs) are often described by Heisenberg Hamiltonians. Within this formalism, exchange interactions between magnetic centers determine the ground-state multiplicity and energy separation between the ground and excited states. In this contribution, we extract exchange coupling constants (J) for a set of iron (III) binuclear and tetranuclear complexes from all-electron calculations using non-collinear spin-flip time-dependent density functional theory (NC-SF-TDDFT). For 12 binuclear complexes with J-values ranging from -6 to -132 cm-1 , our benchmark calculations using the short-range hybrid ωPBEh functional and 6-31G(d,p) basis set agree well with the experimentally derived values (mean absolute error of 4.7cm-1 ). For the tetranuclear SMMs, the computed J constants are within 6cm-1 from the experimentally derived values. We explore the range of applicability of the Heisenberg model by analyzing bonding patterns in these Fe(III) complexes using natural orbitals (NO), their occupations, and the number of effectively unpaired electrons. The results illustrate the efficiency of the spin-flip protocol for computing the exchange couplings and the utility of the NO analysis in assessing the validity of effective spin Hamiltonians.

A mono-oxo-bridged binuclear iron(iii) complex with a Fe–O–Fe angle of 180.0° and its catalytic activity for hydrogen evolution

There are potential applications for binuclear oxo-bridged iron complexes in biological processes, catalysts, and magnetic materials, and the design of new bridged-iron complexes is important.

Reactions of water-soluble binuclear tetranitrosyl iron complexes of the μ-S structural type with adenosine triphosphoric acid: Kinetics and reaction mechanism

The reactions of adenosine triphosphoric acid (ATP) with water-soluble binuclear tetranitrosyl iron complexes of the μ-S structural type with functional sulfur-containing ligands (thiosulfate (1) cysteamine (2), and penicillamine (3)) afford products of close structures. The hydrolysis products of the complexes (1–3) in aqueous aerobic solutions are studied by amperometry and mass electrospectrometry. The kinetic regularities of the reactions of the complexes (1–3) with ATP are studied by the spectrofluorimetric method. A generalized kinetic model describing the experimental data of three reactions is proposed for the process. From the qualitative point of view, the reactions of ATP with the studied complexes occur similarly in spite of the difference in the ligands. The rates of particular steps of the process depend on the nature of the ligands. The values determined for the kinetic parameters quantitatively characterize the influence of the ligand nature in complexes 1–3 on the reactivity toward ATP and increase in the order: cysteamine < penicillamine < thiosulfate.

Iron‐Iron Bond Lengths and Bond Orders in Diiron Lantern‐Type Complexes with High Spin Ground States

AbstractDiiron paddlewheel‐ or lantern‐type complexes comprise an interesting subclass of binuclear iron complexes, existing with digonal, trigonal, and tetragonal ligand arrays. Experimentally known members show Fe−Fe bonds of lengths ranging from 2.13 to 2.73 Å, with Fe−Fe bond orders ranging from 0.5 to 2. Truncated models for 30 experimentally characterized diiron paddlewheel‐type complexes have been studied by DFT using the M06‐L functional, reproducing the Fe−Fe bond lengths quite well. In addition, we use DFT to treat three series of model diiron complexes Fe2Lx (x=2, 3, 4) in various low‐lying spin states, L being the unsubstituted formamidinate, guanidinate, and formate ligands (along with a series of axially ligated formate complexes) in order to predict ground state spin multiplicities, Fe−Fe bond lengths, and features of the ligand arrays. The ground states all have high spin multiplicities (septets, octets, and nonets). Formal bond order (fBO) values are suggested for the Fe−Fe bonds in these 61 complexes using an electron bookkeeping procedure, in addition to the Fe−Fe bond orders obtained by metal‐metal MO analysis for ground state species. Fe−Fe bond orders up to 3 are noted in some excited states. Deviations from D3h and D4h symmetry are noted for many trigonal and tetragonal complexes, being attributed to inherent Jahn‐Teller distortions. The formamidinate and guanidinate series show many similarities, while the formate series differs from these two in several aspects. From these results, ranges are derived for Fe−Fe bond lengths of orders 0.5, 1.0, 1.5, 2.0, 2.5 and 3.0. The Fe−Fe bond length ranges for these non‐carbonyl lantern complexes are found to be appreciably lower than the corresponding ranges for diiron complexes with carbonyl ligands as compiled earlier from computational and experimental results.

Nitrosonium Cation as a Cytotoxic Component of Dinitrosyl Iron Complexes with Thiol-containing Ligands (based on the Experimental Work on MCF7 Human Breast Cancer Cell Culture).

Here we demonstrate that binuclear dinitrosyl iron complexes with thiol-containing ligands (glutathione and mercaptosuccinate, B-DNIC-GSH and B-DNIC-MS, respectively) exert cytotoxic effects on MCF7 human breast cancer cells. We showed that they are mediated by nitrosonium cations released from these complexes (NO+). This finding is supported by the cytotoxic effect of both B-DNICs on MCF7 cells evidenced to retain or was even promoted in the presence of N-Methyl-D-glucamine dithiocarbamate (MGD). MGD recruits an iron nitrosyl group [Fe(NO)] from the iron-dinitrosyl fragment [Fe(NO)2] of B-DNIC-MS forming stable mononitrosyl complexes of iron with MGD and releasing NO+ cations from a [Fe(NO)2] fragment.

Structure, nitric oxide (NO) generation and antitumor activity of binuclear tetranitrosyl iron complex with 4-aminothiophenolyl as nitrosyl ferredoxins mimic

Single-crystal XRD structure of binuclear tetranitrosyliron complex [Fe2(SR)2(NO)4] (1), R = 4-aminothiophenyl, has been described. The properties of 1 were studied by IR, Mössbauer, mass spectroscopy, and amperometry. Complex 1 was shown to form long-living nitrosyl intermediates in solution, which underlies its prolonged NO donor activity. In HeLa cells, 1 caused accumulation of NF-κB p50 but decreased the levels of NF-κB p65 in the nucleus, which led to inhibition of NF-κB dependent genes. The complex also induced increase of p53 protein levels and p21 gene activity, which led to the apoptotic cell death after G2/M cell cycle phase.